Reduction of perinatal hypoxic-ischemic brain damage with allopurinol.
Cytotoxic free radicals are generated during cerebral hypoxia-ischemia and reperfusion. We studied the efficacy of allopurinol, a xanthine oxidase inhibitor and free radical scavenger, in reducing posthypoxic-ischemic damage in the developing brain of 7-d-old rat pups. Hypoxic-ischemic injury to the right cerebral hemisphere was produced by ligation of the right common carotid artery followed by 3 h of hypoxia with 8% oxygen. Thirty to 45 min before the hypoxia, the rats received either allopurinol (dose = 130-138 mg/kg) or an equal vol of saline (0.2 mL). Some pups were killed at 42 h of recovery for measurement of cerebral hemispheric water content, whereas others were killed at 30 or more d for neuropathologic examination. A total of 18 allopurinol treated rats had significantly less water content in the right hemisphere (89.07 +/- 0.32%) than 23 saline-treated animals (91.64 +/- 0.25%, mean +/- SEM, p less than 0.0001). Rank scoring of neuropathologic alterations revealed that the allopurinol treated rats were less damaged (p = 0.001). Only two of 13 brains from the allopurinol group suffered infarction compared to 10 of the 14 saline-treated animals. The results indicate that allopurinol reduces both cerebral edema and the extent of perinatal hypoxic-ischemic brain damage.
Palmer
C
C
Department of Pediatrics, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Vannucci
R C
RC
Towfighi
J
J
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001834:Body Water / Q000187:drug effects / Q000378:metabolism; D001929:Brain Edema / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005609:Free Radicals; D002534:Hypoxia, Brain / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D005609:Free Radicals; D000493:Allopurinol