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Séminaire - Zena Vexler"Microglial-neurovascular axis in stroke: role of brain immaturity".

Abstract :

 Perinatal arterial ischemic stroke is as common in term human babies as it is in the elderly, but many underlying stroke mechanisms are distinct. I will discuss how maturation of microglial cells and of blood-brain barrier constituents affect functional integrity of the barrier and injury after experimental perinatal and adult arterial focal stroke.

Selected publications

Li F, Faustino J, Woo M, Derugin N, Vexler ZS. Lack of the scavenger
receptor cd36 alters microglial phenotypes after neonatal stroke. J
Neurochem. 2015;Jul 30. doi: 10.1111/jnc.13239. PMID: 26223273

Mallard C and Vexler ZS. “Modeling Ischemia in the Immature Brain: How
Translational Are Animal Models?” Stroke, 2015. 46:3006-11. doi:
10.1161/STROKEAHA.115.007776. Epub 2015 Aug 13. PMID: 26272384

Hagberg H, Mallard C, Ferriero DM, Vannucci S, Levison S, Vexler ZS and
Gressens P. “Role of inflammation in perinatal brain injury”. Nature
Review Neurology 2015, Apr;11(4):192-208. doi: 10.1038/nrneurol.2015.13.
Epub 2015 Feb 17. Review. PMID: 25686754. PMC Journal - In process.

SohetF, LinC, MunjiR, LeeS, RuderischN, SoungA, ArnoldT, DeruginN,
Vexler ZS, YenF and Daneman R “LSR/Angulin-1 is a tricellular tight
junction protein involved in blood-brain barrier formation” J Cell Biol.
Mar 16;208(6):703-11. doi: 10.1083/jcb.201410131. Epub 2015 Mar 9. PMID:
25753034. PMCID: PMC4362448

Fernández-López D, Natarajan N, Ashwal S, and Vexler ZS. “Mechanisms of
Perinatal Arterial Ischemic Stroke”, JCBFM, 2014, 34(6):921-923. PMID:
24667913

van Velthoven CT, Sheldon RA, Kavelaars A, Derugin N, Vexler ZS,
Willemen HL, Maas M, Heijnen CJ, Ferriero DM. “Mesenchymal stem cell
transplantation attenuates brain injury after neonatal stroke”. Stroke.
2013, 44(5):1426-32. PMID: 23539530

Fernández-López D, FaustinoJ, DeruginN, VexlerZS. “Acute and chronic
vascular responses to experimental focal arterial stroke in the neonate
rat”. Translational Stroke Res, 2013, 4 (2):179-188. PMCID: PMC3665524

Scientific focus :

Zinaida S. Vexler, Ph.D.
Professor in Neurology
University California San Francisco
At UCSF I have served as the Director of Research, Neonatal Brain Disorders Center, since 2003. I have served on study sections at the NIH and chaired Brain 2 and Brain 3 Committees, the AHA. I have multi-disciplinary training in chemistry, biochemistry, pharmacology, and physiology and extensive expertise in stroke models.

For more than twenty years my research has been centered on the mechanisms of experimental stroke. I have contributed to the fields of cerebrovascular and cellular injury after experimental stroke first in the adult and, over more than fifteen years, in the neonate. I investigated relationships between severity of perfusion deficits and disturbances in brain homeostasis, ischemia-induced cell death, identification of intracellular mechanisms of post-ischemic neuronal death, and preclinical testing of several classes of pharmacologic agents, including small molecules, growth factors and mesenchymal stem cells.

My lab was the first to establish model of neonatal focal stroke in rats and ours is the only laboratory that can produce focal arterial stroke in neonatal mice. With these age appropriate models, we discovered that blood-brain barrier function is strikingly more preserved after acute stroke in neonates than in adults. We also discovered that microglia serve as endogenous neuroprotectants in neonatal stroke.