Excitotoxicity in Traumatic Brain Injury
Date of Award
2007
Document Type
Thesis
Degree Name
Bachelors
Department
Natural Sciences
First Advisor
Walstrom, Katherine
Keywords
Brain, Trauma, Excitotoxicity, Mitochondrial Permeability Transition Injury, Medical Calcium, Ca2+, NMDAR, AMPA, NMDA, Kainate Channel
Area of Concentration
Natural Sciences
Abstract
Traumatic brain injury (TBI) is a common and devastating condition. Excitotoxicity, one of the most harmful aspects of cellular injury that occurs as a result of TBI, is a biological cascade of events that frequently culminates in neuronal death. A crucial factor in excitotoxicity is entry of calcium (Ca2+) into neurons. However, Ca2+ that enters through N-methyl- D-aspartate receptors (NMDARs) is more harmful than Ca2+ entering through other channels. This finding gave rise to the source specificity hypothesis, the idea that calcium entry through some receptors may be physically coupled to damaging processes Another key feature of excitotoxic cell death is Ca2+ uptake by mitochondria, an excess of which leads to the deadly mitochondrial permeability transition (MPT). MPT in neuronal mitochondria may be the cause of delayed Ca2+ deregulation (DCD), a secondary spike in intracellular Ca2+ load that is invariably followed by cell death. Since NMDARs are the primary contributor to excitotoxic cell death, NMDAR antagonists have held much promise as a TBI treatment, and have been successful in animal trials. However, clinical trials using NMDAR antagonist drugs for TBI have uniformly failed to show benefit, possibly due to differences in animal and clinical trial design or to the inherent unsuitability of the drugs or of animal models for human TBI. However, lessons learned from these trials can be applied to new antiexcitotoxic therapies, such as drugs that only partially block NMDARs, or that downmodulate their function. These new treatments could prevent death and disability for countless people.
Recommended Citation
MacLean, Dell, "Excitotoxicity in Traumatic Brain Injury" (2007). Theses & ETDs. 3823.
https://digitalcommons.ncf.edu/theses_etds/3823
Rights
This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.