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CNS & Neurological Disorders - Drug Targets

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ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

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Review Article

Stroke and Vascular Cognitive Impairment: The Role of Intestinal Microbiota Metabolite TMAO

Author(s): Ruxin Tu and Jian Xia*

Volume 23, Issue 1, 2024

Published on: 08 March, 2023

Page: [102 - 121] Pages: 20

DOI: 10.2174/1871527322666230203140805

Price: $65

Abstract

The gut microbiome interacts with the brain bidirectionally through the microbiome-gutbrain axis, which plays a key role in regulating various nervous system pathophysiological processes. Trimethylamine N-oxide (TMAO) is produced by choline metabolism through intestinal microorganisms, which can cross the blood-brain barrier to act on the central nervous system. Previous studies have shown that elevated plasma TMAO concentrations increase the risk of major adverse cardiovascular events, but there are few studies on TMAO in cerebrovascular disease and vascular cognitive impairment. This review summarized a decade of research on the impact of TMAO on stroke and related cognitive impairment, with particular attention to the effects on vascular cognitive disorders. We demonstrated that TMAO has a marked impact on the occurrence, development, and prognosis of stroke by regulating cholesterol metabolism, foam cell formation, platelet hyperresponsiveness and thrombosis, and promoting inflammation and oxidative stress. TMAO can also influence the cognitive impairment caused by Alzheimer's disease and Parkinson's disease via inducing abnormal aggregation of key proteins, affecting inflammation and thrombosis. However, although clinical studies have confirmed the association between the microbiome-gut-brain axis and vascular cognitive impairment (cerebral small vessel disease and post-stroke cognitive impairment), the molecular mechanism of TMAO has not been clarified, and TMAO precursors seem to play the opposite role in the process of poststroke cognitive impairment. In addition, several studies have also reported the possible neuroprotective effects of TMAO. Existing therapies for these diseases targeted to regulate intestinal flora and its metabolites have shown good efficacy. TMAO is probably a new target for early prediction and treatment of stroke and vascular cognitive impairment.

Keywords: Gut microbiome, TMAO, stroke, vascular cognitive impairment, post-stroke cognitive impairment, dementia.

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[1]
Benakis C, Martin-Gallausiaux C, Trezzi JP, Melton P, Liesz A, Wilmes P. The microbiome-gut-brain axis in acute and chronic brain diseases. Curr Opin Neurobiol 2020; 61: 1-9.
[http://dx.doi.org/10.1016/j.conb.2019.11.009] [PMID: 31812830]
[2]
Cryan JF, O’Riordan KJ, Sandhu K, Peterson V, Dinan TG. The gut microbiome in neurological disorders. Lancet Neurol 2020; 19(2): 179-94.
[http://dx.doi.org/10.1016/S1474-4422(19)30356-4] [PMID: 31753762]
[3]
Smith LK, Wissel EF. Microbes and the mind: How bacteria shape affect, neurological processes, cognition, social relationships, development, and pathology. Perspect Psychol Sci 2019; 14(3): 397-418.
[http://dx.doi.org/10.1177/1745691618809379] [PMID: 30920916]
[4]
Generoso JS, Giridharan VV, Lee J, Macedo D, Barichello T. The role of the microbiota-gut-brain axis in neuropsychiatric disorders. Br J Psychiatry 2021; 43(3): 293-305.
[http://dx.doi.org/10.1590/1516-4446-2020-0987] [PMID: 32667590]
[5]
Simeonova D, Stoyanov D, Leunis JC, et al. Increased serum immunoglobulin responses to gut commensal gram-negative bacteria in unipolar major depression and bipolar disorder type 1, especially when melancholia is present. Neurotox Res 2020; 37(2): 338-48.
[http://dx.doi.org/10.1007/s12640-019-00126-7] [PMID: 31802379]
[6]
Maes M, Simeonova D, Stoyanov D, Leunis JC. Upregulation of the nitrosylome in bipolar disorder type 1 (BP1) and major depression, but not BP2: Increased IgM antibodies to nitrosylated conjugates are associated with indicants of leaky gut. Nitric Oxide 2019; 91: 67-76.
[http://dx.doi.org/10.1016/j.niox.2019.07.003] [PMID: 31323278]
[7]
Strandwitz P. Neurotransmitter modulation by the gut microbiota Brain Research 2018; 1693(Pt B): 128-33.
[http://dx.doi.org/10.1016/j.brainres.2018.03.015]
[8]
Zhu S, Jiang Y, Xu K, et al. The progress of gut microbiome research related to brain disorders. J Neuroinflammation 2020; 17(1): 25.
[http://dx.doi.org/10.1186/s12974-020-1705-z] [PMID: 31952509]
[9]
Mörkl S, Butler MI, Holl A, Cryan JF, Dinan TG. Probiotics and the microbiota-gut-brain axis: focus on psychiatry. Curr Nutr Rep 2020; 9(3): 171-82.
[http://dx.doi.org/10.1007/s13668-020-00313-5] [PMID: 32406013]
[10]
Gong L, Wang H, Dong Q, et al. Intracranial atherosclerotic stenosis is related to post-stroke cognitive impairment: a cross-sectional study of minor stroke. Curr Alzheimer Res 2020; 17(2): 177-84.
[http://dx.doi.org/10.2174/1567205017666200303141920] [PMID: 32124696]
[11]
Jokinen H, Melkas S, Ylikoski R, et al. Post-stroke cognitive impairment is common even after successful clinical recovery. Eur J Neurol 2015; 22(9): 1288-94.
[http://dx.doi.org/10.1111/ene.12743] [PMID: 26040251]
[12]
Janeiro M, Ramírez M, Milagro F, Martínez J, Solas M. Implication of Trimethylamine N-Oxide (TMAO) in disease: potential biomarker or new therapeutic target. Nutrients 2018; 10(10): 1398.
[http://dx.doi.org/10.3390/nu10101398] [PMID: 30275434]
[13]
Chen Y, Zhou J, Wang L. Role and mechanism of gut microbiota in human disease. Front Cell Infect Microbiol 2021; 11: 625913.
[http://dx.doi.org/10.3389/fcimb.2021.625913] [PMID: 33816335]
[14]
Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol 2021; 19(1): 55-71.
[http://dx.doi.org/10.1038/s41579-020-0433-9] [PMID: 32887946]
[15]
Koszewicz M, Jaroch J, Brzecka A, et al. Dysbiosis is one of the risk factor for stroke and cognitive impairment and potential target for treatment. Pharmacol Res 2021; 164: 105277.
[http://dx.doi.org/10.1016/j.phrs.2020.105277] [PMID: 33166735]
[16]
Zhu W, Romano KA, Li L, et al. Gut microbes impact stroke severity via the trimethylamine N-oxide pathway. Cell Host Microbe 2021; 29(7): 1199-1208.e5.
[http://dx.doi.org/10.1016/j.chom.2021.05.002] [PMID: 34139173]
[17]
Nam HS. Gut microbiota and ischemic stroke: the role of trimethylamine N-Oxide. J Stroke 2019; 21(2): 151-9.
[http://dx.doi.org/10.5853/jos.2019.00472] [PMID: 31161760]
[18]
Pluta R, Januszewski S, Czuczwar SJ. The role of gut microbiota in an ischemic stroke. Int J Mol Sci 2021; 22(2): 915.
[http://dx.doi.org/10.3390/ijms22020915] [PMID: 33477609]
[19]
Velasquez M, Ramezani A, Manal A, Raj D. Trimethylamine n-oxide: the good, the bad and the unknown. Toxins 2016; 8(11): 326.
[http://dx.doi.org/10.3390/toxins8110326] [PMID: 27834801]
[20]
Romano KA, Vivas EI, Amador-Noguez D, Rey FE. Intestinal microbiota composition modulates choline bioavailability from diet and accumulation of the proatherogenic metabolite trimethylamine-N-oxide. MBio 2015; 6(2): e02481-14.
[http://dx.doi.org/10.1128/mBio.02481-14] [PMID: 25784704]
[21]
Wang Z, Levison BS, Hazen JE, Donahue L, Li XM, Hazen SL. Measurement of trimethylamine-N-oxide by stable isotope dilution liquid chromatography tandem mass spectrometry. Anal Biochem 2014; 455: 35-40.
[http://dx.doi.org/10.1016/j.ab.2014.03.016] [PMID: 24704102]
[22]
Boutagy NE, Neilson AP, Osterberg KL, et al. Short-term high-fat diet increases postprandial trimethylamine- N -oxide in humans. Nutr Res 2015; 35(10): 858-64.
[http://dx.doi.org/10.1016/j.nutres.2015.07.002] [PMID: 26265295]
[23]
Mafra D, Borges NA, Cardozo LFMF, et al. Red meat intake in chronic kidney disease patients: Two sides of the coin. Nutrition 2018; 46: 26-32.
[http://dx.doi.org/10.1016/j.nut.2017.08.015] [PMID: 29290351]
[24]
Wang Z, Klipfell E, Bennett BJ, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011; 472(7341): 57-63.
[http://dx.doi.org/10.1038/nature09922] [PMID: 21475195]
[25]
Ke Y, Li D, Zhao M, et al. Gut flora-dependent metabolite Trimethylamine-N-oxide accelerates endothelial cell senescence and vascular aging through oxidative stress. Free Radic Biol Med 2018; 116: 88-100.
[http://dx.doi.org/10.1016/j.freeradbiomed.2018.01.007] [PMID: 29325896]
[26]
Naghipour S, Cox AJ, Peart JN, Du Toit EF, Headrick JP. Trimethylamine N -oxide: heart of the microbiota–CVD nexus? Nutr Res Rev 2021; 34(1): 125-46.
[http://dx.doi.org/10.1017/S0954422420000177] [PMID: 32718365]
[27]
Fu Q, Zhao M, Wang D, et al. Coronary plaque characterization assessed by optical coherence tomography and plasma trimethylamine-n-oxide levels in patients with coronary artery disease. Am J Cardiol 2016; 118(9): 1311-5.
[http://dx.doi.org/10.1016/j.amjcard.2016.07.071] [PMID: 27600460]
[28]
Svingen GFT, Zuo H, Ueland PM, et al. Increased plasma trimethylamine- N -oxide is associated with incident atrial fibrillation. Int J Cardiol 2018; 267: 100-6.
[http://dx.doi.org/10.1016/j.ijcard.2018.04.128] [PMID: 29957250]
[29]
Suzuki T, Heaney LM, Bhandari SS, Jones DJL, Ng LL. Trimethylamine N -oxide and prognosis in acute heart failure. Heart 2016; 102(11): 841-8.
[http://dx.doi.org/10.1136/heartjnl-2015-308826] [PMID: 26869641]
[30]
Lee Y, Nemet I, Wang Z, et al. Longitudinal plasma measures of trimethylamine n-oxide and risk of atherosclerotic cardiovascular disease events in community-based older adults. J Am Heart Assoc 2021; 10(17): e020646.
[http://dx.doi.org/10.1161/JAHA.120.020646] [PMID: 34398665]
[31]
Matsuzawa Y, Guddeti RR, Kwon TG, Lerman LO, Lerman A. Treating coronary disease and the impact of endothelial dysfunction. Prog Cardiovasc Dis 2015; 57(5): 431-42.
[http://dx.doi.org/10.1016/j.pcad.2014.10.004] [PMID: 25459974]
[32]
Tang WHW, Wang Z, Li XS, et al. Increased trimethylamine n-oxide portends high mortality risk independent of glycemic control in patients with type 2 diabetes mellitus. Clin Chem 2017; 63(1): 297-306.
[http://dx.doi.org/10.1373/clinchem.2016.263640] [PMID: 27864387]
[33]
Missailidis C, Hällqvist J, Qureshi AR, et al. Serum trimethylamine-n-oxide is strongly related to renal function and predicts outcome in chronic kidney disease. PLoS One 2016; 11(1): e0141738.
[http://dx.doi.org/10.1371/journal.pone.0141738] [PMID: 26751065]
[34]
Xu KY, Xia GH, Lu JQ, et al. Impaired renal function and dysbiosis of gut microbiota contribute to increased trimethylamine-N-oxide in chronic kidney disease patients. Sci Rep 2017; 7(1): 1445.
[http://dx.doi.org/10.1038/s41598-017-01387-y] [PMID: 28469156]
[35]
Senthong V, Wang Z, Fan Y, Wu Y, Hazen SL, Tang WHW. Trimethylamine n -oxide and mortality risk in patients with peripheral artery disease. J Am Heart Assoc 2016; 5(10): e004237.
[http://dx.doi.org/10.1161/JAHA.116.004237] [PMID: 27792653]
[36]
Komaroff AL. The microbiome and risk for atherosclerosis. JAMA 2018; 319(23): 2381-2.
[http://dx.doi.org/10.1001/jama.2018.5240] [PMID: 29800043]
[37]
Zeisel SH, Warrier M. Trimethylamine n -oxide, the microbiome, and heart and kidney disease. Annu Rev Nutr 2017; 37(1): 157-81.
[http://dx.doi.org/10.1146/annurev-nutr-071816-064732] [PMID: 28715991]
[38]
Obermeier B, Daneman R, Ransohoff RM. Development, maintenance and disruption of the blood-brain barrier. Nat Med 2013; 19(12): 1584-96.
[http://dx.doi.org/10.1038/nm.3407] [PMID: 24309662]
[39]
Brunt VE, LaRocca TJ, Bazzoni AE, et al. The gut microbiome–derived metabolite trimethylamine N-oxide modulates neuroinflammation and cognitive function with aging. Geroscience 2021; 43(1): 377-94.
[http://dx.doi.org/10.1007/s11357-020-00257-2] [PMID: 32862276]
[40]
Enko D, Zelzer S, Niedrist T, et al. Assessment of trimethylamine-N-oxide at the blood-cerebrospinal fluid barrier: Results from 290 lumbar punctures. EXCLI J 2020; 19: 1275-81.
[http://dx.doi.org/10.17179/excli2020-2763] [PMID: 33122976]
[41]
Villalobos ARA, Renfro JL. Trimethylamine oxide suppresses stress-induced alteration of organic anion transport in choroid plexus. J Exp Biol 2007; 210(3): 541-52.
[http://dx.doi.org/10.1242/jeb.02681] [PMID: 17234624]
[42]
Hernandez L, Ward LJ, Arefin S, et al. Blood–brain barrier and gut barrier dysfunction in chronic kidney disease with a focus on circulating biomarkers and tight junction proteins. Sci Rep 2022; 12(1): 4414.
[http://dx.doi.org/10.1038/s41598-022-08387-7] [PMID: 35292710]
[43]
Hoyles L, Pontifex MG, Rodriguez-Ramiro I, et al. Regulation of blood–brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide. Microbiome 2021; 9(1): 235.
[http://dx.doi.org/10.1186/s40168-021-01181-z] [PMID: 34836554]
[44]
Mudimela S, Vishwanath NK, Pillai A, et al. Clinical significance and potential role of trimethylamine N-oxide in neurological and neuropsychiatric disorders. Drug Discov Today 2022; 27(11): 103334.
[http://dx.doi.org/10.1016/j.drudis.2022.08.002] [PMID: 35998800]
[45]
Feigin VL, Stark BA, Johnson CO, et al. Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol 2021; 20(10): 795-820.
[http://dx.doi.org/10.1016/S1474-4422(21)00252-0] [PMID: 34487721]
[46]
Wu S, Wu B, Liu M, et al. Stroke in China: advances and challenges in epidemiology, prevention, and management. Lancet Neurol 2019; 18(4): 394-405.
[http://dx.doi.org/10.1016/S1474-4422(18)30500-3] [PMID: 30878104]
[47]
Hu W, Kong X, Wang H, Li Y, Luo Y. Ischemic stroke and intestinal flora: an insight into brain–gut axis. Eur J Med Res 2022; 27(1): 73.
[http://dx.doi.org/10.1186/s40001-022-00691-2] [PMID: 35614480]
[48]
Singh V, Roth S, Llovera G, et al. Microbiota dysbiosis controls the neuroinflammatory response after stroke. J Neurosci 2016; 36(28): 7428-40.
[http://dx.doi.org/10.1523/JNEUROSCI.1114-16.2016] [PMID: 27413153]
[49]
Peh A, O’Donnell JA, Broughton BRS, Marques FZ. Gut microbiota and their metabolites in stroke: a double-edged sword. Stroke 2022; 53(5): 1788-801.
[http://dx.doi.org/10.1161/STROKEAHA.121.036800] [PMID: 35135325]
[50]
Schneider C, Okun JG, Schwarz KV, et al. Trimethylamine-N-oxide is elevated in the acute phase after ischaemic stroke and decreases within the first days. Eur J Neurol 2020; 27(8): 1596-603.
[http://dx.doi.org/10.1111/ene.14253] [PMID: 32282978]
[51]
Tan C, Wang H, Gao X, et al. Dynamic changes and prognostic value of gut microbiota-dependent trimethylamine-n-oxide in acute ischemic stroke. Front Neurol 2020; 11: 29.
[http://dx.doi.org/10.3389/fneur.2020.00029] [PMID: 32082246]
[52]
Yin J, Liao SX, He Y, et al. Dysbiosis of gut microbiota with reduced trimethylamine-n-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack. J Am Heart Assoc 2015; 4(11): e002699.
[http://dx.doi.org/10.1161/JAHA.115.002699] [PMID: 26597155]
[53]
Manolis AA, Manolis TA, Melita H, Manolis AS. Gut microbiota and cardiovascular disease: symbiosis versus dysbiosis. Curr Med Chem 2022; 29(23): 4050-77.
[http://dx.doi.org/10.2174/0929867328666211213112949] [PMID: 34961453]
[54]
Chen YY, Ye ZS, Xia NG, Xu Y. TMAO as a novel predictor of major adverse vascular events and recurrence in patients with large artery atherosclerotic ischemic stroke. Clin Appl Thromb Hemost 2022; 28.
[http://dx.doi.org/10.1177/10760296221090503] [PMID: 35345908]
[55]
Farhangi MA, Vajdi M, Asghari-Jafarabadi M. Gut microbiota-associated metabolite trimethylamine N-Oxide and the risk of stroke: a systematic review and dose–response meta-analysis. Nutr J 2020; 19(1): 76.
[http://dx.doi.org/10.1186/s12937-020-00592-2] [PMID: 32731904]
[56]
Wu C, Xue F, Lian Y, et al. Relationship between elevated plasma trimethylamine N-oxide levels and increased stroke injury. Neurology 2020; 94(7): e667-77.
[http://dx.doi.org/10.1212/WNL.0000000000008862] [PMID: 31907287]
[57]
Zhang J, Wang L, Cai J, et al. Gut microbial metabolite TMAO portends prognosis in acute ischemic stroke. J Neuroimmunol 2021; 354: 577526.
[http://dx.doi.org/10.1016/j.jneuroim.2021.577526] [PMID: 33647820]
[58]
Rexidamu M, Li H, Jin H, Huang J. Serum levels of Trimethylamine-N-oxide in patients with ischemic stroke. Biosci Rep 2019; 39(6): BSR20190515.
[http://dx.doi.org/10.1042/BSR20190515] [PMID: 31142624]
[59]
Liang Z, Dong Z, Guo M, et al. Trimethylamine N-oxide as a risk marker for ischemic stroke in patients with atrial fibrillation. J Biochem Mol Toxicol 2019; 33(2): e22246.
[http://dx.doi.org/10.1002/jbt.22246] [PMID: 30370581]
[60]
Liu D, Gu S, Zhou Z, Ma Z, Zuo H. Associations of plasma TMAO and its precursors with stroke risk in the general population: A nested case-control study. J Intern Med 2023; 293(1): 110-20.
[http://dx.doi.org/10.1111/joim.13572] [PMID: 36200542]
[61]
Sun T, Zhang Y, Yin J, et al. Association of gut microbiota-dependent metabolite trimethylamine n-oxide with first ischemic stroke. J Atheroscler Thromb 2021; 28(4): 320-8.
[http://dx.doi.org/10.5551/jat.55962] [PMID: 32641646]
[62]
Nie J, Xie L, Zhao B, et al. Serum trimethylamine n-oxide concentration is positively associated with first stroke in hypertensive patients. Stroke 2018; 49(9): 2021-8.
[http://dx.doi.org/10.1161/STROKEAHA.118.021997] [PMID: 30354996]
[63]
Xu J, Cheng A, Song B, et al. Trimethylamine n-oxide and stroke recurrence depends on ischemic stroke subtypes. Stroke 2022; 53(4): 1207-15.
[http://dx.doi.org/10.1161/STROKEAHA.120.031443] [PMID: 34794334]
[64]
Xu K, Gao X, Xia G, et al. Rapid gut dysbiosis induced by stroke exacerbates brain infarction in turn. Gut 2021; 70(8): 1486-94.
[http://dx.doi.org/10.1136/gutjnl-2020-323263] [PMID: 33558272]
[65]
Wu C, Li C, Zhao W, et al. Elevated trimethylamine N -oxide related to ischemic brain lesions after carotid artery stenting. Neurology 2018; 90(15): e1283-90.
[http://dx.doi.org/10.1212/WNL.0000000000005298] [PMID: 29540587]
[66]
Randrianarisoa E, Lehn-Stefan A, Wang X, et al. Relationship of Serum Trimethylamine N-Oxide (TMAO) Levels with early Atherosclerosis in Humans. Sci Rep 2016; 6(1): 26745.
[http://dx.doi.org/10.1038/srep26745] [PMID: 27228955]
[67]
Wang B, Qiu J, Lian J, Yang X, Zhou J. Gut metabolite trimethylamine-n-oxide in atherosclerosis: from mechanism to therapy. Front Cardiovasc Med 2021; 8: 723886.
[http://dx.doi.org/10.3389/fcvm.2021.723886] [PMID: 34888358]
[68]
Krüger-Genge A, Jung F, Hufert F, Jung EM, Küpper JH, Storsberg J. Effects of gut microbial metabolite trimethylamine N-oxide (TMAO) on platelets and endothelial cells. Clin Hemorheol Microcirc 2020; 76(2): 309-16.
[http://dx.doi.org/10.3233/CH-209206] [PMID: 32925010]
[69]
Canyelles M, Tondo M, Cedó L, Farràs M, Escolà-Gil J, Blanco-Vaca F. Trimethylamine N-Oxide: A link among diet, gut microbiota, gene regulation of liver and intestine cholesterol homeostasis and hdl function. Int J Mol Sci 2018; 19(10): 3228.
[http://dx.doi.org/10.3390/ijms19103228] [PMID: 30347638]
[70]
Koeth RA, Wang Z, Levison BS, et al. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 2013; 19(5): 576-85.
[http://dx.doi.org/10.1038/nm.3145] [PMID: 23563705]
[71]
Ding L, Chang M, Guo Y, et al. Trimethylamine-N-oxide (TMAO)-induced atherosclerosis is associated with bile acid metabolism. Lipids Health Dis 2018; 17(1): 286.
[http://dx.doi.org/10.1186/s12944-018-0939-6] [PMID: 30567573]
[72]
Jomard A, Liberale L, Doytcheva P, et al. Effects of acute administration of trimethylamine N-oxide on endothelial function: a translational study. Sci Rep 2022; 12(1): 8664.
[http://dx.doi.org/10.1038/s41598-022-12720-5] [PMID: 35606406]
[73]
Warrier M, Shih DM, Burrows AC, et al. The TMAO-generating enzyme flavin monooxygenase 3 is a central regulator of cholesterol balance. Cell Rep 2015; 10(3): 326-38.
[http://dx.doi.org/10.1016/j.celrep.2014.12.036] [PMID: 25600868]
[74]
Liang X, Zhang Z, Lv Y, et al. Reduction of intestinal trimethylamine by probiotics ameliorated lipid metabolic disorders associated with atherosclerosis. Nutrition 2020; 79-80: 110941.
[http://dx.doi.org/10.1016/j.nut.2020.110941] [PMID: 32858376]
[75]
Geng J, Yang C, Wang B, et al. Trimethylamine N-oxide promotes atherosclerosis via CD36-dependent MAPK/JNK pathway. Biomed Pharmacother 2018; 97: 941-7.
[http://dx.doi.org/10.1016/j.biopha.2017.11.016] [PMID: 29136772]
[76]
Mohammadi A, Najar AG, Yaghoobi MM, Jahani Y, Vahabzadeh Z. Trimethylamine-N-oxide treatment induces changes in the atp-binding cassette transporter a1 and scavenger receptor a1 in murine macrophage J774A.1 cells. Inflammation 2016; 39(1): 393-404.
[http://dx.doi.org/10.1007/s10753-015-0261-7] [PMID: 26412259]
[77]
Wu P, Chen J, Chen J, et al. Trimethylamine N-oxide promotes apoE −/− mice atherosclerosis by inducing vascular endothelial cell pyroptosis via the SDHB/ROS pathway. J Cell Physiol 2020; 235(10): 6582-91.
[http://dx.doi.org/10.1002/jcp.29518] [PMID: 32012263]
[78]
Shih DM, Wang Z, Lee R, et al. Flavin containing monooxygenase 3 exerts broad effects on glucose and lipid metabolism and atherosclerosis. J Lipid Res 2015; 56(1): 22-37.
[http://dx.doi.org/10.1194/jlr.M051680] [PMID: 25378658]
[79]
Collins HL, Drazul-Schrader D, Sulpizio AC, et al. L-Carnitine intake and high trimethylamine N-oxide plasma levels correlate with low aortic lesions in ApoE−/− transgenic mice expressing CETP. Atherosclerosis 2016; 244: 29-37.
[http://dx.doi.org/10.1016/j.atherosclerosis.2015.10.108] [PMID: 26584136]
[80]
Trøseid M, Hov JR, Nestvold TK, et al. Major increase in microbiota-dependent proatherogenic metabolite TMAO one year after bariatric surgery. Metab Syndr Relat Disord 2016; 14(4): 197-201.
[http://dx.doi.org/10.1089/met.2015.0120] [PMID: 27081744]
[81]
Zhu W, Gregory JC, Org E, et al. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell 2016; 165(1): 111-24.
[http://dx.doi.org/10.1016/j.cell.2016.02.011] [PMID: 26972052]
[82]
Gong D, Zhang L, Zhang Y, Wang F, Zhao Z, Zhou X. Gut microbial metabolite trimethylamine n-oxide is related to thrombus formation in atrial fibrillation patients. Am J Med Sci 2019; 358(6): 422-8.
[http://dx.doi.org/10.1016/j.amjms.2019.09.002] [PMID: 31666184]
[83]
Tang WHW, Wang Z, Levison BS, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med 2013; 368(17): 1575-84.
[http://dx.doi.org/10.1056/NEJMoa1109400] [PMID: 23614584]
[84]
Zhu W, Wang Z, Tang WHW, Hazen SL. Gut microbe-generated trimethylamine n -oxide from dietary choline is prothrombotic in subjects. Circulation 2017; 135(17): 1671-3.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.116.025338] [PMID: 28438808]
[85]
Zhu W, Buffa JA, Wang Z, et al. Flavin monooxygenase 3, the host hepatic enzyme in the metaorganismal trimethylamine N-oxide-generating pathway, modulates platelet responsiveness and thrombosis risk. J Thromb Haemost 2018; 16(9): 1857-72.
[http://dx.doi.org/10.1111/jth.14234] [PMID: 29981269]
[86]
Bourguignon LYW, Jin H. Identification of the ankyrin-binding domain of the mouse T-lymphoma cell inositol 1,4,5-trisphosphate (IP3) receptor and its role in the regulation of IP3-mediated internal Ca2+ release. J Biol Chem 1995; 270(13): 7257-60.
[http://dx.doi.org/10.1074/jbc.270.13.7257] [PMID: 7706265]
[87]
Witkowski M, Witkowski M, Friebel J, et al. Vascular endothelial tissue factor contributes to trimethylamine N-oxide-enhanced arterial thrombosis. Cardiovasc Res 2022; 118(10): 2367-84.
[http://dx.doi.org/10.1093/cvr/cvab263] [PMID: 34352109]
[88]
Dumitrescu L, Popescu-Olaru I, Cozma L, et al. Oxidative Stress and the Microbiota-Gut-Brain Axis. Oxid Med Cell Longev 2018; 2018: 1-12.
[http://dx.doi.org/10.1155/2018/2406594] [PMID: 30622664]
[89]
Li C, Zhu L, Dai Y, et al. Diet-induced high serum levels of trimethylamine-N-oxide enhance the cellular inflammatory response without exacerbating acute intracerebral hemorrhage injury in mice. Oxid Med Cell Longev 2022; 2022: 1-16.
[http://dx.doi.org/10.1155/2022/1599747] [PMID: 35242275]
[90]
Spychala MS, Venna VR, Jandzinski M, et al. Age-related changes in the gut microbiota influence systemic inflammation and stroke outcome. Ann Neurol 2018; 84(1): 23-36.
[http://dx.doi.org/10.1002/ana.25250] [PMID: 29733457]
[91]
Chen H, Li J, Li N, Liu H, Tang J. Increased circulating trimethylamine N-oxide plays a contributory role in the development of endothelial dysfunction and hypertension in the RUPP rat model of preeclampsia. Hypertens Pregnancy 2019; 38(2): 96-104.
[http://dx.doi.org/10.1080/10641955.2019.1584630] [PMID: 30821524]
[92]
Seldin MM, Meng Y, Qi H, et al. Trimethylamine n-oxide promotes vascular inflammation through signaling of mitogen-activated protein kinase and nuclear Factor-κB. J Am Heart Assoc 2016; 5(2): e002767.
[http://dx.doi.org/10.1161/JAHA.115.002767] [PMID: 26903003]
[93]
Liu X, Shao Y, Tu J, et al. Trimethylamine-N-oxide-stimulated hepatocyte-derived exosomes promote inflammation and endothelial dysfunction through nuclear factor-kappa B signaling. Ann Transl Med 2021; 9(22): 1670.
[http://dx.doi.org/10.21037/atm-21-5043] [PMID: 34988179]
[94]
Pateras I, Giaginis C, Tsigris C, Patsouris E, Theocharis S NF. -κB signaling at the crossroads of inflammation and atherogenesis: searching for new therapeutic links. Expert Opin Ther Targets 2014; 18(9): 1089-101.
[http://dx.doi.org/10.1517/14728222.2014.938051] [PMID: 25005042]
[95]
Sun X, Jiao X, Ma Y, et al. Trimethylamine N-oxide induces inflammation and endothelial dysfunction in human umbilical vein endothelial cells via activating ROS-TXNIP-NLRP3 inflammasome. Biochem Biophys Res Commun 2016; 481(1-2): 63-70.
[http://dx.doi.org/10.1016/j.bbrc.2016.11.017] [PMID: 27833015]
[96]
Boini KM, Hussain T, Li PL, Koka SS. Trimethylamine-n-oxide instigates nlrp3 inflammasome activation and endothelial dysfunction. Cell Physiol Biochem 2017; 44(1): 152-62.
[http://dx.doi.org/10.1159/000484623] [PMID: 29130962]
[97]
Brunt VE, Gioscia-Ryan RA, Casso AG, et al. Trimethylamine-n-oxide promotes age-related vascular oxidative stress and endothelial dysfunction in mice and healthy humans. Hypertension 2020; 76(1): 101-12.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.14759] [PMID: 32520619]
[98]
Li T, Chen Y, Gua C, Li X. Elevated circulating trimethylamine n-oxide levels contribute to endothelial dysfunction in aged rats through vascular inflammation and oxidative stress. Front Physiol 2017; 8: 350.
[http://dx.doi.org/10.3389/fphys.2017.00350] [PMID: 28611682]
[99]
Singh GB, Zhang Y, Boini KM, Koka S. High mobility group box 1 mediates tmao-induced endothelial dysfunction. Int J Mol Sci 2019; 20(14): 3570.
[http://dx.doi.org/10.3390/ijms20143570] [PMID: 31336567]
[100]
Woltjer RL, McMahan W, Milatovic D, et al. Effects of chemical chaperones on oxidative stress and detergent-insoluble species formation following conditional expression of amyloid precursor protein carboxy-terminal fragment. Neurobiol Dis 2007; 25(2): 427-37.
[http://dx.doi.org/10.1016/j.nbd.2006.10.003] [PMID: 17141508]
[101]
Lupachyk S, Watcho P, Stavniichuk R, Shevalye H, Obrosova IG. Endoplasmic reticulum stress plays a key role in the pathogenesis of diabetic peripheral neuropathy. Diabetes 2013; 62(3): 944-52.
[http://dx.doi.org/10.2337/db12-0716] [PMID: 23364451]
[102]
Fukami K, Yamagishi S, Sakai K, et al. Oral L-carnitine supplementation increases trimethylamine-N-oxide but reduces markers of vascular injury in hemodialysis patients. J Cardiovasc Pharmacol 2015; 65(3): 289-95.
[http://dx.doi.org/10.1097/FJC.0000000000000197] [PMID: 25636076]
[103]
Dickstein DL, Kabaso D, Rocher AB, Luebke JI, Wearne SL, Hof PR. Changes in the structural complexity of the aged brain. Aging Cell 2007; 6(3): 275-84.
[http://dx.doi.org/10.1111/j.1474-9726.2007.00289.x] [PMID: 17465981]
[104]
Harada CN, Natelson Love MC, Triebel KL. Normal cognitive aging. Clin Geriatr Med 2013; 29(4): 737-52.
[http://dx.doi.org/10.1016/j.cger.2013.07.002] [PMID: 24094294]
[105]
Chen Y, Xu J, Chen Y. Regulation of neurotransmitters by the gut microbiota and effects on cognition in neurological disorders. Nutrients 2021; 13(6): 2099.
[http://dx.doi.org/10.3390/nu13062099] [PMID: 34205336]
[106]
Li S, Shao Y, Li K, et al. Vascular cognitive impairment and the gut microbiota. J Alzheimers Dis 2018; 63(4): 1209-22.
[http://dx.doi.org/10.3233/JAD-171103] [PMID: 29689727]
[107]
Ticinesi A, Tana C, Nouvenne A, Prati B, Lauretani F, Meschi T. Gut microbiota, cognitive frailty and dementia in older individuals: A systematic review. Clin Interv Aging 2018; 13: 1497-511.
[http://dx.doi.org/10.2147/CIA.S139163] [PMID: 30214170]
[108]
Luo Y, Zhao P, Dou M, et al. Exogenous microbiota-derived metabolite trimethylamine N-oxide treatment alters social behaviors: Involvement of hippocampal metabolic adaptation. Neuropharmacology 2021; 191: 108563.
[http://dx.doi.org/10.1016/j.neuropharm.2021.108563] [PMID: 33887311]
[109]
Mao J, Zhao P, Wang Q, et al. Repeated 3,3-Dimethyl-1-butanol exposure alters social dominance in adult mice. Neurosci Lett 2021; 758: 136006.
[http://dx.doi.org/10.1016/j.neulet.2021.136006] [PMID: 34098029]
[110]
Lanz M, Janeiro MH, Milagro FI, et al. Trimethylamine N-oxide (TMAO) drives insulin resistance and cognitive deficiencies in a senescence accelerated mouse model. Mech Ageing Dev 2022; 204: 111668.
[http://dx.doi.org/10.1016/j.mad.2022.111668] [PMID: 35341897]
[111]
Sanguinetti E, Collado MC, Marrachelli VG, et al. Microbiome-metabolome signatures in mice genetically prone to develop dementia, fed a normal or fatty diet. Sci Rep 2018; 8(1): 4907.
[http://dx.doi.org/10.1038/s41598-018-23261-1] [PMID: 29559675]
[112]
Li D, Ke Y, Zhan R, et al. Trimethylamine- N -oxide promotes brain aging and cognitive impairment in mice. Aging Cell 2018; 17(4): e12768.
[http://dx.doi.org/10.1111/acel.12768] [PMID: 29749694]
[113]
Mueed Z, Mehta D, Rai PK, Kamal MA, Poddar NK. Cross-Interplay between Osmolytes and mTOR in Alzheimer’s disease pathogenesis. Curr Pharm Des 2020; 26(37): 4699-711.
[http://dx.doi.org/10.2174/1381612826666200518112355] [PMID: 32418522]
[114]
Meng F, Li N, Li D, Song B, Li L. The presence of elevated circulating trimethylamine N-oxide exaggerates postoperative cognitive dysfunction in aged rats. Behav Brain Res 2019; 368: 111902.
[http://dx.doi.org/10.1016/j.bbr.2019.111902] [PMID: 30980850]
[115]
Zhao L, Zhang C, Cao G, Dong X, Li D, Jiang L. Higher circulating trimethylamine N-oxide sensitizes sevoflurane-induced cognitive dysfunction in aged rats probably by downregulating hippocampal methionine sulfoxide reductase A. Neurochem Res 2019; 44(11): 2506-16.
[http://dx.doi.org/10.1007/s11064-019-02868-4] [PMID: 31486012]
[116]
Du D, Tang W, Zhou C, et al. Fecal microbiota transplantation is a promising method to restore gut microbiota dysbiosis and relieve neurological deficits after traumatic brain injury. Oxid Med Cell Longev 2021; 2021: 1-21.
[http://dx.doi.org/10.1155/2021/5816837] [PMID: 33628361]
[117]
Rabinovici GD. Late-onset Alzheimer Disease. Continuum (Minneap Minn) 2019; 25(1): 14-33.
[http://dx.doi.org/10.1212/CON.0000000000000700] [PMID: 30707185]
[118]
Calderon-Garcidueñas AL, Duyckaerts C. Alzheimer disease. Handb Clin Neurol 2018; 145: 325-37.
[http://dx.doi.org/10.1016/B978-0-12-802395-2.00023-7] [PMID: 28987180]
[119]
Haran JP, Bhattarai SK, Foley SE, et al. Alzheimer’s disease microbiome is associated with dysregulation of the anti-inflammatory p-glycoprotein pathway. MBio 2019; 10(3): e00632-19.
[http://dx.doi.org/10.1128/mBio.00632-19] [PMID: 31064831]
[120]
Verhaar BJH, Hendriksen HMA, de Leeuw FA, et al. Gut microbiota composition is related to ad pathology. Front Immunol 2022; 12: 794519.
[http://dx.doi.org/10.3389/fimmu.2021.794519] [PMID: 35173707]
[121]
Buawangpong N, Pinyopornpanish K, Siri-Angkul N, Chattipakorn N, Chattipakorn SC. The role of trimethylamine-N-Oxide in the development of Alzheimer’s disease. J Cell Physiol 2022; 237(3): 1661-85.
[http://dx.doi.org/10.1002/jcp.30646] [PMID: 34812510]
[122]
Vogt NM, Romano KA, Darst BF, et al. The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer’s disease. Alzheimers Res Ther 2018; 10(1): 124.
[http://dx.doi.org/10.1186/s13195-018-0451-2] [PMID: 30579367]
[123]
Yilmaz A, Ugur Z, Bisgin H, et al. Targeted metabolic profiling of urine highlights a potential biomarker panel for the diagnosis of alzheimer’s disease and mild cognitive impairment: A pilot study. Metabolites 2020; 10(9): 357.
[http://dx.doi.org/10.3390/metabo10090357] [PMID: 32878308]
[124]
Zhuang Z, Gao M, Yang R, Liu Z, Cao W, Huang T. Causal relationships between gut metabolites and Alzheimer’s disease: a bidirectional Mendelian randomization study. Neurobiol Aging 2021; 100(119): 115-9.
[http://dx.doi.org/10.1016/j.neurobiolaging.2020.10.022]
[125]
Yang DS, Yip CM, Huang THJ, Chakrabartty A, Fraser PE. Manipulating the amyloid-β aggregation pathway with chemical chaperones. J Biol Chem 1999; 274(46): 32970-4.
[http://dx.doi.org/10.1074/jbc.274.46.32970] [PMID: 10551864]
[126]
Kumari A, Rajput R, Shrivastava N, Somvanshi P, Grover A. Synergistic approaches unraveling regulation and aggregation of intrinsically disordered β-amyloids implicated in Alzheimer’s disease. Int J Biochem Cell Biol 2018; 99: 19-27.
[http://dx.doi.org/10.1016/j.biocel.2018.03.014] [PMID: 29571707]
[127]
Cho SS, Reddy G, Straub JE, Thirumalai D. Entropic stabilization of proteins by TMAO. J Phys Chem B 2011; 115(45): 13401-7.
[http://dx.doi.org/10.1021/jp207289b] [PMID: 21985427]
[128]
Liao YT, Manson AC, DeLyser MR, Noid WG, Cremer PS. Trimethylamine N -oxide stabilizes proteins via a distinct mechanism compared with betaine and glycine. Proc Natl Acad Sci 2017; 114(10): 2479-84.
[http://dx.doi.org/10.1073/pnas.1614609114] [PMID: 28228526]
[129]
Levine ZA, Larini L, LaPointe NE, Feinstein SC, Shea JE. Regulation and aggregation of intrinsically disordered peptides. Proc Natl Acad Sci USA 2015; 112(9): 2758-63.
[http://dx.doi.org/10.1073/pnas.1418155112] [PMID: 25691742]
[130]
Scaramozzino F, Peterson DW, Farmer P, Gerig JT, Graves DJ, Lew J. TMAO promotes fibrillization and microtubule assembly activity in the C-terminal repeat region of tau. Biochemistry 2006; 45(11): 3684-91.
[http://dx.doi.org/10.1021/bi052167g] [PMID: 16533051]
[131]
Esler WP, Wolfe MS. A portrait of Alzheimer secretases--new features and familiar faces. Science 2001; 293(5534): 1449-54.
[http://dx.doi.org/10.1126/science.1064638] [PMID: 11520976]
[132]
Gao Q, Wang Y, Wang X, et al. Decreased levels of circulating trimethylamine N-oxide alleviate cognitive and pathological deterioration in transgenic mice: a potential therapeutic approach for Alzheimer’s disease. Aging 2019; 11(19): 8642-63.
[http://dx.doi.org/10.18632/aging.102352] [PMID: 31612864]
[133]
Govindarajulu M, Pinky PD, Steinke I, et al. Gut metabolite TMAO induces synaptic plasticity deficits by promoting endoplasmic reticulum stress. Front Mol Neurosci 2020; 13: 138.
[http://dx.doi.org/10.3389/fnmol.2020.00138] [PMID: 32903435]
[134]
Wang Q-J, Shen Y-E, Wang X, et al. Concomitant memantine and treatment attenuates cognitive impairments in APP/PS1 mice. Aging 2020; 12(1): 628-49.
[http://dx.doi.org/10.18632/aging.102645] [PMID: 31907339]
[135]
Veitinger M, Oehler R, Umlauf E, et al. A platelet protein biochip rapidly detects an Alzheimer’s disease-specific phenotype. Acta Neuropathol 2014; 128(5): 665-77.
[http://dx.doi.org/10.1007/s00401-014-1341-8] [PMID: 25248508]
[136]
Colciaghi F, Marcello E, Borroni B, et al. Platelet APP, ADAM 10 and BACE alterations in the early stages of Alzheimer disease. Neurology 2004; 62(3): 498-501.
[http://dx.doi.org/10.1212/01.WNL.0000106953.49802.9C] [PMID: 14872043]
[137]
Canobbio I, Visconte C, Momi S, et al. Platelet amyloid precursor protein is a modulator of venous thromboembolism in mice. Blood 2017; 130(4): 527-36.
[http://dx.doi.org/10.1182/blood-2017-01-764910] [PMID: 28611024]
[138]
Jarre A, Gowert NS, Donner L, et al. Pre-activated blood platelets and a pro-thrombotic phenotype in APP23 mice modeling Alzheimer’s disease. Cell Signal 2014; 26(9): 2040-50.
[http://dx.doi.org/10.1016/j.cellsig.2014.05.019] [PMID: 24928203]
[139]
Armstrong MJ, Okun MS. Diagnosis and treatment of parkinson disease. JAMA 2020; 323(6): 548-60.
[http://dx.doi.org/10.1001/jama.2019.22360] [PMID: 32044947]
[140]
Alpha-synuclein in Lewy bodies. Nature 1997; 388(6645): 839-40.
[http://dx.doi.org/10.1038/42166]
[141]
Bencs V, Bencze J, Módis VL, Simon V, Kálmán J, Hortobágyi T. Pathological and clinical comparison of Parkinson’s disease dementia and dementia with Lewy bodies Orv Hetil 2020; 161(18): 727-37.
[http://dx.doi.org/10.1556/650.2020.31715] [PMID: 32338488]
[142]
Bendor JT, Logan TP, Edwards RH. The Function of α-. Synuclein Neuron 2013; 79(6): 1044-66.
[http://dx.doi.org/10.1016/j.neuron.2013.09.004] [PMID: 24050397]
[143]
Caputi V, Giron M. Microbiome-gut-brain axis and toll-like receptors in parkinson’s disease. Int J Mol Sci 2018; 19(6): 1689.
[http://dx.doi.org/10.3390/ijms19061689] [PMID: 29882798]
[144]
Sampson TR, Debelius JW, Thron T, et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of parkinson’s disease. Cell 2016; 167(6): 1469-1480.e12.
[http://dx.doi.org/10.1016/j.cell.2016.11.018] [PMID: 27912057]
[145]
Sankowski B. Księżarczyk K, Raćkowska E, Szlufik S, Koziorowski D, Giebułtowicz J. Higher cerebrospinal fluid to plasma ratio of p-cresol sulfate and indoxyl sulfate in patients with Parkinson’s disease. Clin Chim Acta 2020; 501: 165-73.
[http://dx.doi.org/10.1016/j.cca.2019.10.038] [PMID: 31726035]
[146]
Kumari S, Goyal V, Kumaran SS, Dwivedi SN, Srivastava A, Jagannathan NR. Quantitative metabolomics of saliva using proton NMR spectroscopy in patients with Parkinson’s disease and healthy controls. Neurol Sci 2020; 41(5): 1201-10.
[http://dx.doi.org/10.1007/s10072-019-04143-4] [PMID: 31897951]
[147]
Chen SJ, Kuo CH, Kuo HC, et al. The gut metabolite trimethylamine n-oxide is associated with parkinson’s disease severity and progression. Mov Disord 2020; 35(11): 2115-6.
[http://dx.doi.org/10.1002/mds.28246] [PMID: 32875634]
[148]
Chung SJ, Rim JH, Ji D, et al. Gut microbiota-derived metabolite trimethylamine N-oxide as a biomarker in early Parkinson’s disease. Nutrition 2021; 83: 111090.
[http://dx.doi.org/10.1016/j.nut.2020.111090] [PMID: 33418492]
[149]
Tan AH, Chong CW, Lim SY, et al. Gut microbial ecosystem in parkinson disease: new clinicobiological insights from multi-omics. Ann Neurol 2021; 89(3): 546-59.
[http://dx.doi.org/10.1002/ana.25982] [PMID: 33274480]
[150]
Jahan I, Nayeem SM. Effect of osmolytes on conformational behavior of intrinsically disordered protein α-synuclein. Biophys J 2019; 117(10): 1922-34.
[http://dx.doi.org/10.1016/j.bpj.2019.09.046] [PMID: 31699336]
[151]
van der Flier WM, Skoog I, Schneider JA, et al. Vascular cognitive impairment. Nat Rev Dis Primers 2018; 4(1): 18003.
[http://dx.doi.org/10.1038/nrdp.2018.3] [PMID: 29446769]
[152]
Gorelick PB, Scuteri A, Black SE, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association. Stroke 2011; 42(9): 2672-713.
[http://dx.doi.org/10.1161/STR.0b013e3182299496] [PMID: 21778438]
[153]
Skrobot OA, Black SE, Chen C, et al. Progress toward standardized diagnosis of vascular cognitive impairment: Guidelines from the vascular impairment of cognition classification consensus study. Alzheimers Dement 2018; 14(3): 280-92.
[http://dx.doi.org/10.1016/j.jalz.2017.09.007] [PMID: 29055812]
[154]
Iadecola C, Duering M, Hachinski V, et al. Vascular cognitive impairment and dementia. J Am Coll Cardiol 2019; 73(25): 3326-44.
[http://dx.doi.org/10.1016/j.jacc.2019.04.034] [PMID: 31248555]
[155]
Mijajlović MD, Pavlović A, Brainin M, et al. Post-stroke dementia – a comprehensive review. BMC Med 2017; 15(1): 11.
[http://dx.doi.org/10.1186/s12916-017-0779-7] [PMID: 28095900]
[156]
Chinese stroke society, expert committee on management of post-stroke cognitive impairment: Expert consensus on management of post-stroke cognitive impairment. Chinese Stroke Journal 2017; 12(6): 519-31.
[http://dx.doi.org/10.3969/j.issn.1673-5765.2017.06.011]
[157]
Looi JCL, Sachdev PS. Differentiation of vascular dementia from AD on neuropsychological tests. Neurology 1999; 53(4): 670-8.
[http://dx.doi.org/10.1212/WNL.53.4.670] [PMID: 10489025]
[158]
Honig LS, Kukull W, Mayeux R. Atherosclerosis and AD: Analysis of data from the US National Alzheimer’s Coordinating Center. Neurology 2005; 64(3): 494-500.
[http://dx.doi.org/10.1212/01.WNL.0000150886.50187.30] [PMID: 15699381]
[159]
Jahrling JB, Lin AL, DeRosa N, et al. mTOR drives cerebral blood flow and memory deficits in LDLR −/− mice modeling atherosclerosis and vascular cognitive impairment. J Cereb Blood Flow Metab 2018; 38(1): 58-74.
[http://dx.doi.org/10.1177/0271678X17705973] [PMID: 28511572]
[160]
Gao X, Liu X, Xu J, Xue C, Xue Y, Wang Y. Dietary trimethylamine N-oxide exacerbates impaired glucose tolerance in mice fed a high fat diet. J Biosci Bioeng 2014; 118(4): 476-81.
[http://dx.doi.org/10.1016/j.jbiosc.2014.03.001] [PMID: 24721123]
[161]
Miralbell J, López-Cancio E, López-Oloriz J, et al. Cognitive patterns in relation to biomarkers of cerebrovascular disease and vascular risk factors. Cerebrovasc Dis 2013; 36(2): 98-105.
[http://dx.doi.org/10.1159/000352059] [PMID: 24029412]
[162]
Mirzaei R, Bouzari B, Hosseini-Fard SR, et al. Role of microbiota-derived short-chain fatty acids in nervous system disorders. Biomed Pharmacother 2021; 139: 111661.
[http://dx.doi.org/10.1016/j.biopha.2021.111661] [PMID: 34243604]
[163]
Wardlaw JM, Smith C, Dichgans M. Small vessel disease: mechanisms and clinical implications. Lancet Neurol 2019; 18(7): 684-96.
[http://dx.doi.org/10.1016/S1474-4422(19)30079-1] [PMID: 31097385]
[164]
Wardlaw JM, Smith EE, Biessels GJ, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 2013; 12(8): 822-38.
[http://dx.doi.org/10.1016/S1474-4422(13)70124-8] [PMID: 23867200]
[165]
Smith EE, Saposnik G, Biessels GJ, et al. Prevention of Stroke in Patients With Silent Cerebrovascular Disease: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2017; 48(2): e44-71.
[http://dx.doi.org/10.1161/STR.0000000000000116] [PMID: 27980126]
[166]
Li T, Huang Y, Cai W, et al. Age-related cerebral small vessel disease and inflammaging. Cell Death Dis 2020; 11(10): 932.
[http://dx.doi.org/10.1038/s41419-020-03137-x] [PMID: 33127878]
[167]
Tonomura S, Gyanwali B. Cerebral microbleeds in vascular dementia from clinical aspects to host-microbial interaction. Neurochem Int 2021; 148: 105073.
[http://dx.doi.org/10.1016/j.neuint.2021.105073] [PMID: 34048844]
[168]
Matsuura J, Inoue R, Takagi T, et al. Analysis of gut microbiota in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). J Clin Biochem Nutr 2019; 65(3): 240-4.
[http://dx.doi.org/10.3164/jcbn.19-22] [PMID: 31777426]
[169]
Saji N, Murotani K, Hisada T, et al. The Association between Cerebral Small Vessel Disease and the Gut Microbiome: A Cross-Sectional Analysis. J Stroke Cerebrovasc Dis 2021; 30(3): 105568.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105568] [PMID: 33423868]
[170]
Saji N, Saito Y, Yamashita T, et al. Relationship Between Plasma Lipopolysaccharides, Gut Microbiota, and Dementia: A Cross-Sectional Study. J Alzheimers Dis 2022; 86(4): 1947-57.
[http://dx.doi.org/10.3233/JAD-215653] [PMID: 35213381]
[171]
Cai W, Chen X, Men X, et al. Gut microbiota from patients with arteriosclerotic CSVD induces higher IL-17A production in neutrophils via activating RORγt. Sci Adv 2021; 7(4): eabe4827.
[http://dx.doi.org/10.1126/sciadv.abe4827] [PMID: 33523954]
[172]
Chen Y, Xu J, Pan Y, et al. Association of Trimethylamine N-Oxide and Its Precursor With Cerebral Small Vessel Imaging Markers. Front Neurol 2021; 12: 648702.
[http://dx.doi.org/10.3389/fneur.2021.648702] [PMID: 33868152]
[173]
Ji X, Tian L, Niu S, Yao S, Qu C. Trimethylamine N-oxide promotes demyelination in spontaneous hypertension rats through enhancing pyroptosis of oligodendrocytes. Front Aging Neurosci 2022; 14: 963876.
[http://dx.doi.org/10.3389/fnagi.2022.963876] [PMID: 36072486]
[174]
Nelson JW, Phillips SC, Ganesh BP, Petrosino JF, Durgan DJ, Bryan RM. The gut microbiome contributes to blood-brain barrier disruption in spontaneously hypertensive stroke prone rats. FASEB J 2021; 35(2): e21201.
[http://dx.doi.org/10.1096/fj.202001117R] [PMID: 33496989]
[175]
Pendlebury ST, Rothwell PM. Incidence and prevalence of dementia associated with transient ischaemic attack and stroke: analysis of the population-based Oxford Vascular Study. Lancet Neurol 2019; 18(3): 248-58.
[http://dx.doi.org/10.1016/S1474-4422(18)30442-3] [PMID: 30784556]
[176]
Qu Y, Zhuo L, Li N, et al. Prevalence of post-stroke cognitive impairment in china: a community-based, cross-sectional study. PLoS One 2015; 10(4): e0122864.
[http://dx.doi.org/10.1371/journal.pone.0122864] [PMID: 25874998]
[177]
Makin SDJ, Turpin S, Dennis MS, Wardlaw JM. Cognitive impairment after lacunar stroke: systematic review and meta-analysis of incidence, prevalence and comparison with other stroke subtypes. J Neurol Neurosurg Psychiatry 2013; 84(8): 893-900.
[http://dx.doi.org/10.1136/jnnp-2012-303645] [PMID: 23457225]
[178]
Gong L, Wang H, Zhu X, et al. Nomogram to predict cognitive dysfunction after a minor ischemic stroke in hospitalized-population. Front Aging Neurosci 2021; 13: 637363.
[http://dx.doi.org/10.3389/fnagi.2021.637363] [PMID: 33967738]
[179]
Lo JW, Crawford JD, Desmond DW, et al. Profile of and risk factors for poststroke cognitive impairment in diverse ethnoregional groups. Neurology 2019; 93(24): e2257-71.
[http://dx.doi.org/10.1212/WNL.0000000000008612] [PMID: 31712368]
[180]
Vascular Cognitive Impairment Branch of Chinese Stroke Society. Wang Kai, Dong Qiang, Yu Jintai, Hu Panpan: Expert Consensus on Management of Post-Stroke Cognitive Impairment 2021. Chinese Journal of Stroke 2021; 16(4): 14.
[181]
Rohde D, Gaynor E, Large M, et al. The Impact of Cognitive Impairment on poststroke outcomes: a 5-year follow-up. J Geriatr Psychiatry Neurol 2019; 32(5): 275-81.
[http://dx.doi.org/10.1177/0891988719853044] [PMID: 31167593]
[182]
Crichton SL, Bray BD, McKevitt C, Rudd AG, Wolfe CDA. Patient outcomes up to 15 years after stroke: survival, disability, quality of life, cognition and mental health. J Neurol Neurosurg Psychiatry 2016; 87(10): 1091-8.
[http://dx.doi.org/10.1136/jnnp-2016-313361] [PMID: 27451353]
[183]
Sun JH, Tan L, Yu JT. Post-stroke cognitive impairment: epidemiology, mechanisms and management. Ann Transl Med 2014; 2(8): 80.
[http://dx.doi.org/10.3978/j.issn.2305-5839.2014.08.05] [PMID: 25333055]
[184]
Mok VCT, Lam BYK, Wong A, Ko H, Markus HS, Wong LKS. Early-onset and delayed-onset poststroke dementia — revisiting the mechanisms. Nat Rev Neurol 2017; 13(3): 148-59.
[http://dx.doi.org/10.1038/nrneurol.2017.16] [PMID: 28211452]
[185]
Casolla B, Caparros F, Cordonnier C, et al. Biological and imaging predictors of cognitive impairment after stroke: A systematic review. J Neurol 2019; 266(11): 2593-604.
[http://dx.doi.org/10.1007/s00415-018-9089-z] [PMID: 30350168]
[186]
Zhang X, Bi X. Post-stroke cognitive impairment: A review focusing on molecular biomarkers. J Mol Neurosci 2020; 70(8): 1244-54.
[http://dx.doi.org/10.1007/s12031-020-01533-8] [PMID: 32219663]
[187]
Blum S, Luchsinger JA, Manly JJ, et al. Memory after silent stroke: Hippocampus and infarcts both matter. Neurology 2012; 78(1): 38-46.
[http://dx.doi.org/10.1212/WNL.0b013e31823ed0cc] [PMID: 22201111]
[188]
Li W, Huang R, Shetty RA, et al. Transient focal cerebral ischemia induces long-term cognitive function deficit in an experimental ischemic stroke model. Neurobiol Dis 2013; 59: 18-25.
[http://dx.doi.org/10.1016/j.nbd.2013.06.014] [PMID: 23845275]
[189]
Cuartero MI, de la Parra J, Pérez-Ruiz A, et al. Abolition of aberrant neurogenesis ameliorates cognitive impairment after stroke in mice. J Clin Invest 2019; 129(4): 1536-50.
[http://dx.doi.org/10.1172/JCI120412] [PMID: 30676325]
[190]
Alawieh AM, Langley EF, Feng W, Spiotta AM, Tomlinson S. Complement-dependent synaptic uptake and cognitive decline after stroke and reperfusion therapy. J Neurosci 2020; 40(20): 4042-58.
[http://dx.doi.org/10.1523/JNEUROSCI.2462-19.2020] [PMID: 32291326]
[191]
Sun H, He X, Tao X, et al. The CD200/CD200R signaling pathway contributes to spontaneous functional recovery by enhancing synaptic plasticity after stroke. J Neuroinflammation 2020; 17(1): 171.
[http://dx.doi.org/10.1186/s12974-020-01845-x] [PMID: 32473633]
[192]
Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 2010; 9(7): 689-701.
[http://dx.doi.org/10.1016/S1474-4422(10)70104-6] [PMID: 20610345]
[193]
Kooistra M, Geerlings MI, van der Graaf Y, et al. Vascular brain lesions, brain atrophy, and cognitive decline. The Second Manifestations of ARTerial disease—Magnetic Resonance (SMART-MR) study. Neurobiol Aging 2014; 35(1): 35-41.
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.07.004] [PMID: 23932882]
[194]
Poels MMF, Ikram MA, van der Lugt A, et al. Cerebral microbleeds are associated with worse cognitive function: The Rotterdam Scan Study. Neurology 2012; 78(5): 326-33.
[http://dx.doi.org/10.1212/WNL.0b013e3182452928] [PMID: 22262748]
[195]
Genin E, Hannequin D, Wallon D, et al. APOE and Alzheimer disease: a major gene with semi-dominant inheritance. Mol Psychiatry 2011; 16(9): 903-7.
[http://dx.doi.org/10.1038/mp.2011.52] [PMID: 21556001]
[196]
Bell RD, Winkler EA, Singh I, et al. Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature 2012; 485(7399): 512-6.
[http://dx.doi.org/10.1038/nature11087] [PMID: 22622580]
[197]
Montagne A, Nation DA, Sagare AP, et al. APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline. Nature 2020; 581(7806): 71-6.
[http://dx.doi.org/10.1038/s41586-020-2247-3] [PMID: 32376954]
[198]
Pendlebury ST, Poole D, Burgess A, Duerden J, Rothwell PM, Oxford Vascular S. APOE-ε4 genotype and dementia before and after transient ischemic attack and stroke. Stroke 2020; 51(3): 751-8.
[http://dx.doi.org/10.1161/STROKEAHA.119.026927] [PMID: 32070224]
[199]
Liu Y, Kong C, Gong L, et al. The association of post-stroke cognitive impairment and gut microbiota and its corresponding metabolites. J Alzheimers Dis 2020; 73(4): 1455-66.
[http://dx.doi.org/10.3233/JAD-191066] [PMID: 31929168]
[200]
Huang Y, Shen Z, He W. Identification of gut microbiome signatures in patients with post-stroke cognitive impairment and affective disorder. Front Aging Neurosci 2021; 13: 706765.
[http://dx.doi.org/10.3389/fnagi.2021.706765] [PMID: 34489677]
[201]
Ling Y, Gong T, Zhang J, et al. Gut microbiome signatures are biomarkers for cognitive impairment in patients with ischemic stroke. Front Aging Neurosci 2020; 12: 511562.
[http://dx.doi.org/10.3389/fnagi.2020.511562] [PMID: 33192448]
[202]
Ling Y, Gu Q, Zhang J, et al. Structural change of gut microbiota in patients with post-stroke comorbid cognitive impairment and depression and its correlation with clinical features. J Alzheimers Dis 2020; 77(4): 1595-608.
[http://dx.doi.org/10.3233/JAD-200315] [PMID: 32925035]
[203]
To M, Sugimoto M, Saruta J, et al. Cognitive dysfunction in a mouse model of cerebral ischemia influences salivary metabolomics. J Clin Med 2021; 10(8): 1698.
[http://dx.doi.org/10.3390/jcm10081698] [PMID: 33920851]
[204]
Zhu C, Li G, Lv Z, et al. Association of plasma trimethylamine-N-oxide levels with post-stroke cognitive impairment: a 1-year longitudinal study. Neurol Sci 2020; 41(1): 57-63.
[http://dx.doi.org/10.1007/s10072-019-04040-w] [PMID: 31420758]
[205]
Zhong C, Lu Z, Che B, et al. Choline pathway nutrients and metabolites and cognitive impairment after acute ischemic stroke. Stroke 2021; 52(3): 887-95.
[http://dx.doi.org/10.1161/STROKEAHA.120.031903] [PMID: 33467878]
[206]
Erny D. Hrabě de Angelis AL, Jaitin D, et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci 2015; 18(7): 965-77.
[http://dx.doi.org/10.1038/nn.4030] [PMID: 26030851]
[207]
Zhong C, Miao M, Che B, et al. Plasma choline and betaine and risks of cardiovascular events and recurrent stroke after ischemic stroke. Am J Clin Nutr 2021; 114(4): 1351-9.
[http://dx.doi.org/10.1093/ajcn/nqab199] [PMID: 34159355]
[208]
Ylilauri MPT, Voutilainen S, Lönnroos E, et al. Associations of dietary choline intake with risk of incident dementia and with cognitive performance: the Kuopio Ischaemic Heart Disease Risk Factor Study. Am J Clin Nutr 2019; 110(6): 1416-23.
[http://dx.doi.org/10.1093/ajcn/nqz148] [PMID: 31360988]
[209]
Poly C, Massaro JM, Seshadri S, et al. The relation of dietary choline to cognitive performance and white-matter hyperintensity in the Framingham Offspring Cohort. Am J Clin Nutr 2011; 94(6): 1584-91.
[http://dx.doi.org/10.3945/ajcn.110.008938] [PMID: 22071706]
[210]
Wallace TC. A comprehensive review of eggs, choline, and lutein on cognition across the life-span. J Am Coll Nutr 2018; 37(4): 269-85.
[http://dx.doi.org/10.1080/07315724.2017.1423248] [PMID: 29451849]
[211]
Blusztajn J, Slack B, Mellott T. Neuroprotective actions of dietary choline. Nutrients 2017; 9(8): 815.
[http://dx.doi.org/10.3390/nu9080815] [PMID: 28788094]
[212]
Zeisel SH. Dietary choline deficiency causes DNA strand breaks and alters epigenetic marks on DNA and histones. Mutat Res 2012; 733(1-2): 34-8.
[http://dx.doi.org/10.1016/j.mrfmmm.2011.10.008] [PMID: 22041500]
[213]
Velazquez R, Ferreira E, Knowles S, et al. Lifelong choline supplementation ameliorates Alzheimer’s disease pathology and associated cognitive deficits by attenuating microglia activation. Aging Cell 2019; 18(6): e13037.
[http://dx.doi.org/10.1111/acel.13037] [PMID: 31560162]
[214]
Eicher TP, Mohajeri MH. Overlapping mechanisms of action of brain-active bacteria and bacterial metabolites in the pathogenesis of common brain diseases. Nutrients 2022; 14(13): 2661.
[http://dx.doi.org/10.3390/nu14132661] [PMID: 35807841]
[215]
Casso AG, VanDongen NS, Gioscia-Ryan RA, et al. Initiation of 3,3-dimethyl-1-butanol at midlife prevents endothelial dysfunction and attenuates in vivo aortic stiffening with ageing in mice. J Physiol 2022; 600(21): 4633-51.
[http://dx.doi.org/10.1113/JP283581] [PMID: 36111692]
[216]
Chai GS, Jiang X, Ni ZF, et al. Betaine attenuates Alzheimer-like pathological changes and memory deficits induced by homocysteine. J Neurochem 2013; 124(3): 388-96.
[http://dx.doi.org/10.1111/jnc.12094] [PMID: 23157378]
[217]
Qi W, Zhang A, Good TA, Fernandez EJ. Two disaccharides and trimethylamine N-oxide affect Abeta aggregation differently, but all attenuate oligomer-induced membrane permeability. Biochemistry 2009; 48(37): 8908-19.
[http://dx.doi.org/10.1021/bi9006397] [PMID: 19637920]
[218]
Getter T, Zaks I, Barhum Y, et al. A chemical chaperone-based drug candidate is effective in a mouse model of amyotrophic lateral sclerosis (ALS). ChemMedChem 2015; 10(5): 850-61.
[http://dx.doi.org/10.1002/cmdc.201500045] [PMID: 25772747]
[219]
Yoshida H, Yoshizawa T, Shibasaki F, Shoji S, Kanazawa I. Chemical chaperones reduce aggregate formation and cell death caused by the truncated Machado-Joseph disease gene product with an expanded polyglutamine stretch. Neurobiol Dis 2002; 10(2): 88-99.
[http://dx.doi.org/10.1006/nbdi.2002.0502] [PMID: 12127147]
[220]
Aliev G, Ashraf GM, Kaminsky YG, et al. Implication of the nutritional and nonnutritional factors in the context of preservation of cognitive performance in patients with dementia/depression and Alzheimer disease. Am J Alzheimers Dis Other Demen 2013; 28(7): 660-70.
[http://dx.doi.org/10.1177/1533317513504614] [PMID: 24085255]
[221]
Bragin V, Chemodanova M, Dzhafarova N, Bragin I, Czerniawski JL, Aliev G. Integrated treatment approach improves cognitive function in demented and clinically depressed patients. Am J Alzheimers Dis Other Demen 2005; 20(1): 21-6.
[http://dx.doi.org/10.1177/153331750502000103] [PMID: 15751450]
[222]
Farokhi-Sisakht F, Farhoudi M, Sadigh-Eteghad S, Mahmoudi J, Mohaddes G. Cognitive rehabilitation improves ischemic stroke-induced cognitive impairment: role of growth factors. J Stroke Cerebrovasc Dis 2019; 28(10): 104299.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2019.07.015] [PMID: 31371141]
[223]
Wang C, Zhang Q, Yu K, Shen X, Wu Y, Wu J. Enriched environment promoted cognitive function via bilateral synaptic remodeling after cerebral ischemia. Front Neurol 2019; 10: 1189.
[http://dx.doi.org/10.3389/fneur.2019.01189] [PMID: 31781025]
[224]
Cavalcanti Neto MP, Aquino JS, Romão da Silva LF, et al. Gut microbiota and probiotics intervention: A potential therapeutic target for management of cardiometabolic disorders and chronic kidney disease? Pharmacol Res 2018; 130: 152-63.
[http://dx.doi.org/10.1016/j.phrs.2018.01.020] [PMID: 29410236]
[225]
Tuohy KM, Fava F, Viola R. ‘The way to a man’s heart is through his gut microbiota’ – dietary pro- and prebiotics for the management of cardiovascular risk. Proc Nutr Soc 2014; 73(2): 172-85.
[http://dx.doi.org/10.1017/S0029665113003911] [PMID: 24495527]
[226]
Bentham Science Publisher BSP. Lovegrove JA, Gitau R, Jackson KG, Tuohy KM. The gut microbiota and lipid metabolism: implications for human health and coronary heart disease. Curr Med Chem 2006; 13(25): 3005-21.
[http://dx.doi.org/10.2174/092986706778521814] [PMID: 17073643]
[227]
Román GC, Jackson RE, Gadhia R, Román AN, Reis J. Mediterranean diet: The role of long-chain ω-3 fatty acids in fish; polyphenols in fruits, vegetables, cereals, coffee, tea, cacao and wine; probiotics and vitamins in prevention of stroke, age-related cognitive decline, and Alzheimer disease. Rev Neurol 2019; 175(10): 724-41.
[http://dx.doi.org/10.1016/j.neurol.2019.08.005] [PMID: 31521398]
[228]
Vasquez EC, Aires R, Ton AMM, Amorim FG. New insights on the beneficial effects of the probiotic kefir on vascular dysfunction in cardiovascular and neurodegenerative diseases. Curr Pharm Des 2020; 26(30): 3700-10.
[http://dx.doi.org/10.2174/1381612826666200304145224] [PMID: 32129163]
[229]
Yang X, Yu D, Xue L, Li H, Du J. Probiotics modulate the microbiota-gut-brain axis and improve memory deficits in aged SAMP8 mice. Acta Pharm Sin B 2020; 10(3): 475-87.
[http://dx.doi.org/10.1016/j.apsb.2019.07.001] [PMID: 32140393]
[230]
Chen M, Yi L, Zhang Y, et al. Resveratrol attenuates trimethylamine- N -Oxide (TMAO)-induced atherosclerosis by regulating TMAO synthesis and bile acid metabolism via remodeling of the gut microbiota. MBio 2016; 7(2): e02210-5.
[http://dx.doi.org/10.1128/mBio.02210-15] [PMID: 27048804]
[231]
Bravo JA, Forsythe P, Chew MV, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci 2011; 108(38): 16050-5.
[http://dx.doi.org/10.1073/pnas.1102999108] [PMID: 21876150]
[232]
Ait-Belgnaoui A, Colom A, Braniste V, et al. Probiotic gut effect prevents the chronic psychological stress-induced brain activity abnormality in mice. Neurogastroenterol Motil 2014; 26(4): 510-20.
[http://dx.doi.org/10.1111/nmo.12295] [PMID: 24372793]
[233]
Haak BW, Westendorp WF, van Engelen TSR, et al. Disruptions of anaerobic gut bacteria are associated with stroke and post-stroke infection: a prospective case-control study. Transl Stroke Res 2021; 12(4): 581-92.
[http://dx.doi.org/10.1007/s12975-020-00863-4] [PMID: 33052545]
[234]
Matt SM, Allen JM, Lawson MA, Mailing LJ, Woods JA, Johnson RW. Butyrate and dietary soluble fiber improve neuroinflammation associated with aging in mice. Front Immunol 2018; 9: 1832.
[http://dx.doi.org/10.3389/fimmu.2018.01832] [PMID: 30154787]
[235]
Zhou Z, Xu N, Matei N, et al. Sodium butyrate attenuated neuronal apoptosis via GPR41/Gβγ/PI3K/Akt pathway after MCAO in rats. J Cereb Blood Flow Metab 2021; 41(2): 267-81.
[http://dx.doi.org/10.1177/0271678X20910533] [PMID: 32151222]
[236]
Fanaei H, Karimian SM, Sadeghipour HR, et al. Testosterone enhances functional recovery after stroke through promotion of antioxidant defenses, BDNF levels and neurogenesis in male rats. Brain Res 2014; 1558: 74-83.
[http://dx.doi.org/10.1016/j.brainres.2014.02.028] [PMID: 24565925]
[237]
Harada S, Fujita-Hamabe W, Tokuyama S. Ameliorating effect of hypothalamic brain-derived neurotrophic factor against impaired glucose metabolism after cerebral ischemic stress in mice. J Pharmacol Sci 2012; 118(1): 109-16.
[http://dx.doi.org/10.1254/jphs.11164FP]
[238]
Yang Y, Zhang X, Cui H, Zhang C, Zhu C, Li L. Apelin-13 protects the brain against ischemia/reperfusion injury through activating PI3K/Akt and ERK1/2 signaling pathways. Neurosci Lett 2014; 568: 44-9.
[http://dx.doi.org/10.1016/j.neulet.2014.03.037] [PMID: 24686182]
[239]
Liu J, Sun J, Wang F, et al. Neuroprotective Effects of Clostridium butyricum against vascular dementia in mice via metabolic butyrate. BioMed Res Int 2015; 2015: 1-12.
[http://dx.doi.org/10.1155/2015/412946] [PMID: 26523278]
[240]
Zhang H, Meng J, Yu H. Trimethylamine n-oxide supplementation abolishes the cardioprotective effects of voluntary exercise in mice fed a western diet. Front Physiol 2017; 8: 944.
[http://dx.doi.org/10.3389/fphys.2017.00944] [PMID: 29218015]
[241]
Wang Z, Roberts AB, Buffa JA, et al. Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis. Cell 2015; 163(7): 1585-95.
[http://dx.doi.org/10.1016/j.cell.2015.11.055] [PMID: 26687352]
[242]
Chen J, Guo Y, Gui Y, Xu D. Physical exercise, gut, gut microbiota, and atherosclerotic cardiovascular diseases. Lipids Health Dis 2018; 17(1): 17.
[http://dx.doi.org/10.1186/s12944-017-0653-9] [PMID: 29357881]
[243]
Qiu-Jun W, Yue-E S, Xin W, et al. Concomitant memantine and Lactobacillus plantarum treatment attenuates cognitive impairments in APP/PS1 mice. Aging 2021; 12(1): 628-49.
[244]
Liu J, Zhang T, Wang Y, et al. Baicalin ameliorates neuropathology in repeated cerebral ischemia-reperfusion injury model mice by remodeling the gut microbiota. Aging (Albany NY) 2020; 12(4): 3791-806.
[http://dx.doi.org/10.18632/aging.102846] [PMID: 32084011]
[245]
Li L, Chen B, Zhu R, et al. Fructus Ligustri Lucidi preserves bone quality through the regulation of gut microbiota diversity, oxidative stress, TMAO and Sirt6 levels in aging mice. Aging (Albany NY) 2019; 11(21): 9348-68.
[http://dx.doi.org/10.18632/aging.102376] [PMID: 31715585]
[246]
Guo Q, Ni C, Li L, et al. Integrated traditional chinese medicine improves functional outcome in acute ischemic stroke: From clinic to mechanism exploration with gut microbiota. Front Cell Infect Microbiol 2022; 12: 827129.
[http://dx.doi.org/10.3389/fcimb.2022.827129] [PMID: 35223549]
[247]
Guo Q, Jiang X, Ni C, et al. Gut microbiota-related effects of tanhuo decoction in acute ischemic stroke. Oxid Med Cell Longev 2021; 2021: 1-18.
[http://dx.doi.org/10.1155/2021/5596924] [PMID: 34136066]

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