Marc W. Halterman, M.D., Ph.D. , Associate Professor of Neurology, University of Rochester School of Medical and Dentistry, Center for Neurotherapeutics Discovery, will present seminar entitled: “Targeting immune-mediated cerebral reperfusion injury in the post cardiac arrest syndrome (PCAS)” on 11/3/17 from 11-12, LIB 110.
Systemic inflammation and multi-organ failure represent hallmarks of the Post Cardiac Arrest Syndrome (PCAS) that when present predict severe neurological injury and often fatal outcomes. Upon return of spontaneous circulation, ‘primed,’ neutrophils (PMNs) release degradative enzymes, cytokines, and reactive oxygen species that cause blood-brain-barrier dysfunction, neurovascular compromise, neuroinflammation, and tissue destruction. We have investigated a mouse model of PCAS that pairs transient global cerebral ischemia with exposure to the prototypical endotoxin lipopolysaccharide (LPS) that recapitulates major pathological hallmarks seen in PCAS. Analyses of the peripheral immune response have revealed that lung-brain coupling plays an important role in CNS ischemia-reperfusion injury. In this regard, we find that the inhibition of systemic PMN priming or the redox changes in the lung associated with ischemia-reperfusion injury convey potent neuroprotective effects in our model. Given the relationship between chronic lung disease and stroke, we propose that interventions that short-circuit lung-dependent immune priming will lead to improved neurological outcomes in patients presenting with a variety of cerebrovascular conditions.
ThursdayApril 25, 2024