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Licensed Unlicensed Requires Authentication Published by De Gruyter October 13, 2015

Molecular mechanisms of estrogen for neuroprotection in spinal cord injury and traumatic brain injury

  • Mrinmay Chakrabarti , Arabinda Das , Supriti Samantaray , Joshua A. Smith , Naren L. Banik , Azizul Haque and Swapan K. Ray EMAIL logo

Abstract

Estrogen (EST) is a steroid hormone that exhibits several important physiological roles in the human body. During the last few decades, EST has been well recognized as an important neuroprotective agent in a variety of neurological disorders in the central nervous system (CNS), such as spinal cord injury (SCI), traumatic brain injury (TBI), Alzheimer’s disease, and multiple sclerosis. The exact molecular mechanisms of EST-mediated neuroprotection in the CNS remain unclear due to heterogeneity of cell populations that express EST receptors (ERs) in the CNS as well as in the innate and adaptive immune system. Recent investigations suggest that EST protects the CNS from injury by suppressing pro-inflammatory pathways, oxidative stress, and cell death, while promoting neurogenesis, angiogenesis, and neurotrophic support. In this review, we have described the currently known molecular mechanisms of EST-mediated neuroprotection and neuroregeneration in SCI and TBI. At the same time, we have emphasized on the recent in vitro and in vivo findings from our and other laboratories, implying potential clinical benefits of EST in the treatment of SCI and TBI.


Corresponding author: Swapan K. Ray, Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC 29209, USA, e-mail:

Acknowledgments

This work was supported in part by grants from South Carolina Spinal Cord Injury Research Fund (SC SCIRF, Columbia, SC, USA) and University of South Carolina School of Medicine Research Development Fund (USC SOM RDF, Columbia, SC, USA).

References

Asl, S.Z., Khaksari, M., Khachki, A.S., Shahrokhi, N., and Nourizade, S. (2013). Contribution of estrogen receptors α and β in the brain response to traumatic brain injury. J. Neurosurg. 119, 353–361.10.3171/2013.4.JNS121636Search in Google Scholar

Azevedo, R.B., Lacava, Z.G., Miyasaka, C.K., Chaves, S.B., and Curi, R. (2001). Regulation of antioxidant enzyme activities in male and female rat macrophages by sex steroids. Braz. J. Med. Biol. Res. 34, 683–687.10.1590/S0100-879X2001000500018Search in Google Scholar

Baker, K.A. and Hagg, T. (2005). An adult rat spinal cord contusion model of sensory axon degeneration: the estrus cycle or a preconditioning lesion do not affect outcome. J. Neurotrauma 22, 415–428.10.1089/neu.2005.22.415Search in Google Scholar

Ball, L.J., Levy, N., Zhao, X., Griffin, C., Tagliaferri, M., Cohen, I., Ricke, W.A., Speed, T.P., Firestone, G.L., and Leitman, D.C. (2009). Cell type- and estrogen receptor-subtype specific regulation of selective estrogen receptor modulator regulatory elements. Mol. Cell Endocrinol. 299, 204–211.10.1016/j.mce.2008.10.050Search in Google Scholar

Bayir, H., Marion, D.W., Puccio, A.M., Wisniewski, S.R., Janesko, K.L., Clark, R.S., and Kochanek, P.M. (2004). Marked gender effect on lipid peroxidation after severe traumatic brain injury in adult patients. J. Neurotrauma 21, 1–8.10.1089/089771504772695896Search in Google Scholar

Beal, M.F. (1998). Mitochondrial dysfunction in neurodegenerative diseases. Biochim. Biophys. Acta 1366, 211–223.10.1016/S0005-2728(98)00114-5Search in Google Scholar

Behl, C., Widmann, M., Trapp, T., and Holsboer, F. (1995). 17-β Estradiol protects neurons from oxidative stress-induced cell death in vitro. Biochem. Biophys. Res. Commun. 216, 473–482.10.1006/bbrc.1995.2647Search in Google Scholar

Behl, C., Skutella, T., Lezoualc’h, F., Post, A., Widmann, M., Newton, C.J., and Holsboer, F. (1997). Neuroprotection against oxidative stress by estrogens: structure–activity relationship. Mol. Pharmacol. 51, 535–541.10.1124/mol.51.4.535Search in Google Scholar

Behl, C., Moosmann, B., Manthey, D., and Heck, S. (2000). The female sex hormone oestrogen as neuroprotectant: activities at various levels. Novartis Found. Symp. 230, 221–234.10.1002/0470870818.ch16Search in Google Scholar

Borras, C., Sastre, J., Garcia-Sala, D., Lloret, A., Pallardo, F.V., and Vina, J. (2003). Mitochondria from females exhibit higher antioxidant gene expression and lower oxidative damage than males. Free Radic. Biol. Med. 34, 546–552.10.1016/S0891-5849(02)01356-4Search in Google Scholar

Bramlett, H.M. and Dietrich, W.D. (2001). Neuropathological protection after traumatic brain injury in intact female rats versus males or ovariectomized females. J. Neurotrauma 18, 891–900.10.1089/089771501750451811Search in Google Scholar PubMed

Brinton, L.A., Richesson, D., Leitzmann, M.F., Gierach, G.L., Schatzkin, A., Mouw, T., Hollenbeck, A.R., and Lacey, J.V., Jr. (2008). Menopausal hormone therapy and breast cancer risk in the NIH-AARP Diet and Health Study Cohort. Cancer Epidemiol. Biomarkers Prev. 17, 3150–3160.10.1158/1055-9965.EPI-08-0435Search in Google Scholar PubMed PubMed Central

Caliceti, C., Aquila, G., Pannella, M., Morelli, M.B., Fortini, C., Pinton, P., Bonora, M., Hrelia, S., Pannuti, A., Miele, L., et al. (2013). 17β-Estradiol enhances signalling mediated by VEGF-A-δ-like ligand 4-notch1 axis in human endothelial cells. PLoS One 8, e71440.10.1371/journal.pone.0071440Search in Google Scholar PubMed PubMed Central

Chakrabarti, S., Lekontseva, O., and Davidge, S.T. (2008). Estrogen is a modulator of vascular inflammation. IUBMB Life 60, 376–382.10.1002/iub.48Search in Google Scholar PubMed

Chakrabarti, M., Banik, N.L., and Ray, S.K. (2014a). miR-7-1 potentiated estrogen receptor agonists for functional neuroprotection in VSC4.1 motoneurons. Neuroscience 256, 322–333.10.1016/j.neuroscience.2013.10.027Search in Google Scholar PubMed PubMed Central

Chakrabarti, M., Haque, A., Banik, N.L., Nagarkatti, P., Nagarkatti, M., and Ray, S.K. (2014b). Estrogen receptor agonists for attenuation of neuroinflammation and neurodegeneration. Brain Res. Bull. 109, 22–31.10.1016/j.brainresbull.2014.09.004Search in Google Scholar PubMed PubMed Central

Chaovipoch, P., Jelks, K.A., Gerhold, L.M., West, E.J., Chongthammakun, S., and Floyd, C.L. (2006). 17β-Estradiol is protective in spinal cord injury in post- and pre-menopausal rats. J. Neurotrauma 23, 830–852.10.1089/neu.2006.23.830Search in Google Scholar PubMed

Chen, S., Nilsen, J., and Brinton, R.D. (2006). Dose and temporal pattern of estrogen exposure determines neuroprotective outcome in hippocampal neurons: therapeutic implications. Endocrinology 147, 5303–5313.10.1210/en.2006-0495Search in Google Scholar PubMed

Chen, G., Zhang, S., Shi, J., Ai, J., Qi, M., and Hang, C. (2009a). Simvastatin reduces secondary brain injury caused by cortical contusion in rats: possible involvement of TLR4/NF-κB pathway. Exp. Neurol. 216, 398–406.10.1016/j.expneurol.2008.12.019Search in Google Scholar PubMed

Chen, S.H., Chang, C.Y., Chang, H.K., Chen, W.C., Lin, M.T., Wang, J.J., Chen, J.C., and Chang, F.M. (2009b). Premarin stimulates estrogen receptor-α to protect against traumatic brain injury in male rats. Crit. Care Med. 37, 3097–3106.10.1097/CCM.0b013e3181bc7986Search in Google Scholar PubMed

Conti, A., Gulì, C., La Torre, D., Tomasello, C., Angileri, F.F., and Aguennouz, M. (2010). Role of inflammation and oxidative stress mediators in gliomas. Cancers (Basel) 2, 693–712.10.3390/cancers2020693Search in Google Scholar PubMed PubMed Central

Cuzzocrea, S., Genovese, T., Mazzon, E., Esposito, E., Di Paola, R., Muià, C., Crisafulli, C., Peli, A., Bramanti, P., and Chaudry, I.H. (2008). Effect of 17β-estradiol on signal transduction pathways and secondary damage in experimental spinal cord trauma. Shock 29, 362–371.10.1097/SHK.0b013e31814545dcSearch in Google Scholar PubMed

Das, A., Sribnick, E.A., Wingrave, J.M., Del Re, A.M., Woodward, J.J., Appel, S.H., Banik, N.L., and Ray, S.K. (2005). Calpain activation in apoptosis of ventral spinal cord 4.1 (VSC4.1) motoneurons exposed to glutamate: calpain inhibition provides functional neuroprotection. J. Neurosci. Res. 81, 551–562.10.1002/jnr.20581Search in Google Scholar PubMed

Das, A., Smith, J.A., Gibson, C., Varma, A.K., Ray, S.K., and Banik, N.L. (2011). Estrogen receptor agonists and estrogen attenuate TNF-α-induced apoptosis in VSC4.1 motoneurons. J. Endocrinol. 208, 171–182.10.1677/JOE-10-0338Search in Google Scholar PubMed PubMed Central

Deroo, B.J. and Buensuceso, A.V. (2010). Minireview. Estrogen receptor-β: mechanistic insights from recent studies. Mol. Endocrinol. 24, 1703–1714.10.1210/me.2009-0288Search in Google Scholar PubMed PubMed Central

Dimayuga, F.O., Reed, J.L., Carnero, G.A., Wang, C., Dimayuga, E.R., Dimayuga, V.M., Perger, A., Wilson, M.E., Keller, J.N., and Bruce-Keller, A.J. (2005). Estrogen and brain inflammation: effects on microglial expression of MHC, costimulatory molecules and cytokines. J. Neuroimmunol. 16, 123–136.10.1016/j.jneuroim.2004.12.016Search in Google Scholar PubMed

Doperalski, N.J., Sandhu, M.S., Bavis, R.W., Reier, P.J., and Fuller, D.D. (2008). Ventilation and phrenic output following high cervical spinal hemisection in male vs. female rats. Respir. Physiol. Neurobiol. 162, 160–167.10.1016/j.resp.2008.06.005Search in Google Scholar PubMed PubMed Central

Doshi, S.B. and Agarwal, A. (2013). The role of oxidative stress in menopause. J. Midlife Health 4, 140–146.Search in Google Scholar

Dubal, D.B., Kashon, M.L., Pettigrew, L.C., Ren, J.M., Finklestein, S.P., Rau, S.W., and Wise, P.M. (1998). Estradiol protects against ischemic injury. J. Cereb. Blood Flow Metab. 18, 1253–1258.10.1097/00004647-199811000-00012Search in Google Scholar PubMed

Dubal, D.B., Shughrue, P.J., Wilson, M.E., Merchenthaler, I., and Wise, P.M. (1999). Estradiol modulates bcl-2 in cerebral ischemia: a potential role for estrogen receptors. J. Neurosci. 19, 6385–6393.10.1523/JNEUROSCI.19-15-06385.1999Search in Google Scholar

Dubal, D.B., Zhu, H., Yu, J., Rau, S.W., Shughrue, P.J., Merchenthaler, I., Kindy, M.S., and Wise, P.M. (2001). Estrogen receptor a, not b, is a critical link in estradiol-mediated protection against brain injury. Proc. Natl. Acad. Sci. USA 98, 1952–1957.10.1073/pnas.98.4.1952Search in Google Scholar PubMed PubMed Central

Endoh, H., Sasaki, H., Maruyama, K., Takeyama, K., Waga, I., Shimizu, T., Kato, S., and Kawashima, H. (1997). Rapid activation of MAP kinase by estrogen in the bone cell line. Biochem. Biophys. Res. Commun. 235, 99–102.10.1006/bbrc.1997.6746Search in Google Scholar

Enmark, E., Pelto-Huikko, M., Grandien, K., Lagercrantz, S., Lagercrantz, J., Fried, G., Nordenskjöld, M., and Gustafsson, J.A. (1997). Human estrogen receptor β-gene structure, chromosomal localization, and expression pattern. J. Clin. Endocrinol. Metab. 82, 4258–4265.10.1210/jc.82.12.4258Search in Google Scholar

Farooque, M., Suo, Z., Arnold, P.M., Wulser, M.J., Chou, C.T., Vancura, R.W., Fowler, S., and Festoff, B.W. (2006). Gender-related differences in recovery of locomotor function after spinal cord injury in mice. Spinal Cord 44, 182–187.10.1038/sj.sc.3101816Search in Google Scholar

Filardo, E.J., Quinn, J.A., Bland, K.I., and Frackelton, A.R., Jr. (2000). Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF. Mol. Endocrinol. 14, 1649–1660.10.1210/mend.14.10.0532Search in Google Scholar

Gatson, J.W., Maass, D.L., Simpkins, J.W., Idris, A.H., Minei, J.P., and Wigginton, J.G. (2009). Estrogen treatment following severe burn injury reduces brain inflammation and apoptotic signaling. J. Neuroinflammation 6, 30.10.1186/1742-2094-6-30Search in Google Scholar

Gatson, J.W., Simpkins, J.W., Yi, K.D., Idris, A.H., Minei, J.P., and Wigginton, J.G. (2011). Aromatase is increased in astrocytes in the presence of elevated pressure. Endocrinology 152, 207–213.10.1210/en.2010-0724Search in Google Scholar

Gatson, J.W., Liu, M.M., Abdelfattah, K., Wigginton, J.G., Smith, S., Wolf, S., Simpkins, J.W., and Minei, J.P. (2012). Estrone is neuroprotective in rats after traumatic brain injury. J. Neurotrauma 29, 2209–2219.10.1089/neu.2011.2274Search in Google Scholar

Gottipati, S. and Cammarata, P.R. (2008). Mitochondrial superoxide dismutase activation with 17β-estradiol-treated human lens epithelial cells. Mol. Vis. 14, 898–905.Search in Google Scholar

Greb, R.R., Heikinheimo, O., Williams, R.F., Hodgen, G.D., and Goodman, A.L. (1997). Vascular endothelial growth factor in primate endometrium is regulated by oestrogen-receptor and progesterone-receptor ligands in vivo. Hum. Reprod. 12, 1280–1292.10.1093/humrep/12.6.1280Search in Google Scholar

Green, P.S. and Simpkins, J.W. (2000). Neuroprotective effects of estrogens: potential mechanisms of action. Int. J. Dev. Neurosci. 18, 347–358.10.1016/S0736-5748(00)00017-4Search in Google Scholar

Green, P.S., Gordon, K., and Simpkins, J.W. (1997). Phenolic A ring requirement for the neuroprotective. Effects of steroids. J. Steroid Biochem. Mol. Biol. 63, 229–235.10.1016/S0960-0760(97)00124-6Search in Google Scholar

Harris, H.A. (2007). Estrogen receptor-β: recent lessons from in vivo studies. Mol. Endocrinol. 21, 1–13.10.1210/me.2005-0459Search in Google Scholar

Hawk, T., Zhang, Y.Q., Rajakumar, G., Day, A.L., and Simpkins, J.W. (1998). Testosterone increases and estradiol decreases middle cerebral artery occlusion lesion size in male rats. Brain Res. 796, 296–298.10.1016/S0006-8993(98)00327-8Search in Google Scholar

Henderson, V.W. (1997). The epidemiology of estrogen replacement therapy and Alzheimer’s disease. Neurology 48, S27–S35.10.1212/WNL.48.5_Suppl_7.27SSearch in Google Scholar

Improta-Brears, T., Whorton, A.R., Codazzi, F., York, J.D., Meyer, T., and McDonnell, D.P. (1999). Estrogen-induced activation of mitogen-activated protein kinase requires mobilization of intracellular calcium. Proc. Natl. Acad. Sci. USA 96, 4686–4691.10.1073/pnas.96.8.4686Search in Google Scholar

Kabadi, S.V., Stoica, B.A., Byrnes, K.R., Hanscom, M., Loane, D.J., and Faden, A.I. (2012). Selective CDK inhibitor limits neuroinflammation and progressive neurodegeneration after brain trauma. J. Cereb. Blood Flow Metab. 32, 137–149.10.1038/jcbfm.2011.117Search in Google Scholar

Kachadroka, S., Hall, A.M., Niedzielko, T.L., Chongthammakun, S., and Floyd, C.L. (2010). Effect of endogenous androgens on 17β-estradiol-mediated protection after spinal cord injury in male rats. J. Neurotrauma 27, 611–26.10.1089/neu.2009.1069Search in Google Scholar

Keller, J.N., Germeyer, A., Begley, J.G., and Mattson, M.P. (1997). 17β-Estradiol attenuates oxidative impairment of synaptic Na+/K+ ATPase activity, glucose transport, and glutamate transport induced by amyloid β-peptide and iron. J. Neurosci. Res. 50, 522–530.10.1002/(SICI)1097-4547(19971115)50:4<522::AID-JNR3>3.0.CO;2-GSearch in Google Scholar

Khalil, R.A. (2010). Potential approaches to enhance the effects of estrogen on senescent blood vessels and postmenopausal cardiovascular disease. Cardiovasc. Hematol. Agents Med. Chem. 8, 29–46.10.2174/187152510790796156Search in Google Scholar

Kim-Schulze, S., McGowan, K.A., Hubchak, S.C., Cid, M.C., Martin, M.B., Kleinman, H.K., Greene, G.J., and Schnaper, H.W. (1996). Expression of an estrogen receptor by human coronary artery and umbilical vein endothelial cells. Circulation 94, 1402–1407.10.1161/01.CIR.94.6.1402Search in Google Scholar

Kuiper, G.G., Enmark, E., Pelto-Huikko, M., Nilsson, S., and Gustafsson, J.A. (1996). Cloning of a novel receptor expressed in rat prostate and ovary. Proc. Natl. Acad. Sci. USA 93, 5925–5930.10.1073/pnas.93.12.5925Search in Google Scholar

Lahm, T., Crisostomo, P.R., Markel, T.A., Wang, M., Weil, B.R., Novotny, N.M., and Meldrum, D.R. (2008). The effects of estrogen on pulmonary artery vasoreactivity and hypoxic pulmonary vasoconstriction: potential new clinical implications for an old hormone. Crit. Care Med. 36, 2174–2183.10.1097/CCM.0b013e31817d1a92Search in Google Scholar

Lapanantasin, S., Chongthammakun, S., Floyd, C.L., and Berman, R.F. (2006). Effects of 17β-estradiol on intracellular calcium changes and neuronal survival after mechanical strain injury in neuronal-glial cultures. Synapse 60, 406–410.10.1002/syn.20308Search in Google Scholar

Le Romancer, M., Treilleux, I., Leconte, N., Robin-Lespinasse, Y., Sentis, S., Bouchekioua-Bouzaghou, K., Goddard, S., Gobert-Gosse, S., and Corbo, L. (2008). Regulation of estrogen rapid signaling through arginine methylation by PRMT1. Mol. Cell. 31, 212–221.10.1016/j.molcel.2008.05.025Search in Google Scholar

Levin, E.R. (2009). Plasma membrane estrogen receptors. Trends Endocrinol. Metab. 20, 477–482.10.1016/j.tem.2009.06.009Search in Google Scholar

Li, Y., Wang, S., Xia, Y., Wang, J., Pan, W., Shi, Y., and Wang, M. (2007). Neuroprotective effect of estrogen after chronic spinal cord injury in ovariectomized rats. Neural Regen. Res. 2, 471–474.10.1016/S1673-5374(07)60092-9Search in Google Scholar

Liu, W., Su, W., and Roberts, T.M. (1998). Discovery of estrogen-responsive genes using an improved method which combines subtractive hybridization and PCR. Nucleic Acids Res. 26, 3616–3618.10.1093/nar/26.15.3616Search in Google Scholar PubMed PubMed Central

López Rodríguez, A.B., Mateos Vicente, B., Romero-Zerbo, S.Y., Rodriguez-Rodriguez, N., Bellini, M.J., Rodriguez de Fonseca, F., Bermudez-Silva, F.J., Azcoitia, I., Garcia-Segura, L.M., and Viveros, M.P. (2011). Estradiol decreases cortical reactive astrogliosis after brain injury by a mechanism involving cannabinoid receptors. Cereb. Cortex 21, 2046–2055.10.1093/cercor/bhq277Search in Google Scholar PubMed

Marino, M., Galluzzo, P., and Ascenzi, P. (2006). Estrogen signaling multiple pathways to impact gene transcription. Curr. Genomics 7, 497–508.10.2174/138920206779315737Search in Google Scholar PubMed PubMed Central

Martinkovich, S., Shah, D., Planey, S.L., and Arnott, J.A. (2014). Selective estrogen receptor modulators: tissue specificity and clinical utility. Clin. Interv. Aging 9, 1437–1452.10.2147/CIA.S66690Search in Google Scholar PubMed PubMed Central

Mazzeo, A.T., Beat, A., Singh, A., and Bullock, M.R. (2009). The role of mitochondrial transition pore, and its modulation, in traumatic brain injury and delayed neurodegeneration after TBI. Exp. Neurol. 218, 363–370.10.1016/j.expneurol.2009.05.026Search in Google Scholar PubMed

Mbye, L.H., Singh, I.N., Sullivan, P.G., Springer, J.E., and Hall, E.D. (2008). Attenuation of acute mitochondrial dysfunction after traumatic brain injury in mice by NIM811, a non-immunosuppressive cyclosporin A analog. Exp. Neurol. 209, 243–253.10.1016/j.expneurol.2007.09.025Search in Google Scholar

McEwen, M.L., Sullivan, P.G., and Springer, J.E. (2007). Pretreatment with the cyclosporin derivative, NIM811, improves the function of synaptic mitochondria following spinal cord contusion in rats. J. Neurotrauma 24, 613–624.10.1089/neu.2006.9969Search in Google Scholar

McIntosh, T.K., Smith, D.H., Voddi, M., Perri, B.R., and Stutzmann, J.M. (1996). Riluzole, a novel neuroprotective agent, attenuates both neurologic motor and cognitive dysfunction following experimental brain injury in the rat. J. Neurotrauma 13, 767–780.10.1089/neu.1996.13.767Search in Google Scholar

Mittal, M., Siddiqui, M.R., Tran, K., Reddy, S.P., and Malik, A.B. (2014). Reactive oxygen species in inflammation and tissue injury. Antioxid. Redox Signal 20, 1126–1167.10.1089/ars.2012.5149Search in Google Scholar

Moosmann, B. and Behl, C. (1999). The antioxidant neuroprotective effects of estrogens and phenolic compounds are independent from their estrogenic properties. Proc. Natl. Acad. Sci. USA 96, 8867–8872.10.1073/pnas.96.16.8867Search in Google Scholar

Morales, D.E., McGowan, K.A., Grant, D.S., Maheshwari, S., Bhartiya, D., Cid, M.C., Kleinman, H.K., and Schnaper, H.W. (1995). Estrogen promotes angiogenic activity in human umbilical vein endothelial cells in vitro and in a murine model. Circulation 91, 755–763.10.1161/01.CIR.91.3.755Search in Google Scholar

Mosselman, S., Polman, J., and Dijkema, R. (1996). ERβ: identification and characterization of a novel human estrogen receptor. FEBS Lett. 392, 49–53.10.1016/0014-5793(96)00782-XSearch in Google Scholar

Murakoshi, M., Ikada, R., and Tagawa, M. (1999). Regulation of prostatic glutathione-peroxidase (GSH-PO) in rats treated with a combination of testosterone and 17β-estradiol. J. Toxicol. Sci. 24, 415–420.10.2131/jts.24.5_415Search in Google Scholar

Naderi, V., Khaksari, M., Abbasi, R., and Maghool, F. (2015). Estrogen provides neuroprotection against brain edema and blood brain barrier disruption through both estrogen receptors α and β following traumatic brain injury. Iran. J. Basic Med. Sci. 18, 138–144.Search in Google Scholar

Nilsen, J., Chen, S., and Brinton, R.D. (2002). Dual action of estrogen on glutamate-induced calcium signaling: mechanisms requiring interaction between estrogen receptors and src/mitogen activated protein kinase pathway. Brain Res. 930, 216–234.10.1016/S0006-8993(02)02254-0Search in Google Scholar

Paruthiyil, S., Cvoro, A., Zhao, X., Wu, Z., Sui, Y., Staub, R.E., Baggett, S., Herber, C.B., Griffin, C., Tagliaferri, M., et al. (2009). Drug and cell type-specific regulation of genes with different classes of estrogen receptor β-selective agonists. PLoS One 4, e6271.10.1371/journal.pone.0006271Search in Google Scholar PubMed PubMed Central

Ray, S.K., Karmakar, S., Nowak, M.W., and Banik N.L. (2006). Inhibition of calpain and caspase-3 prevented apoptosis and preserved electrophysiological properties of voltage-gated and ligand-gated ion channels in rat primary cortical neurons exposed to glutamate. Neuroscience 139, 577–595.10.1016/j.neuroscience.2005.12.057Search in Google Scholar PubMed

Ritz, M.F. and Hausmann, O.N. (2008). Effect of 17β-estradiol on functional outcome, release of cytokines, astrocyte reactivity and inflammatory spreading after spinal cord injury in male rats. Brain Res. 1203, 177–188.10.1016/j.brainres.2008.01.091Search in Google Scholar PubMed

Rong, W., Wang, J., Liu, X., Jiang, L., Wei, F., Zhou, H., Han, X., and Liu, Z. (2012). 17β-Estradiol attenuates neural cell apoptosis through inhibition of JNK phosphorylation in SCI rats and excitotoxicity induced by glutamate in vitro. Int. J. Neurosci. 122, 381–387.10.3109/00207454.2012.668726Search in Google Scholar PubMed

Saatman, K.E., Duhaime, A.C., Bullock, R., Maas, A.I., Valadka, A., and Manley, G.T. (2010). Workshop scientific team and advisory panel members. Classification of traumatic brain injury for targeted therapies. J. Neurotrauma 25, 719–738.10.1089/neu.2008.0586Search in Google Scholar PubMed PubMed Central

Sahuquillo, J. and Vilalta, A. (2007). Cooling the injured brain: how does moderate hypothermia influence the pathophysiology of traumatic brain injury. Curr. Pharm. Des. 13, 2310–2322.10.2174/138161207781368756Search in Google Scholar PubMed

Samantaray, S., Sribnick, E.A., Das, A., Thakore, N.P., Matzelle, D., Yu, S.P., Ray, S.K., Wei, L., and Banik, N.L. (2010). Neuroprotective efficacy of estrogen in experimental spinal cord injury in rats. Ann. NY Acad. Sci. 1199, 90–94.10.1111/j.1749-6632.2009.05357.xSearch in Google Scholar PubMed PubMed Central

Samantaray, S., Smith, J.A., Das, A., Matzelle, D.D., Varma, A.K., Ray, S.K., and Banik, N.L. (2011). Low dose estrogen prevents neuronal degeneration and microglial reactivity in an acute model of spinal cord injury: effect of dosing, route of administration, and therapy delay. Neurochem. Res. 36, 1809–18016.10.1007/s11064-011-0498-ySearch in Google Scholar PubMed PubMed Central

Schmidt, R., Fazekas, F., Reinhart, B., Kapeller, P., Fazekas, G., Offenbacher, H., Eber, B., Schumacher, M., and Freidl, W. (1996). Estrogen replacement therapy in older women: a neuropsychological and brain MRI study. J. Am. Geriatr. Soc. 44, 1307–1313.10.1111/j.1532-5415.1996.tb01400.xSearch in Google Scholar PubMed

Selvamani, A., Sathyan, P., Miranda, R.C., and Sohrabji, F. (2012). An antagomir to microRNA Let7f promotes neuroprotection in an ischemic stroke model. PLoS One 7, e32662.10.1371/journal.pone.0032662Search in Google Scholar PubMed PubMed Central

Seo, K.H., Ko, H.M., Choi, J.H., Jung, H.H., Chun, Y.H., Choi, I.W., Lee, H.K., and Im, S.Y. (2004). Essential role for platelet-activating factor-induced NF-κB activation in macrophage-derived angiogenesis. Eur. J. Immunol. 34, 2129–2137.10.1002/eji.200424957Search in Google Scholar PubMed

Singer, C.A., Figueroa-Masot, X.A., Batchelor, R.H., and Dorsa, D.M. (1999). The mitogen-activated protein kinase pathway mediates estrogen neuroprotection after glutamate toxicity in primary cortical neurons. J. Neurosci. 19, 2455–2463.10.1523/JNEUROSCI.19-07-02455.1999Search in Google Scholar

Singh, M., Jr., Setalo, G., Guan, X., Warren, M., and Toran-Allerand, C.D. (1999). Estrogen-induced activation of mitogen-activated protein kinase in cerebral cortical explants: convergence of estrogen and neurotrophin signaling pathways. J. Neurosci. 19, 1179–1188.10.1523/JNEUROSCI.19-04-01179.1999Search in Google Scholar

Smiley, D.A. and Khalil, R.A. (2009). Estrogenic compounds, estrogen receptors and vascular cell signaling in the aging blood vessels. Curr. Med. Chem. 16, 1863–1887.10.2174/092986709788186093Search in Google Scholar PubMed PubMed Central

Sribnick, E.A., Wingrave, J.M., Matzelle, D.D., Ray, S.K., and Banik, N.L. (2003). Estrogen as a neuroprotective agent in the treatment of spinal cord injury. Ann. NY Acad. Sci. 993, 125–133.10.1111/j.1749-6632.2003.tb07521.xSearch in Google Scholar PubMed

Sribnick, E.A., Ray, S.K., and Banik, N.L. (2004). Estrogen as a multi-active neuroprotective agent in traumatic injuries. Neurochem. Res. 29, 2007–2014.10.1007/s11064-004-6874-0Search in Google Scholar PubMed

Sribnick, E.A., Wingrave, J.M., Matzelle, D.D., Wilford, G.G., Ray, S.K., and Banik, N.L. (2005). Estrogen attenuated markers of inflammation and decreased lesion volume in acute spinal cord injury in rats. J. Neurosci. Res. 82, 283–293.10.1002/jnr.20622Search in Google Scholar PubMed

Sribnick, E.A., Matzelle, D.D., Ray, S.K., and Banik, N.L. (2006). Estrogen treatment of spinal cord injury attenuates calpain activation and apoptosis. J. Neurosci. Res. 84, 1064–1075.10.1002/jnr.21016Search in Google Scholar PubMed

Sribnick, E.A., Matzelle, D.D., Banik, N.L., and Ray, S.K. (2007). Direct evidence for calpain involvement in apoptotic death of neurons in spinal cord injury in rats and neuroprotection with calpain inhibitor. Neurochem. Res. 32, 2210–2216.10.1007/s11064-007-9433-7Search in Google Scholar PubMed

Sribnick, E.A., Del Re, A.M., Ray, S.K., Woodward, J.J., and Banik, N.L. (2009). Estrogen attenuates glutamate-induced cell death by inhibiting Ca2+ influx through L-type voltage-gated Ca2+ channels. Brain Res. 1276, 159–170.10.1016/j.brainres.2009.04.022Search in Google Scholar PubMed PubMed Central

Sribnick, E.A., Samantaray, S., Das, A., Smith, J., Matzelle, D.D., Ray, S.K., and Banik, N.L. (2010). Postinjury estrogen treatment of chronic spinal cord injury improves locomotor function in rats. J. Neurosci. Res. 88, 1738–1750.10.1002/jnr.22337Search in Google Scholar PubMed PubMed Central

Srivastava, S., Toraldo, G., Weitzmann, M.N., Cenci, S., Ross, F.P., and Pacifici, R. (2001). Estrogen decreases osteoclast formation by down-regulating receptor activator of NF-κB ligand (RANKL)-induced JNK activation. J. Biol. Chem. 276, 8836–8840.10.1074/jbc.M010764200Search in Google Scholar

Swartz, K.R., Fee, D.B., Joy, K.M., Roberts, K.N., Sun, S., Scheff, N.N., Wilson, M.E., and Scheff, S.W. (2007). Gender differences in spinal cord injury are not estrogen-dependent. J. Neurotrauma 24, 473–480.10.1089/neu.2006.0167Search in Google Scholar

Tang, M.X., Jacobs, D., Stern, Y., Marder, K., Schofield, P., Gurland, B., Andrews, H., and Mayeux, R. (1996). Effect of oestrogen during menopause on risk and age at onset of Alzheimer’s disease. Lancet 348, 429–432.10.1016/S0140-6736(96)03356-9Search in Google Scholar

Tremblay, G.B., Tremblay, A., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Labrie, F., and Giguère, V. (1997). Cloning, chromosomal localization, and functional analysis of the murine estrogen receptor β. Mol. Endocrinol. 11, 353–365.Search in Google Scholar

Tucker, L.T., Fu, A.H., and McCabe, J.T. (2015). Performance of male and female C57BL/6J mice on motor and cognitive tasks commonly used in pre-clinical traumatic brain injury research. J. Neurotrauma, in press.10.1089/neu.2015.3977Search in Google Scholar

Unnikrishnan, A.G. and Rajaratnam, S. (2000). An approach to postmenopausal osteoporosis. Natl. Med. J. India 13, 145–146.Search in Google Scholar

Varea, O., Arevalo, M.A., Garrido, J.J., Garcia-Segura, L.M., Wandosell, F., and Mendez, P. (2010). Interaction of estrogen receptors with insulin-like growth factor-I and Wnt signaling in the nervous system. Steroids 75, 565–569.10.1016/j.steroids.2009.09.006Search in Google Scholar

Varma, A.K., Das, A., Wallace, G., Barry, J., Vertegel, A.A., Ray, S.K., and Banik, N.L. (2013). Spinal cord injury: a review of current therapy, future treatments, and basic science frontiers. Neurochem. Res. 38, 895–905.10.1007/s11064-013-0991-6Search in Google Scholar

Vegeto, E., Benedusi, V., and Maggi, A. (2008). Estrogen anti-inflammatory activity in brain: a therapeutic opportunity for menopause and neurodegenerative diseases. Front. Neuroendocrinol. 29, 507–519.10.1016/j.yfrne.2008.04.001Search in Google Scholar

Venkov, C.D., Rankin, A.B., and Vaughan, D.E. (1996). Identification of authentic estrogen receptor in cultured endothelial cells. Circulation 94, 727–733.10.1161/01.CIR.94.4.727Search in Google Scholar

Wade, C.B., Robinson, S., Shapiro, R.A., and Dorsa, D.M. (2001). Estrogen receptor (ER) α and ERβ exhibit unique pharmacologic properties when coupled to activation of the mitogen-activated protein kinase pathway. Endocrinology 142, 2336–2342.10.1210/endo.142.6.8071Search in Google Scholar

Wang, T.D., Wang, Y.H., Huang, T.S., Su, T.C., Pan, S.L., and Chen, S.Y. (2007). Circulating levels of markers of inflammation and endothelial activation are increased in men with chronic spinal cord injury. J. Formos. Med. Assoc. 106, 919–928.10.1016/S0929-6646(08)60062-5Search in Google Scholar

Weitzmann, M.N. and Pacifici R. (2006). Estrogen deficiency and bone loss: an inflammatory tale. J. Clin. Invest. 116, 1186–1194.10.1172/JCI28550Search in Google Scholar PubMed PubMed Central

Yaffe, K., Sawaya, G., Lieberburg, I., and Grady, D. (1998). Estrogen therapy in postmenopausal women. J. Am. Med. Assoc. 279, 688–695.10.1001/jama.279.9.688Search in Google Scholar PubMed

Yan, J., Li, B., Chen, J.W., Jiang, S.D., and Jiang, L.S. (2012). Spinal cord injury causes bone loss through peroxisome proliferator-activated receptor-γ and Wnt signalling. J. Cell Mol. Med. 16, 2968–2977.10.1111/j.1582-4934.2012.01624.xSearch in Google Scholar PubMed PubMed Central

Yune, T.Y., Kim, S.J., Lee, S.M., Lee, Y.K., Oh, Y.J., Kim, Y.C., Markelonis, G.J., and Oh, T.H. (2004). Systemic administration of 17β-estradiol reduces apoptotic cell death and improves functional recovery following traumatic spinal cord injury in rats. J. Neurotrauma 21, 293–306.10.1089/089771504322972086Search in Google Scholar PubMed

Yune, T.Y., Park, H.G., Lee, J.Y., and Oh, T.H. (2008). Estrogen-induced Bcl-2 expression after spinal cord injury is mediated through phosphoinositide-3-kinase/Akt-dependent CREB activation. J. Neurotrauma 25, 1121–1131.10.1089/neu.2008.0544Search in Google Scholar PubMed

Zandi, P.P., Carlson, M.C., Plassman, B.L., Welsh-Bohmer, K.A., Mayer, L.S., Steffens, D.C., and Breitner, J.C. (2002). Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County Study. J. Am. Med. Assoc. 288, 2123–2129.10.1001/jama.288.17.2123Search in Google Scholar PubMed

Zlotnik, A., Leibowitz, A., Gurevich, B., Ohayon, S., Boyko, M., Klein, M., Knyazer, B., Shapira, Y., and Teichberg, V.I. (2012). Effect of estrogens on blood glutamate levels in relation to neurological outcome after TBI in male rats. Intensive Care Med. 38, 137–144.10.1007/s00134-011-2401-3Search in Google Scholar PubMed

Received: 2015-7-22
Accepted: 2015-8-27
Published Online: 2015-10-13
Published in Print: 2016-4-1

©2016 by De Gruyter

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