Characterization of cellular and neurological damage following unilateral hypoxia/ischemia.
Rodent models of stroke are often used to investigate the mechanisms that lead to ischemic neuronal damage. In this study, we used a model of cerebral hypoxia with ischemia to produce unilateral damage in C57Bl/6 mice. Lesion volume, ascertained by TTC staining, increased with longer durations of hypoxia. Additionally, cresyl violet, TUNEL, and FluoroJade staining showed a statistically significant increase in cellular damage in the ipsilateral cortex, CA1 pyramidal layer, and dentate gyrus of the hippocampus of ipsilateral hypoxic/ischemic tissue versus sham tissue. Astrocyte reactivity, determined by GFAP staining, was significantly higher in the ipsilateral H/I cortex and contralateral hippocampus compared to sham cortex and hippocampus, respectively. Increased microglia activation was evident in the H/I-treated cortex and hippocampus versus sham cortex and hippocampus, particularly within areas undergoing degeneration. To examine whether this model produces motor deficits, a battery of tests were administered before and after hypoxia. Following 45 min H/I, locomotor activity, rotarod performance and performance on an inverted wire hang test were all significantly decreased. These data indicate that the histological evidence of neuronal damage is consistent with functional deficits and suggest that this model may be useful for investigating strategies designed to protect neurons from hypoxia/ischemia-induced damage.
Olson
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EE
Emory University, Department of Cell Biology, Whitehead Biomedical Research Building, 615 Michael Street, Atlanta, GA, 30322, USA.
McKeon
R J
RJ
D000818:Animals; D001522:Behavior, Animal; D048588:Benzoxazines; D020520:Brain Infarction / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D005456:Fluorescent Dyes; D007839:Functional Laterality / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D010078:Oxazines; D011597:Psychomotor Performance / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D045442:Rotarod Performance Test / Q000379:methods; D013266:Stilbamidines; D013778:Tetrazolium Salts; D013997:Time Factors
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D048588:Benzoxazines; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein; D016177:Macrophage-1 Antigen; D010078:Oxazines; D013266:Stilbamidines; D013778:Tetrazolium Salts; C028911:cresyl violet; C009591:triphenyltetrazolium