The Neuroprotective Effects of Transdermal Nitroglycerin and Intraperitoneal Phenytoin on Ischemic-Hypoxic Injury in Developing Rat Brains

ABSTRACT

The goal of this study was to evaluate neuroprotective effects of nitroglycerin and phenytom using in the developing rat brains Seven days old Sprague-Dawley rats underwent right carotid ligation followed by 8% 02 exposure (humidified, balanced with mtrogen) for 3 hours under the halothane anesthesia (control group, N=58). Body temperature of rats was accurately controlled before and during hypoxia. In nitroglycerin treated group (N=33), nitroglycerin was delivered chronically via patches (in escalating doses to 4mg/kg/hr) for 36hrs before and 48hrs postischemia. Phenytoin treated group(N=17) received intraperitoneal phenytoin(30mg/kg) before ischemia. Combined treated group(N=31) with nitroglycerin and phenytoin received two compounds with same method as above. Animals. Sacrificed one week later and histopathological evaluation for ischernic neuronal damage were conducted employing hemat,oxylin eosin staining and measurements of the hemispheric weight difference. Phenytoin was effective in reducing neuronal damage in terms of weight comparison(24+2.4%, atrophy in control vs. 5+2.9% in phnytoin group, p<0.001) and ischemic changes in hippocampal area(p<0.05 in CA1, CA2, and CA3 area). Transdermal nitroglycerin did not show any beneficial effects compared with control group(23+3.0% in nitroglycerin group vs. 24+2.5% in control). Combined treated group showed neuroprotection on weight comparison(24+2.4% in control vs 4+1.8% in combined group, p<0.001) and ischemic changes in hippocampal area(p<0.05 in CA1, CAZ and CA3 area) but dldnot show any additional neuroprotective effects compared with phenytoin group on weight comparison and histological changes. These data suggest that the degree of the injury from hypoxic-iwhemic insults of developing rat brain may be reduced by the compounds that modulate voltagedependent sodium channels such as phenytom but not by nitroglycein.