Allopurinol and dimethylthiourea reduce brain infarction following middle cerebral artery occlusion in rats.

Abstract

Free radicals have been shown to play an important role in ischemia-reperfusion injury in several organ systems; however, the role of free radicals in central nervous system ischemia has been less well studied. Many potential free radical-generating systems exist. The primary products of these reactions, superoxide and hydrogen peroxide, may combine to produce hydroxyl radicals. Of the many potential sources of free radical generation, the enzyme xanthine oxidase has been shown to be important in ischemia in noncerebral tissue. We investigated the effect of the hydroxyl radical scavenger dimethylthiourea and the xanthine oxidase inhibitor allopurinol on infarct volume in a model of continuous partial ischemia. Male Sprague-Dawley rats were treated with dimethylthiourea or allopurinol before middle cerebral artery occlusion. Infarct volume was measured by triphenyltetrazolium chloride staining of brains removed 3 or 24 hours after occlusion. Stroke volume was reduced by 30% after dimethylthiourea treatment and by 32-35% after allopurinol treatment. At 24 hours after stroke, cortical tissue was more effectively protected than caudate tissue with both agents. Pretreatment with dimethylthiourea and allopurinol also significantly reduced cerebral edema formation and improved blood-brain barrier function as measured by fluorescein uptake. Our results imply that hydroxyl radicals are important in tissue injury secondary to partial cerebral ischemia and that xanthine oxidase may be the primary source of these radicals. (Stroke 1989;20:488-494)

Dihydrolipoate Reduces Neuronal Injury after Cerebral Ischemia

“…In accordance with the results previously re ported by Martz et al (1989), dimethylthiourea (750 mg/kg) significantly reduced the cortical and the to tal infarct volume in this model. The cortical infarct volume was 45.7 ± 16.5 mm 3 in drug-treated rats compared with 79.3 ± 22.6 mm 3 in control rats, and the total infarct volume was 59.5 ± 18.6 mm 3 in drug-treated rats compared with 96.8 ± 29.0 mm 3 in controls (Fig.…”

Oxidants, antioxidants and the ischemic brain

“…Despite this, studies employing the requisite physiological control and longterm outcome analysis of effects of xanthine oxidase inhibitors on post-ischemic behavior and histology have not been performed. The results from short-term outcome studies in adult rats have been mixed (Lindsay et al, 1991;Martz et al, 1989). More encouraging results have been observed in perinatal brain (Palmer et al, 1993(Palmer et al, , 1990van Bel et al, 1998), but no long-term outcome studies have been reported.…”

Olmesartan reduces oxidative stress in the brain of stroke-prone spontaneously hypertensive rats assessed by an in vivo ESR method

“…Experiments of the in vivo ESR spectroscopy were conducted with pharmacological interventions; pretreatment with apocynin 31 (Sigma, 5 mg kg À1 , intravenous) 20 mins before in vivo ESR spectroscopy, the use of MC-PROXYL (0.33 mmol per kg body weight) spin probe solution that contained dimethylthiourea 32 (Sigma, 1.0 mmol per kg body weight), or combination of these two interventions. Pretreatment with allopurinol 33 (Sigma, 100 mg kg À1 , intraperitoneal) was also performed 30 min before in vivo ESR spectroscopy.…”