Heat shock protein 72 expression and microtubule-associated protein 2 disappearance after hypoxia-ischemia in the developing rat brain.
OBJECTIVE
This study was intended to investigate the temporal changes in heat shock protein 72 expression and microtubule-associated protein 2 disappearance in rat brain at 2 different ages after hypoxic-ischemic insult.


METHODS
Both 5-day-old and 14-day-old Wistar rats were subjected to unilateral common carotid artery ligation and hypoxia in 8% oxygen for 2 hours at 33 degrees C. Brain sections were examined sequentially for heat shock protein 72 expression at 0.5, 3, 6, 12, 24, 48, and 72 hours of recovery after hypoxia-ischemia and for microtubule-associated protein 2 disappearance at 0, 24, 48, and 72 hours of recovery and at 7 days of recovery after hypoxia-ischemia. Results of immunohistochemical staining for heat shock protein 72 and microtubule-associated protein 2 were used as markers for detection of early hypoxic-ischemic brain damage. Permanent neuronal damage was assessed with hematoxylin and eosin staining at 7 days after hypoxia.


RESULTS
In 5-day-old rats microtubule-associated protein 2 expression was lost as early as 0 hours after hypoxia-ischemia in the cerebral cortex and hippocampus, with a peak at 48 hours after which expression recovered. Expression of heat shock protein 72 was detected in the ligated hemisphere at 0.5 hours after hypoxia-ischemia and peaked at 6 to 24 hours of recovery. In 14-day-old rats microtubule-associated protein 2 was stained in the cortex at 0 hours after hypoxia-ischemia but gradually disappeared in the cerebral cortex and hippocampus after 24 hours of recovery. The expression of heat shock protein 72 was not detected by 6 hours of recovery in the cerebral cortex and by 3 to 12 hours of recovery in the hippocampus, but heat shock protein 72 was persistently expressed in the cortex and hippocampus after 48 hours of recovery. Neuronal damage was significantly less in 5-day-old rats than in 14-day-old rats.


CONCLUSIONS
In 5-day-old rats hypoxia-ischemia causes earlier changes in heat shock protein 72 and microtubule-associated protein 2 immunostaining results and causes less severe brain damage than in 14-day-old rats.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development*; D002545:Brain Ischemia / Q000378:metabolism*; D002339:Carotid Arteries; D002540:Cerebral Cortex / Q000737:chemistry; D004396:Coloring Agents; D004801:Eosine Yellowish-(YS); D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000032:analysis*; D006416:Hematoxylin; D006624:Hippocampus / Q000737:chemistry; D002534:Hypoxia, Brain / Q000378:metabolism*; D007150:Immunohistochemistry; D008026:Ligation; D008869:Microtubule-Associated Proteins / Q000032:analysis*; D010100:Oxygen / Q000008:administration & dosage; D051381:Rats; D013997:Time Factors