Publication Date

2012

Document Type

Thesis

Committee Members

James Olson (Advisor), Robert Putnum (Committee Member), Christopher Wyatt (Committee Member)

Degree Name

Master of Science (MS)

Abstract

Oxidative stress is an important result of cerebral ischemia and has been directly linked to hippocampal swelling and cytotoxic brain edema in vitro. Swollen brain cells activate volume regulatory mechanisms including a significant efflux of the endogenous sulfonic amino acid taurine via volume-regulated anion channels (VRACs). Studies in brain slice preparations also suggest that the excitatory amino acid glutamate plays an important role in both brain tissue swelling and in cell volume regulation. We examined relationships between oxidative stress, glutamate receptor activation, cell swelling, and volume regulation in acutely prepared slices of rat hippocampus. Our results indicate that the release of taurine from intracellular stores is critical for isoosmotic volume regulation of the hippocampus exposed to oxidative stress. Further, taurine is lost from hippocampal cells during oxidative stress via the volume activated anion channel (VRAC). The glutamate AMPA receptors, and to a lesser extent NMDA receptors are coupled to hippocampal swelling during oxidative stress. Our results further suggest volume regulation of the hippocampus is regulated, in part, by glutamate signalling via NMDA and AMPA receptors. Establishing the importance of taurine mobilization during swelling induced by oxidative stress and presenting a significant role for glutamate receptors in swelling and volume regulation is an important step in understanding the cellular response to cytotoxic brain edema. Future work is needed to further our understanding of the response and adaptation of brain cells to edema leading to improved treatments and recovery from these devastating pathological conditions.

Page Count

156

Department or Program

Department of Neuroscience, Cell Biology & Physiology

Year Degree Awarded

2012


Included in

Anatomy Commons

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