The pathology which results from traumatic brain injury (TBI) have long been believed to be immediate and irreversible. However, recently it has been shown that, although the primary effects are virtually unavoidable, the secondary effects manifest themselves through biochemical processes set in motion at the time of the injury. These events are frequently mediated through the process of excitotoxicity, which results from a widespread release of excitatory neurotransmitters. These neurotransmitters go on to activate both ionotropic and metabotropic receptors. The signal transduction initiated through these receptor populations gives rise to changes in gene expression.
One result of this release of neurotransmitter is an influx of calcium by means of excitatory receptors on the cell. The neurotransmitters upon which most research is focused are glutamate, aspartate, and acetylcholine. Current research is aimed at investigating antagonists to this process as well as elucidating steps within the process. Antagonists primarily function to reduce the calcium toxicity through modulation of receptor activity. However, the therapeutic window for effective antagonist usage is short. Therefore, although they may represent a viable treatment option, they need to be administered as early as possible following the injury to have the greatest effect.
The purpose of this paper is to provide a summary of the available literature on TBI and excitotoxicity with a focus on changes in gene regulation. This paper will summarize information on the steps inVolved in the intracellular signaling cascade following brain injury and provide insight to further sites for regulation and treatment. This will also allow for development hypotheses on the possible roles of some of the genes whose expression is already known to be altered.
| Identifer | oai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd-6164 |
| Date | 01 January 1998 |
| Creators | Malhotra, Rajiv |
| Publisher | VCU Scholars Compass |
| Source Sets | Virginia Commonwealth University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | © The Author |
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