title: Apoptosis after traumatic brain injury.
abstract: Apoptosis of neurons and glia contribute to the overall pathology of traumatic brain injury (TBI) in both humans and animals. In both head-injured humans and following experimental brain injury, apoptotic cells have been observed alongside degenerating cells exhibiting classic necrotic morphology. Neurons undergoing apoptosis have been identified within contusions in the acute port-traumatic period, and in regions remote from the site of impact in the days and weeks after trauma. Apoptotic oligodendrocytes and astrocytes have been observed within injured white matter tracts. We review the regional and temporal patterns of apoptosis following TBI and the possible mechanisms underlying trauma-induced apoptosis. While excitatory amino acids, increases in intracellular calcium, and free radicals can all cause cells to undergo apoptosis, in vitro studies have determined that neural cells can undergo apoptosis via many other pathways. It is generally accepted that a shift in the balance between pro- and anti-apoptotic protein factors towards the expression of proteins that promote death may be one mechanism underlying apoptotic cell death. The effect of TBI on regional cellular patterns of expression of survival promoting-proteins such as Bcl-2, Bcl-xL, and extracellular signal regulated kinases, and death-inducing proteins such as Bax, c-Jun N-terminal kinase, tumor-suppressor gene, p53, and the caspase family of proteases are reviewed. Finally, in light of pharmacologic strategies that have been devised to reduce the extent of apoptotic cell death in animal models of TBI, our review also considers whether apoptosis may serve a protective role in the injured brain.
authors.affiliation: Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia 19104, USA. rramesh@mail.med.upenn.edu
authors.forename: R
authors.initials: R
authors.lastname: Raghupathi
authors.forename: D I
authors.initials: DI
authors.lastname: Graham
authors.forename: T K
authors.initials: TK
authors.lastname: McIntosh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009336:Necrosis; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases