Evidence disputing the importance of excitotoxicity in hippocampal neuron death after experimental traumatic brain injury.
The hippocampus is selectively vulnerable to experimental traumatic brain injury (TBI). Beneficial effects of glutamate receptor antagonists and increased extracellular levels of glutamate have suggested that glutamate-mediated excitotoxicity may be responsible for this selective damage. In order to clarify this important issue, we applied a severe parasagittal fluid percussion injury (FPI) to strains of mice shown to be susceptible and resistant to kainic acid (KA)-induced excitotoxic hippocampal damage. Dystrophic neurons were present by 10 min after FPI in the hippocampi of both strains. Damaged hippocampal neurons were absent at 4 days and 7 days. Additionally, there was no significant difference (p = 1.00) in CA3 neuron survival between KA-susceptible and -resistant mice at 4 days. In conclusion, excitotoxicity does not significantly contribute to hippocampal neuron loss after FPI and, in contrast to classic studies of excitotoxicity in vivo, the pattern of hippocampal cell death after TBI is extremely acute.
Carbonell
W S
WS
Department of Neurological Surgery, University of Washington School of Medicine, Seattle, USA.
Grady
M S
MS
D000818:Animals; D001930:Brain Injuries / Q000235:genetics / Q000473:pathology*; D002470:Cell Survival / Q000235:genetics; D018690:Excitatory Amino Acid Agonists; D005089:Exocytosis / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000293:injuries*; D007608:Kainic Acid; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000473:pathology*
D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid