Effects of the 21-amino steroid tirilazad mesylate (U-74006F) on brain damage and edema after perinatal hypoxia-ischemia in the rat.
Using 7-d-old rat pups, the neuroprotective efficacy of the lipid peroxidation inhibitor tirilazad mesylate (U-74006F) was tested in a model of perinatal hypoxic-ischemic (HI) brain damage. The experimental protocol was divided into five parts: 1) pre- plus post-HI treatment or 2) only post-HI treatment with tirilazad (7.5 mg/kg intraperitoneally) or vehicle with evaluation of hemispheric weight deficit 14 d after the insult; 3) post-HI treatment with tirilazad or vehicle with histopathologic evaluation 14 d after the insult; 4) pre- plus post-HI treatment; or 5) posthypoxic treatment with tirilazad or vehicle with evaluation of brain edema 20 h after the insult. In the pre- plus post-HI treatment group, the mean left hemispheric weight deficit was 20.7% +/- 17.8 (mean +/- SD) in tirilazad-treated rats and 27.5% +/- 20.4 in vehicle-treated rats (p = 0.032). Corresponding values for the post-HI treated animals were 19.6% +/- 16.0 and 28.6% +/- 15.4 (p = 0.043). Histopathologic injury assessed as pathology score on a scale of 0-5 was less extensive in tirilazad-treated animals compared with controls (p = 0.038). There was a significant increase in water content in the HI hemisphere compared with the contralateral (hypoxic) hemispheres in tirilazad- and vehicle-treated animals. This increase of water content in the HI hemispheres did not differ between tirilazad- and vehicle-treated animals. The lipid peroxidation inhibitor tirilazad administered after perinatal HI reduced brain damage by 30%, but no effect was found on early postinsult edema.
Bågenholm
R
R
Department of Physiology and Pharmacology, Göteborg University, Sweden.
Andiné
P
P
Hagberg
H
H
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D001925:Brain Damage, Chronic / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D001929:Brain Edema / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D016166:Free Radical Scavengers / Q000494:pharmacology*; D002534:Hypoxia, Brain / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011281:Pregnatrienes / Q000494:pharmacology*; D051381:Rats; D011920:Rats, Inbred WF; D017207:Rats, Sprague-Dawley; D013223:Statistics as Topic
D000975:Antioxidants; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D011281:Pregnatrienes; C053355:tirilazad