Dr. Sylvain Doré
Battling Neurodegenerative Disorders: Stroke, TBI, Alzheimer’s and Aging
Professor of Anesthesiology, Neurology, Psychiatry, Psychology, Pharmaceutics,and Neuroscience;
Director of Research Programs, Department of Anesthesiology;
Investigator, McKnight Brain Institute and CTRND
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
Research Focus and Aims
The goal of the team effort directed by Sylvain is to discover new effective mechanisms that limit neuronal dysfunction associated with ischemic and hemorrhagic Stroke (IS, ICH, SAH), traumatic brain injury (TBI), Alzheimer disease (AD), aging, and various other neurological disorders. TThe overall objective 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. This work is supported in part by NIH/NINDS
- We also intend to understand of the protective role of the heme metabolites in the brain using cellular/molecular techniques and various models of ischemic and hemorrhagic stroke, AD, 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.
- One objective is focused on understanding the actions of prostaglandin (PG) generated by the degradation of arachidonic acid by cyclooxygenase enzymes. These enzymes are the rate-limiting steps for the production of PGs, which are key elements in the inflammatory response. The resulting consequences are suggested to play an important role in the loss of normal neuronal functions associated with aging and neurodegenerative disorders. This work is supported in part by NIH/NINDS
- Our lab also provides molecular evidence for the potential therapeutic applications of complementary and alternative medicines. Using cultures of neurons it was observed that treatment with a standardized extracts of Korean Ginseng or of Ginkgo biloba could alter the presence of specific genes/proteins important in neuronal function. The lab is exploring the regulation of the transcriptional factor Nrf2, and the increased expression of phase 2 protective enzymes, notably heme oxygenase. Also results have been obtained using resveratrol and other polyphenols, which appear to be active ingredients concentrated in red wines, and which has been proposed to explain some of the beneficial effects associated with the so called “French Paradox.” Similarly, experiments have provided evidence for a unique protective mechanism for the flavanol epicatechin which can be enriched in dark chocolate. These bioactive nutrients could provide resistance against damage induced by free radicals, the toxins which are generated with aging and are the hallmark of many neurodegenerative processes. This work is supported in part by NIH/NCCIH/ODS
Volunteers are being accepted for conducting research in Dr. Sylvain Doré’s lab. The team focuses on investigating novel treatments of neurological disorders. Specifically, current projects involve the utilization of various preclinical models to uncover the neurobiological processes of ischemic and hemorrhagic strokes, and those associated with Aging and vascular cognitive impairments. The lab is interested in inflammation, antioxidants and natural products. Volunteers will have the opportunity to learn about the rigorous process of scientific inquiry and gain hands-on experience conducting experiments (for example, PCR-genotyping, perfusion, brain harvesting, slicing, staining, and quantification/analysis, etc.). Those interested will be asked to commit an average of 3 X 5h-block/week; additionally, summer “internship” is encouraged. Please email us if you are interested in volunteering or would like more information about this exciting opportunity.
- 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.
- Leclerc JL, Garcia JM, Diller MA, Carpenter A-M, Kamat PK, Hoh B, Doré S. A comparison of pathophysiology in humans and rodent models of subarachnoid hemorrhage. Front Molec Neurosci. 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.