%0 Journal Article
%T Flutamide Enhances Neuroprotective Effects of Testosterone during Experimental Cerebral Ischemia in Male Rats
%A Hamed Fanaei
%A Hamid Reza Sadeghipour
%A Seyed Morteza Karimian
%A Gholamreza Hassanzade
%J ISRN Neurology
%D 2013
%R 10.1155/2013/592398
%X Testosterone has been shown to worsen histological and neurological impairment during cerebral ischemia in animal models. Cell culture studies revealed that testosterone is implicated in protecting neural and glial cells against insults, and they started to elucidate testosterone pathways that underlie these protective effects. These studies support the hypothesis that testosterone can be neuroprotective throughout an episode of cerebral ischemia. Therefore, we evaluated the mechanisms underlying the shift between testosterone protective and deleterious effects via block testosterone aromatization and androgen receptors in rats subjected to 60-minute middle cerebral artery occlusion. Fifty rats were divided into five equal groups: gonadally intact male; castrated male; intact maleˋ+ˋflutamide; intact maleˋ+ˋletrozole; intact maleˋ+ˋcombination flutamide and letrozole. Our results indicated that castration has the ability to reduce histological damage and to improve neurological score 24 hours after middle cerebral artery occlusion. Moreover, flutamide improved histologic and neurological impairment better than castration. Letrozole induced increases in striatal infarct volume and seizures in gonadally intact rats. Combination of flutamide and letrozole showed that letrozole can reverse beneficial effects of flutamide. In conclusion, it seems that the beneficial effects of flutamide are the prevention of the deleterious effects and enhancement of neuroprotective effects of testosterone during cerebral ischemia. 1. Introduction Stroke is a great reason of disability and death throughout the world [1]. Nowadays treatments are not very effective to reduce brain ischemia, whereas size of the infarct area will affect on patient＊s chance of recovery from a stroke and it will keep growing if treatments are not appropriate [1每4]. So, for reducing damage we need to find more effective treatments. Among risk factors, sex has prominent role in stroke [5每8]. Epidemiological studies have shown that overall incidence of stroke is higher in men relative to age-matched women in most countries [9每12]. Present evidence suggests that mechanisms of cell death and neuroprotection are not similar and equal in males and females [9, 13, 14]. A large part of this difference between sexes is attributed to sex steroids [14每18]. Previous studies demonstrate that estrogen and progesterone give protection against cerebral ischemia by several mechanisms [19每23]. On the other hand, data about androgens are sparse and controversial [9, 18, 24, 25]. Human studies suggested male
%U http://www.hindawi.com/journals/isrn.neurology/2013/592398/