Pharmacological protection of reoxygenation damage to in vitro brain slice tissue.
Pharmacological protection of central neural function against damage by hypoxia and reoxygenation was studied electrophysiologically and biochemically in hippocampal brain slices. Hypoxia causes a loss of both orthodromically and antidromically evoked potentials in CA1 pyramidal cell neurons. Damage due to hypoxia lasting more than 10 min cannot be restored by reoxygenation. Following pretreatment with methylprednisolone (10(-5) M), indomethacin (10(-5) M) or allopurinol (10(-5) M), reoxygenation after 10 min of hypoxia resulted in complete recovery of the evoked activity. Na+,K+-ATPase activity was not reduced by 10 min of hypoxia, but was reduced by 50% during the first 10 min of subsequent reoxygenation. Allopurinol (10(-5) M) protected against loss of this enzyme activity. The protective action by these drugs of both electrophysiological and biochemical aspects of neural function is consistent with the hypothesis that secondary ischemic damage is caused by the formation of oxygen-derived free radicals during reperfusion.
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002470:Cell Survival; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000503:physiopathology*; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000473:pathology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013997:Time Factors
D000493:Allopurinol; D000254:Sodium-Potassium-Exchanging ATPase; D008775:Methylprednisolone; D007213:Indomethacin