Skip to main content

Advertisement

SpringerLink
Log in

Matrix Metalloproteinase-Mediated Neuroinflammation in Vascular Cognitive Impairment of the Binswanger Type

  • Review Paper
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Vascular cognitive impairment (VCI) is a heterogeneous group of diseases linked together by cerebrovascular disease. Treatment of VCI has been hindered by the lack of a coherent pathophysiological process that could provide molecular targets. Of the several forms of VCI, the small vessel disease form is both the most prevalent and generally has a progressive course. Binswanger’s disease (BD) is the small vessel form of VCI that involves extensive injury to the deep white matter. Growing evidence suggests that there is disruption of the blood–brain barrier (BBB) secondary to an inflammatory state. Matrix metalloproteinases (MMPs) are increased in the brain and CSF of patients with BD, and have been shown to disrupt the BBB in animal studies, suggesting that they may be biomarkers and therapeutic targets. Multimodal biomarkers derived from clinical, neuropsychological, imaging, and biochemical data can be used to narrow the VCI population to the progressive inflammatory form that will be optimal for treatment trials. This review describes the role of the MMPs in pathophysiology and their use as biomarkers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Adair JC, Charlie J, Dencoff JE, Kaye JA, Quinn JF, Camicioli RM, Stetler-Stevenson WG, Rosenberg GA (2004) Measurement of gelatinase B (MMP-9) in the cerebrospinal fluid of patients with vascular dementia and Alzheimer disease. Stroke 35:e159–e162

    Article  CAS  PubMed  Google Scholar 

  • Andin U, Gustafson L, Passant U, Brun A (2005) A clinico-pathological study of heart and brain lesions in vascular dementia. Dement Geriatr Cogn Disord 19:222–228

    Article  PubMed  Google Scholar 

  • Babikian V, Ropper AH (1987) Binswanger’s disease: a review. Stroke 18:2–12

    Article  CAS  PubMed  Google Scholar 

  • Bennett DA, Wilson RS, Gilley DW, Fox JH (1990) Clinical diagnosis of Binswanger’s disease [see comments]. J Neurol Neurosurg Psychiatry 53:961–965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bjerke M, Zetterberg H, Edman A, Blennow K, Wallin A, Andreasson U (2011) Cerebrospinal fluid matrix metalloproteinases and tissue inhibitor of metalloproteinases in combination with subcortical and cortical biomarkers in vascular dementia and Alzheimer’s disease. J Alzheimers Dis 27:665–676

    CAS  PubMed  Google Scholar 

  • Bjerke M, Jonsson M, Nordlund A, Eckerstrom C, Blennow K, Zetterberg H, Pantoni L, Inzitari D, Schmidt R, Wallin A (2014) Cerebrovascular biomarker profile is related to white matter disease and ventricular dilation in a LADIS substudy. Dement Geriatr Cogn Disord Extra 4:385–394

    Article  Google Scholar 

  • Blennow K, Wallin A, Fredman P, Karlsson I, Gottfries CG, Svennerholm L (1990) Blood-brain barrier disturbance in patients with Alzheimer’s disease is related to vascular factors. Acta Neurol Scand 81:323–326

    Article  CAS  PubMed  Google Scholar 

  • Brew K, Nagase H (2010) The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity. Biochim Biophys Acta 1803:55–71

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brooks WM, Wesley MH, Kodituwakku PW, Garry PJ, Rosenberg GA (1997) 1H-MRS differentiates white matter hyperintensities in subcortical arteriosclerotic encephalopathy from those in normal elderly. Stroke 28:1940–1943

    Article  CAS  PubMed  Google Scholar 

  • Cammer W, Bloom BR, Norton WT, Gordon S (1978) Degradation of basic protein in myelin by neutral proteases secreted by stimulated macrophages: a possible mechanism of inflammatory demyelination. Proc Natl Acad Sci USA 75:1554–1558

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Candelario-Jalil E, Yang Y, Rosenberg GA (2009) Diverse roles of matrix metalloproteinases and tissue inhibitors of metalloproteinases in neuroinflammation and cerebral ischemia. Neuroscience 158:983–994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Candelario-Jalil E, Thompson J, Taheri S, Grossetete M, Adair JC, Edmonds E, Prestopnik J, Wills J, Rosenberg GA (2011) Matrix metalloproteinases are associated with increased blood-brain barrier opening in vascular cognitive impairment. Stroke 42:1345–1350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caplan LR (1995) Binswanger’s disease–revisited. [Review]. Neurology 45:626–633

    Article  CAS  PubMed  Google Scholar 

  • Caplan LR, Schoene WC (1978) Clinical features of subcortical arteriosclerotic encephalopathy (Binswanger disease). Neurology 28:1206–1215

    Article  CAS  PubMed  Google Scholar 

  • Chandler S, Coates R, Gearing A, Lury J, Wells G, Bone E (1995) Matrix metalloproteinases degrade myelin basic protein. Neurosci Lett 201:223–226

    Article  CAS  PubMed  Google Scholar 

  • De Reuck J, Crevits L, De Coster W, Sieben G, vander Eecken H (1980) Pathogenesis of Binswanger chronic progressive subcortical encephalopathy. Neurology 30:920–928

    Article  PubMed  Google Scholar 

  • Erkinjuntti T, Roman G, Gauthier S, Feldman H, Rockwood K (2004) Emerging therapies for vascular dementia and vascular cognitive impairment. Stroke 35:1010–1017

    Article  CAS  PubMed  Google Scholar 

  • Fisher CM (1989) Binswanger’s encephalopathy: a review. J Neurol 236:65–79

    Article  CAS  PubMed  Google Scholar 

  • Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, Launer LJ, Laurent S, Lopez OL, Nyenhuis D et al (2011) Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42:2672–2713

    Article  PubMed  PubMed Central  Google Scholar 

  • Hachinski VC (1991) Multi-infarct dementia: a reappraisal. [Review]. Alzheimer Dis Assoc Disord 5:64–68

    Article  CAS  PubMed  Google Scholar 

  • Hanyu H, Asano T, Tanaka Y, Iwamoto T, Takasaki M, Abe K (2002) Increased blood-brain barrier permeability in white matter lesions of Binswanger’s disease evaluated by contrast-enhanced MRI. Dement Geriatr Cogn Disord 14:1–6

    Article  PubMed  Google Scholar 

  • Hawkins KE, DeMars KM, Yang C, Rosenberg GA, Candelario-Jalil E (2013) Fluorometric immunocapture assay for the specific measurement of matrix metalloproteinase-9 activity in biological samples: application to brain and plasma from rats with ischemic stroke. Mol Brain 6:14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jalal FY, Yang Y, Thompson J, Lopez AC, Rosenberg GA (2012) Myelin loss associated with neuroinflammation in hypertensive rats. Stroke 43:1115–1122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kantarci K, Senjem ML, Avula R, Zhang B, Samikoglu AR, Weigand SD, Przybelski SA, Edmonson HA, Vemuri P, Knopman DS et al (2011) Diffusion tensor imaging and cognitive function in older adults with no dementia. Neurology 77:26–34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liuzzi GM, Trojano M, Fanelli M, Avolio C, Fasano A, Livrea P, Riccio P (2002) Intrathecal synthesis of matrix metalloproteinase-9 in patients with multiple sclerosis: implication for pathogenesis. Mult Scler 8:222–228

    Article  CAS  PubMed  Google Scholar 

  • Maillard P, Seshadri S, Beiser A, Himali JJ, Au R, Fletcher E, Carmichael O, Wolf PA, DeCarli C (2012) Effects of systolic blood pressure on white-matter integrity in young adults in the Framingham Heart Study: a cross-sectional study. Lancet Neurol 11:1039–1047

    Article  PubMed  PubMed Central  Google Scholar 

  • Maillard P, Carmichael O, Harvey D, Fletcher E, Reed B, Mungas D, DeCarli C (2013) FLAIR and diffusion MRI signals are independent predictors of white matter hyperintensities. AJNR 34:54–61

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maniega SM, Valdes Hernandez MC, Clayden JD, Royle NA, Murray C, Morris Z, Aribisala BS, Gow AJ, Starr JM, Bastin ME et al (2015) White matter hyperintensities and normal-appearing white matter integrity in the aging brain. Neurobiol Aging 36:909–918

    Article  PubMed  PubMed Central  Google Scholar 

  • Nakaji K, Ihara M, Takahashi C, Itohara S, Noda M, Takahashi R, Tomimoto H (2006) Matrix metalloproteinase-2 plays a critical role in the pathogenesis of white matter lesions after chronic cerebral hypoperfusion in rodents. Stroke 37:2816–2823

    Article  CAS  PubMed  Google Scholar 

  • Nitkunan A, Charlton RA, McIntyre DJ, Barrick TR, Howe FA, Markus HS (2008) Diffusion tensor imaging and MR spectroscopy in hypertension and presumed cerebral small vessel disease. Magn Reson Med 59:528–534

    Article  CAS  PubMed  Google Scholar 

  • O’Brien JT, Erkinjuntti T, Reisberg B, Roman G, Sawada T, Pantoni L, Bowler JV, Ballard C, DeCarli C, Gorelick PB et al (2003) Vascular cognitive impairment. Lancet Neurol 2:89–98

    Article  PubMed  Google Scholar 

  • O’Sullivan M, Morris RG, Huckstep B, Jones DK, Williams SC, Markus HS (2004) Diffusion tensor MRI correlates with executive dysfunction in patients with ischaemic leukoaraiosis. J Neurol Neurosurg Psychiatry 75:441–447

    Article  PubMed  PubMed Central  Google Scholar 

  • Rigsby CS, Pollock DM, Dorrance AM (2007) Spironolactone improves structure and increases tone in the cerebral vasculature of male spontaneously hypertensive stroke-prone rats. Microvasc Res 73:198–205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rivera S, Khrestchatisky M, Kaczmarek L, Rosenberg GA, Jaworski DM (2010) Metzincin proteases and their inhibitors: foes or friends in nervous system physiology? J Neurosci 30:15337–15357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roman GC, Erkinjuntti T, Wallin A, Pantoni L, Chui HC (2002) Subcortical ischaemic vascular dementia. Lancet Neurol 1:426–436

    Article  PubMed  Google Scholar 

  • Roman GC, Salloway S, Black SE, Royall DR, Decarli C, Weiner MW, Moline M, Kumar D, Schindler R, Posner H (2010) Randomized, placebo-controlled, clinical trial of donepezil in vascular dementia: differential effects by hippocampal size. Stroke 41:1213–1221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rosenberg GA (2009) Matrix metalloproteinases and their multiple roles in neurodegenerative diseases. Lancet Neurol 8:205–216

    Article  CAS  PubMed  Google Scholar 

  • Rosenberg GA, Kornfeld M, Stovring J, Bicknell JM (1979) Subcortical arteriosclerotic encephalopathy (Binswanger): computerized tomography. Neurology 29:1102–1106

    Article  CAS  PubMed  Google Scholar 

  • Rosenberg GA, Prestopnik J, Adair JC, Huisa BN, Knoefel J, Caprihan A, Gasparovic C, Thompson J, Erhardt EB, Schrader R (2015) Validation of biomarkers in subcortical ischaemic vascular disease of the Binswanger type: approach to targeted treatment trials. J Neurol Neurosurg Psychiatry 12:1324–1330

    Article  Google Scholar 

  • Sappey Marinier D, Calabrese G, Hetherington HP, Fisher SN, Deicken R, Van Dyke C, Fein G, Weiner MW (1992) Proton magnetic resonance spectroscopy of human brain: applications to normal white matter, chronic infarction, and MRI white matter signal hyperintensities. Magn Reson Med 26:313–327

    Article  CAS  PubMed  Google Scholar 

  • Schneider JA, Arvanitakis Z, Bang W, Bennett DA (2007) Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology 69:2197–2204

    Article  PubMed  Google Scholar 

  • Smith EE, Schneider JA, Wardlaw JM, Greenberg SM (2012) Cerebral microinfarcts: the invisible lesions. Lancet Neurol 11:272–282

    Article  PubMed  PubMed Central  Google Scholar 

  • Sonnen JA, Santa Cruz K, Hemmy LS, Woltjer R, Leverenz JB, Montine KS, Jack CR, Kaye J, Lim K, Larson EB et al (2011) Ecology of the aging human brain. Arch Neurol 68:1049–1056

    Article  PubMed  PubMed Central  Google Scholar 

  • Sood R, Yang Y, Taheri S, Candelario-Jalil E, Estrada EY, Walker EJ, Thompson J, Rosenberg GA (2009) Increased apparent diffusion coefficients on MRI linked with matrix metalloproteinases and edema in white matter after bilateral carotid artery occlusion in rats. J Cereb Blood Flow Metab 29:308–316

    Article  CAS  PubMed  Google Scholar 

  • Strongin AY, Collier I, Bannikov G, Marmer BL, Grant GA, Goldberg GI (1995) Mechanism of cell surface activation of 72-kDa type IV collagenase. Isolation of the activated form of the membrane metalloprotease. J Biol Chem 270:5331–5338

    Article  CAS  PubMed  Google Scholar 

  • Taheri S, Gasparovic C, Huisa BN, Adair JC, Edmonds E, Prestopnik J, Grossetete M, Shah NJ, Wills J, Qualls C et al (2011) Blood-brain barrier permeability abnormalities in vascular cognitive impairment. Stroke 42:2158–2163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Toledo JB, Arnold SE, Raible K, Brettschneider J, Xie SX, Grossman M, Monsell SE, Kukull WA, Trojanowski JQ (2013) Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Centre. Brain 136:2697–2706

    Article  PubMed  PubMed Central  Google Scholar 

  • Topakian R, Barrick TR, Howe FA, Markus HS (2010) Blood-brain barrier permeability is increased in normal-appearing white matter in patients with lacunar stroke and leucoaraiosis. J Neurol Neurosurg Psychiatry 81:192–197

    Article  CAS  PubMed  Google Scholar 

  • Wallin A, Blennow K, Fredman P, Gottfries CG, Karlsson I, Svennerholm L (1990) Blood brain barrier function in vascular dementia. Acta Neurol Scand 81:318–322

    Article  CAS  PubMed  Google Scholar 

  • Wardlaw JM, Doubal FN, Valdes-Hernandez M, Wang X, Chappell FM, Shuler K, Armitage PA, Carpenter TC, Dennis MS (2013) Blood-brain barrier permeability and long-term clinical and imaging outcomes in cerebral small vessel disease. Stroke 44:525–527

    Article  PubMed  Google Scholar 

  • Yang Y, Estrada EY, Thompson JF, Liu W, Rosenberg GA (2007) Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat. J Cereb Blood Flow Metab 27:697–709

    CAS  PubMed  Google Scholar 

  • Yang Y, Thompson JF, Taheri S, Salayandia VM, McAvoy TA, Hill JW, Yang Y, Estrada EY, Rosenberg GA (2013) Early inhibition of MMP activity in ischemic rat brain promotes expression of tight junction proteins and angiogenesis during recovery. J Cereb Blood Flow Metab 33:1104–1114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yonas H, Gur D, Good BC, Latchaw RE, Wolfson SK Jr, Good WF, Maitz GS, Colsher JG, Barnes JE, Colliander KG et al (1985) Stable xenon CT blood flow mapping for evaluation of patients with extracranial-intracranial bypass surgery. J Neurosurg 62:324–333

    Article  CAS  PubMed  Google Scholar 

  • Yong VW (2005) Metalloproteinases: mediators of pathology and regeneration in the CNS. Nat Rev Neurosci 6:931–944

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The study was supported by Funding from NIH (RO1 NS052305-07), the US-Israeli Binational Foundation, and Bayer Pharmaceutical Corp (GR), and the University of New Mexico NIH National Center for Advancing Translational Sciences (UL1 TR000041).

Author information

Authors and Affiliations

  1. Departments of Neurology, Neurosciences, Cell Biology and Physiology, and Mathematics and Statistics, Health Sciences Center, University of New Mexico, Albuquerque, NM, 87107, USA

    Gary A. Rosenberg

Authors
  1. Gary A. Rosenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gary A. Rosenberg.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rosenberg, G.A. Matrix Metalloproteinase-Mediated Neuroinflammation in Vascular Cognitive Impairment of the Binswanger Type. Cell Mol Neurobiol 36, 195–202 (2016). https://doi.org/10.1007/s10571-015-0277-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-015-0277-4

Keywords

Search

Navigation