Molecular and Behavioral Mechanisms of Cerebral Ischemia

Babcock, Alex

Abstract

Ischemic injury to the brain can occur following cardiac arrest or cardiopulmonary bypass surgery. Regions of the hippocampus, a structure implicated in learning and memory, are extremely vulnerable to cerebral ischemia. This vulnerability appears to be related to inherent biochemical differences of these hippocampal neurons. The enzyme calcium/calmodulin kinase II (CaM kinase II), activated by a pronounced influx of Ca2+ during ischemia, has been implicated. The first specific aim of this proposal will be to determine regional changes in hippocampal CaM kinase II mRNA following ischemic insults. To accomplish this aim, CaM kinase II expression in vulnerable and non-vulnerable areas of the hippocampus will be compared using an in situ hybridization technique. These studies will utilize a gerbil ischemia model and behavioral markers of hippocampal cell death. A second specific aim of this proposal will be to establish the effects of hypothermia on ischemic-induced regional alterations of CaM kinase II expression. Hypothermia protects the hippocampus during an ischemic episode. We plan to induce hypothermia prior to ischemic insults with neurotensin, a peptide previously shown to be neuroprotective. Using in situ hybridization techniques, we will determine if neurotensin-induced hypothermia attenuates ischemic-related alterations project and encourage to contribute to the ongoing development of my research program. Specific responsibilities will include behavioral data collection, assisting with surgical procedures, and evaluation of histological damage to the hippocampus. These various activities will be occurring almost daily including some weekends. The MBRS students will attend weekly laboratory meetings and will be required to present and critic current research articles relevant to the ongoing project. The MBRS student would be working approximately 15 hr./week in my laboratory. The student will be required to learn spreadsheet (Microsoft Excel) and graphing program (Grapher for Windows) within the first 2 months. These skills will be used by the student to interpret and summarize collected data. The MBRS student will gain an appreciation for all aspects of the research process including data collection, analysis/presentation of results, and manuscript preparation.