Zena Vexler, PhD

Director of Research
Neurology
+1 415 502-7282

In humans and in rodents the stage of brain development at the time of stroke plays a key role in the pattern of brain damage. We are interested to understand the role of the immune system in neurovascular changes and injury in perinatal arterial stroke and childhood arterial stroke.

 

We were the first to establish and characterize the in vivo model of perinatal 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 made several discoveries of the mechanisms within immune-neurovascular axis that govern injury after perinatal stroke. Recently we established a model of childhood stroke and showed distinct patterns of blood-brain barrier permeability than after perinatal stroke. To critically approach the complexity of immune-vascular interactions, we use a broad arsenal of sophisticated experimental in vivo imaging tools, pharmacological tools and transgenic and reporter mouse lines to tease out the contribution of individual receptors and signaling molecules in microglial-neurovascular interaction in relation to stroke progression and outcomes.

Publications: 

Scavenger receptor CD36 governs recruitment of myeloid cells to the blood-CSF barrier after stroke in neonatal mice.

Journal of neuroinflammation

Rayasam A, Mottahedin A, Faustino J, Mallard C, Vexler ZS

Maternal n-3 Polyunsaturated Fatty Acid Enriched Diet Commands Fatty Acid Composition in Postnatal Brain and Protects from Neonatal Arterial Focal Stroke.

Translational stroke research

Chumak T, Lecuyer MJ, Nilsson AK, Faustino J, Ardalan M, Svedin P, Sjöbom U, Ek J, Obenaus A, Vexler ZS, Mallard C

Viral mimetic triggers cerebral arteriopathy in juvenile brain via neutrophil elastase and NETosis.

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

Rayasam A, Jullienne A, Chumak T, Faustino J, Szu J, Hamer M, Ek CJ, Mallard C, Obenaus A, Vexler ZS

Mesenchymal Stem Cell (MSC)-Derived Extracellular Vesicles Protect from Neonatal Stroke by Interacting with Microglial Cells.

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics

Pathipati P, Lecuyer M, Faustino J, Strivelli J, Phinney DG, Vexler ZS

Neonatal stroke enhances interaction of microglia-derived extracellular vesicles with microglial cells.

Neurobiology of disease

Lecuyer M, Pathipati P, Faustino J, Vexler ZS

Microglia-Leukocyte Axis in Cerebral Ischemia and Inflammation in the Developing Brain.

Acta physiologica (Oxford, England)

Rayasam A, Fukuzaki Y, Vexler ZS

Neonatal stroke and TLR1/2 ligand recruit myeloid cells through the choroid plexus in a CX3CR1-CCR2 and context specific manner.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Rayasam A, Faustino J, Lecuyer M, Vexler ZS

Sex-Dependent Effects of Perinatal Inflammation on the Brain: Implication for Neuro-Psychiatric Disorders.

International journal of molecular sciences

Ardalan M, Chumak T, Vexler Z, Mallard C

CX3CR1-CCR2-dependent monocyte-microglial signaling modulates neurovascular leakage and acute injury in a mouse model of childhood stroke.

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

Faustino J, Chip S, Derugin N, Jullienne A, Hamer M, Haddad E, Butovsky O, Obenaus A, Vexler ZS

Positive and negative conditioning in the neonatal brain.

Conditioning medicine

Vexler ZS, Mallard C, Hagberg H

A Novel Technique for Visualizing and Analyzing the Cerebral Vasculature in Rodents.

Translational stroke research

Salehi A, Jullienne A, Wendel KM, Hamer M, Tang J, Zhang JH, Pearce WJ, DeFazio RA, Vexler ZS, Obenaus A

Microglia and Neonatal Brain Injury.

Neuroscience

Mallard C, Tremblay ME, Vexler ZS

Live imaging of the innate immune response in neonates reveals differential TLR2 dependent activation patterns in sterile inflammation and infection.

Brain, behavior, and immunity

Lalancette-Hébert M, Faustino J, Thammisetty SS, Chip S, Vexler ZS, Kriz J

Effects of therapeutic hypothermia on white matter injury from murine neonatal hypoxia-ischemia.

Pediatric research

Koo E, Sheldon RA, Lee BS, Vexler ZS, Ferriero DM

"Small Blood Vessels: Big Health Problems?": Scientific Recommendations of the National Institutes of Health Workshop.

Journal of the American Heart Association

Bosetti F, Galis ZS, Bynoe MS, Charette M, Cipolla MJ, Del Zoppo GJ, Gould D, Hatsukami TS, Jones TL, Koenig JI, Lutty GA, Maric-Bilkan C, Stevens T, Tolunay HE, Koroshetz W

Mesenchymal stem cells attenuate MRI-identifiable injury, protect white matter, and improve long-term functional outcomes after neonatal focal stroke in rats.

Journal of neuroscience research

van Velthoven CT, Dzietko M, Wendland MF, Derugin N, Faustino J, Heijnen CJ, Ferriero DM, Vexler ZS

Microglial Cells Prevent Hemorrhage in Neonatal Focal Arterial Stroke.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Fernández-López D, Faustino J, Klibanov AL, Derugin N, Blanchard E, Simon F, Leib SL, Vexler ZS

Lack of the scavenger receptor CD36 alters microglial phenotypes after neonatal stroke.

Journal of neurochemistry

Li F, Faustino J, Woo MS, Derugin N, Vexler ZS

LSR/angulin-1 is a tricellular tight junction protein involved in blood-brain barrier formation.

The Journal of cell biology

Sohet F, Lin C, Munji RN, Lee SY, Ruderisch N, Soung A, Arnold TD, Derugin N, Vexler ZS, Yen FT, Daneman R

The role of inflammation in perinatal brain injury.

Nature reviews. Neurology

Hagberg H, Mallard C, Ferriero DM, Vannucci SJ, Levison SW, Vexler ZS, Gressens P

Pathophysiology and neuroprotection of global and focal perinatal brain injury: lessons from animal models.

Pediatric neurology

Titomanlio L, Fernández-López D, Manganozzi L, Moretti R, Vexler ZS, Gressens P

Barrier mechanisms in neonatal stroke.

Frontiers in neuroscience

Kratzer I, Chip S, Vexler ZS

Stem cells for neonatal stroke- the future is here.

Frontiers in cellular neuroscience

van Velthoven CT, Gonzalez F, Vexler ZS, Ferriero DM

Mechanisms of perinatal arterial ischemic stroke.

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

Fernández-López D, Natarajan N, Ashwal S, Vexler ZS

Acute and chronic vascular responses to experimental focal arterial stroke in the neonate rat.

Translational stroke research

Fernández-López D, Faustino J, Derugin N, Vexler ZS

Delayed VEGF treatment enhances angiogenesis and recovery after neonatal focal rodent stroke.

Translational stroke research

Dzietko M, Derugin N, Wendland MF, Vexler ZS, Ferriero DM

Mesenchymal stem cell transplantation attenuates brain injury after neonatal stroke.

Stroke

van Velthoven CT, Sheldon RA, Kavelaars A, Derugin N, Vexler ZS, Willemen HL, Maas M, Heijnen CJ, Ferriero DM

Genetic deletion of CD36 enhances injury after acute neonatal stroke.

Annals of neurology

Woo MS, Wang X, Faustino JV, Derugin N, Wendland MF, Zhou P, Iadecola C, Vexler ZS

Blood-brain barrier permeability is increased after acute adult stroke but not neonatal stroke in the rat.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Fernández-López D, Faustino J, Daneman R, Zhou L, Lee SY, Derugin N, Wendland MF, Vexler ZS

Reduced infarct size and accumulation of microglia in rats treated with WIN 55,212-2 after neonatal stroke.

Neuroscience

Fernández-López D, Faustino J, Derugin N, Wendland M, Lizasoain I, Moro MA, Vexler ZS

Microglial cells contribute to endogenous brain defenses after acute neonatal focal stroke.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Faustino JV, Wang X, Johnson CE, Klibanov A, Derugin N, Wendland MF, Vexler ZS

Cerebrovascular disease in children: recent advances in diagnosis and management.

Journal of child neurology

Bowers KJ, Deveber GA, Ferriero DM, Roach ES, Vexler ZS, Maria BL

Magnetic resonance imaging (MRI) as a translational tool for the study of neonatal stroke.

Journal of child neurology

Dzietko M, Wendland M, Derugin N, Ferriero DM, Vexler ZS

Cerebellar abnormalities following hypoxia alone compared to hypoxic-ischemic forebrain injury in the developing rat brain.

Neurobiology of disease

Biran V, Heine VM, Verney C, Sheldon RA, Spadafora R, Vexler ZS, Rowitch DH, Ferriero DM

Role of vasodilator stimulated phosphoprotein in VEGF induced blood-brain barrier permeability in endothelial cell monolayers.

International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience

Davis B, Tang J, Zhang L, Mu D, Jiang X, Biran V, Vexler Z, Ferriero DM

Erythropoietin enhances long-term neuroprotection and neurogenesis in neonatal stroke.

Developmental neuroscience

Gonzalez FF, McQuillen P, Mu D, Chang Y, Wendland M, Vexler Z, Ferriero DM

Macrophages are comprised of resident brain microglia not infiltrating peripheral monocytes acutely after neonatal stroke.

Journal of neurochemistry

Denker SP, Ji S, Dingman A, Lee SY, Derugin N, Wendland MF, Vexler ZS

Inflammation in adult and neonatal stroke.

Clinical neuroscience research

Vexler ZS, Tang XN, Yenari MA

Translational stroke research in the developing brain.

Pediatric neurology

Vexler ZS, Sharp FR, Feuerstein GZ, Ashwal S, Thoresen M, Yager JY, Ferriero DM

Minocycline confers early but transient protection in the immature brain following focal cerebral ischemia-reperfusion.

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

Fox C, Dingman A, Derugin N, Wendland MF, Manabat C, Ji S, Ferriero DM, Vexler ZS

Antiapoptotic and anti-inflammatory mechanisms of heat-shock protein protection.

Annals of the New York Academy of Sciences

Yenari MA, Liu J, Zheng Z, Vexler ZS, Lee JE, Giffard RG

Hsp70 overexpression sequesters AIF and reduces neonatal hypoxic/ischemic brain injury.

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

Matsumori Y, Hong SM, Aoyama K, Fan Y, Kayama T, Sheldon RA, Vexler ZS, Ferriero DM, Weinstein PR, Liu J

Erythropoietin improves functional and histological outcome in neonatal stroke.

Pediatric research

Chang YS, Mu D, Wendland M, Sheldon RA, Vexler ZS, McQuillen PS, Ferriero DM

Differential vulnerability of immature murine neurons to oxygen-glucose deprivation.

Experimental neurology

Jiang X, Mu D, Manabat C, Koshy AA, Christen S, Täuber MG, Vexler ZS, Ferriero DM

Manipulation of antioxidant pathways in neonatal murine brain.

Pediatric research

Sheldon RA, Jiang X, Francisco C, Christen S, Vexler ZS, Täuber MG, Ferriero DM

Regulation of hypoxia-inducible factor 1alpha and induction of vascular endothelial growth factor in a rat neonatal stroke model.

Neurobiology of disease

Mu D, Jiang X, Sheldon RA, Fox CK, Hamrick SE, Vexler ZS, Ferriero DM

Fructose-1,6-bisphosphate preserves intracellular glutathione and protects cortical neurons against oxidative stress.

Brain research

Vexler ZS, Wong A, Francisco C, Manabat C, Christen S, Täuber M, Ferriero DM, Gregory G

Reperfusion differentially induces caspase-3 activation in ischemic core and penumbra after stroke in immature brain.

Stroke

Manabat C, Han BH, Wendland M, Derugin N, Fox CK, Choi J, Holtzman DM, Ferriero DM, Vexler ZS

Rat forebrain neurogenesis and striatal neuron replacement after focal stroke.

Annals of neurology

Parent JM, Vexler ZS, Gong C, Derugin N, Ferriero DM

Molecular and biochemical mechanisms of perinatal brain injury.

Seminars in neonatology : SN

Vexler ZS, Ferriero DM

Evolution of brain injury after transient middle cerebral artery occlusion in neonatal rats.

Stroke

Derugin N, Wendland M, Muramatsu K, Roberts TP, Gregory G, Ferriero DM, Vexler ZS

Toxicity of fructose-1,6-bisphosphate in developing normoxic rats.

Pharmacology & toxicology

Vexler Z, Berrios M, Ursell PC, Sola A, Ferriero DM, Gregory GA

Neonatal reversible focal cerebral ischemia: a new model.

Neuroscience research

Derugin N, Ferriero DM, Vexler ZS

Transient cerebral ischemia. Association of apoptosis induction with hypoperfusion.

The Journal of clinical investigation

Vexler ZS, Roberts TP, Bollen AW, Derugin N, Arieff AI

Activation of Na+-H+ exchange is necessary for RhoA-induced stress fiber formation.

The Journal of biological chemistry

Vexler ZS, Symons M, Barber DL

Sensitivity of high-speed "perfusion-sensitive" magnetic resonance imaging to mild cerebral ischemia.

European radiology

Roberts TP, Vexler ZS, Vexler V, Derugin N, Kucharczyk J

Evaluation of recombinant human basic fibroblast growth factor (rhbFGF) as a cerebroprotective agent using high speed MR imaging.

Brain research

Roberts TP, Vexler ZS, Derugin N, Kozniewska E, Kucharczyk J, Emmett CJ

Age, gender, and vasopressin affect survival and brain adaptation in rats with metabolic encephalopathy.

The American journal of physiology

Arieff AI, Kozniewska E, Roberts TP, Vexler ZS, Ayus JC, Kucharczyk J

Hormonal dependence of the effects of metabolic encephalopathy on cerebral perfusion and oxygen utilization in the rat.

Circulation research

Kozniewska E, Roberts TP, Vexler ZS, Oseka M, Kucharczyk J, Arieff AI

Hypoxic and ischemic hypoxia exacerbate brain injury associated with metabolic encephalopathy in laboratory animals.

The Journal of clinical investigation

Vexler ZS, Ayus JC, Roberts TP, Fraser CL, Kucharczyk J, Arieff AI

Mechanisms of brain injury associated with partial and complete occlusion of the MCA in cat.

Acta neurochirurgica. Supplementum

Vexler ZS, Roberts TP, Derugin N, Kozniewska E, Arieff AI, Kucharczyk J

Severe brain edema associated with cumulative effects of hyponatremic encephalopathy and ischemic hypoxia.

Acta neurochirurgica. Supplementum

Vexler ZS, Roberts TP, Kucharczyk J, Arieff AI

High-speed MR imaging of ischemic brain injury following stenosis of the middle cerebral artery.

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

Roberts TP, Vexler Z, Derugin N, Moseley ME, Kucharczyk J

Echo-planar perfusion-sensitive MR imaging of acute cerebral ischemia.

Radiology

Kucharczyk J, Vexler ZS, Roberts TP, Asgari HS, Mintorovitch J, Derugin N, Watson AD, Moseley ME

Rapid MR imaging of a vascular challenge to focal ischemia in cat brain.

Journal of magnetic resonance imaging : JMRI

de Crespigny AJ, Wendland MF, Derugin N, Vexler ZS, Moseley ME

Cerebrovascular transit characteristics of DyDTPA-BMA and GdDTPA-BMA on normal and ischemic cat brain.

AJNR. American journal of neuroradiology

Kucharczyk J, Asgari H, Mintorovitch J, Vexler Z, Rocklage S, Watson A, Moseley M

Comparison of Gd- and Dy-chelates for T2 contrast-enhanced imaging.

Magnetic resonance in medicine

Moseley ME, Vexler Z, Asgari HS, Mintorovitch J, Derugin N, Rocklage S, Kucharczyk J

Magnetic resonance imaging of brain perfusion using the nonionic contrast agents Dy-DTPA-BMA and Gd-DTPA-BMA.

Investigative radiology

Kucharczyk J, Asgari H, Mintorovitch J, Vexler Z, Moseley M, Watson A, Rocklage S