Michael L. James, MD
Duke University Hospital
FAER Mentored Research Training Grant: “Pharmacogenomic Influence of ApoE and Mimetic Peptide on Neurologic Outcomes as a Paradigm for Targeted Therapeutic Development in a Murine Model of Intracerebral Hemmorrhage”
Mentors: Daniel T. Laskowitz, MD; David S. Warner, MD

Summary: As a frequent admitting diagnosis to neurosurgical intensive care units, intracerebral hemorrhage (ICH) is vastly understudied but known to generate marked neuroinflammatory response with poor clinical outcome. The aim is to develop rational, targeted pharmacogenomic therapies by using a murine model of ICH in transgenic systems. By setting up a series of experiments utilizing mice expressing human apolipoproteinE isoforms (apoE3 and apoE4), the isoform-specific effects on neuroinflammation after ICH can be identified. Thus, testing the specific hypothesis that endogenous expression of apoE modifies neurological deficits by modulating glial activation in an isoform-specific manner will allow for the development of rationally-derived mimetic peptides to manipulate these effects. By examining cytokine generation with complementary histochemical techniques, determination of the extent to which apoE and mimetic peptides confer neuroprotection through neuroinflammatory modulation will be made, demonstrating apoE as a compelling target for pharmacogenomic therapy to improve recovery for critically ill patients with ICH.

Jennifer K. Lee, MD
Johns Hopkins University
FAER Research Fellowship Grant: “Cerebrovascular Autoregulation after Pediatric Cardiac Arrest”
Mentor: Raymond C. Koehler, PhD

Summary: Pediatric cardiac arrest often results in permanent neurologic injury despite efforts to protect the brain by inducing hypothermia after resuscitation. Cerebrovascular autoregulation maintains constant blood flow to the brain across changes in blood pressure. Deranged autoregulation and inappropriate blood pressure management may contribute to poor neurologic outcomes. Autoregulation has not been adequately studied after resuscitation from cardiac arrest in children, and the effects of hypothermia are unclear. We hypothesize that autoregulation is impaired and that different temperatures affect autoregulation after resuscitation from cardiac arrest. In neonatal swine resuscitated from arrest, cerebral blood flow and autoregulatory indices will be monitored during normothermia and hypothermia. Blood pressure will be raised or lowered to test autoregulatory function and the limits of autoregulation. Blood pressure management that supports autoregulation is integral to improving neurologic outcomes after cardiac arrest. Data derived from these experiments will provide critical evidence for improving clinical guidelines in pediatric resuscitation.