Battling Neurodegenerative Disorders: Stroke, TBI, Alzheimer’s and Aging
The goal of the laboratory of Dr. Sylvain Doré is to discover new mechanisms that limit neuronal dysfunction associated with stroke (e.g. IS, ICH, SAH), traumatic brain injury (TBI), Alzheimer disease (AD), aging and other neurological disorders.
The overall goal is to slow down the progression of the disease, and ultimately stop it. To do so, the aim is to limit cell death resulting from either acute and/or chronic neurodegenerative conditions, re-establish normal cerebral blood flow, limit inflammation, and restore regular cellular functions. Using a variety of in vitro and in vivo protocols, using preclinical and human specimens, several new hypotheses and potential therapies are being investigated and developed.
One objective is focused on understanding the unique properties of hemoglobin, heme and iron in the brain using cellular/molecular techniques and various models of stroke, traumatic brain injury/concussion, Alzheimer disease and aging.
New knowledge is gained specifically, by investigating the action and the role of activity of the heme oxygenase enzyme and its unique bioactive metabolites, namely, carbon monoxide, iron, biliverdin, and bilirubin.
Thirdly our lab provides molecular evidence for the potential therapeutic applications of complementary and alternative medicines (CAM).
Using cultures of neurons and brain tissues, Dr. Doré has observed that pre-treatment with a standardized extract of Ginkgo biloba or Ginseng could alter the presence of specific genes/proteins important in neuronal function. Individual components of the extract are ineffective, supporting the synergistic principals of Chinese medicine. Similar experiments and results have been obtained using resveratrol, which appears to be an active ingredient concentrated in red wines, and which has been proposed to explain some of the beneficial effects associated with the so called “French Paradox.” These alternative medicines could provide resistance against damage induced by free radicals, the toxins that are generated with aging and are the hallmark of many neurodegenerative processes.
Ultimately, the aim is to perform basic research using innovative tools to test original hypotheses and find new treatments that could have clinical applications for the population.
Sylvain Doré, PhD, FAHA
Professor of Anesthesiology, Neurology, Psychiatry, Psychology, Pharmaceutics and Neuroscience;
Director of Research Programs, Department of Anesthesiology;
Investigator, Center for Translational Research in Neurodegenerative Disease (CTRND)
Investigator, McKnight Brain Institute (MBI)
Member, Faculty Senate Steering Committee
Vice-Chair, Research and Scholarship Council
Post Doc, Neuroscience (Sol Snyder), Johns Hopkins University, 1999
Post Doc, Psychiatry (Remi Quirion), McGill University, 1996
PhD, Biomedical Sciences, University of Montreal, 1994
MS, Pharmacology, University of Quebec, 1990
BS, Biochemistry, University of Quebec, 1988
Contact Dr. Doré
- Bulters D, Gaastra B, Zolnourian A, Alexander S, Ren D, Blackburn S, Borsody M, Doré S, Galea J, Iihara K, Nyquist P, Galea I. Haemoglobin scavenging in the brain: biology and clinical implications. Nature Rev. Neurol. In Press, 2018
- Hourani S, Motwani K, Wajima D, Fazal H, Jones CH, Doré S, Hosaka K, Hoh BL. Local delivery is critical for MCP-1 mediated site-specific murine aneurysm healing. Front Neurol. In Press, 2018.
- Liu L, Vollmer MK, Fernandez V, Dweik Y, Weider M, Doré S. Korean Red Ginseng pretreatment protects against long-term sensorimotor defitcits after ischemic stroke likely through Nrf2. Front. Cell Neurosci, In Press, 2018.
- Chen G, Thakkar M, Robinson C, Doré S. Limb remote ischemic conditioning: Mechanisms, anesthetics, and the potential for expanding therapeutic options. Front Neurol, In Press, 2018.
- Leclerc JL, Lampert AS, Loyola CA, Schlakman B, Vasilopolous T, Svendsen P, Moestrup SK, Doré S. The absence of the CD163 receptor has distinct temporal influences on intracerebral hemorrhage outcomes. J Cereb Blood Flow & Metab. 38(2):262-273, 2018.
- Garcia JM, Stillings SA, Leclerc JL, Edwards NJ, Robicsek SA, Hoh BL, Blackburn S, Doré S. Role of interleukin-10 in acute brain injuries. Front. Neurol. 8:244, 2017.
- Leclerc JL, Santiago-Moreno J, Dang A, Lampert AS, Cruz PE, Rosario AM, Golde TE, Doré S. Increased brain hemopexin levels improve outcomes after intracerebral hemorrhage. J Cereb Blood Flow & Metab. doi: 10.1177/0271678X16679170. 2016.
- Ma B, Day J, Tolosano E, Doré S. Deletion of the hemopexin or heme oxygenase-2 gene aggravates brain injury following stroma-free hemoglobin-induced intracerebral hemorrhage. J. Neuroinflam. 12:26, 2016
- Leclerc J, Lampert AS, Diller MA, Doré S. PGE2-EP3 signaling exacerbates intracerebral hemorrhage outcomes in 24-mo-old mice. Am J Physiol 310:H1725-34, 2016.
- Glushakov AV, Arias RA, Tolosano E, Doré S. Age-dependent effects of haptoglobin deletion in neurobehavioral and anatomical outcomes following TBI. Front. Mol. Biosci., 3:24, 2016.
- Leclerc JL, Blackburn S, Neal D, Mendez NV, Wharton JA, Waters MF, Doré S. Haptoglobin phenotype predicts the development of focal and global cerebral vasospasm and may influence outcomes after aneurysmal subarachnoid hemorrhage. Proc Natl Acad Sci 112:1155-60, 2015.