BACKGROUND: Neuronal cell death after brain ischemia occurs predominately by necrosis, whereas only a minor fraction of cell death may occur through apoptosis. Authors investigated DNA fragmentation and apoptotic morphology in the brain cell to determine whether apoptosis contributes to the progression of an ischmic lesion. This study was conducted to determine the effects of dexamethasone and hypothermia on moderate brain ischemic injury by middle cerebral artery occlusion (MCAO) in rats. METHODS: Thirty Sprague-Dawley rats (220 - 280 g) were used. Anesthesia was induced and maintained with isoflurane in oxygen. MCAO was induced by intraluminal monofilament nylon. All rats were divided randomly into three groups. In group I (n = 10), normal saline 1 ml was injected intravenously 10 minutes before MCAO. In group II (n = 10), dexamethasone 3 mg/kg was administered and in group III (n = 10), body temperature was maintained at 32degreesC. After 60 minutes of MCAO, all rats that recovered from anesthesia were returned to cages. After 24 hour reperfusion, brain tissue was quickly removed and cerebral hemispheres were separated. Lesion volumes were measured by TTC staining. TUNEL reactivity was examined in the cortical infarction lesion, and rat brain DNA was run on agarose gel electrophoresis to detect DNA fragmentation. RESULTS: Apoptosis and DNA fragmentation in the nucleus developed in the hippocampal area after transient ischemia in rats. Dexamethasone did not prevent the development of apoptosis and DNA fragmentation in transient brain ischemic rats. Moderate hypothermia could prevent the development of apoptosis and DNA fragmentation in transient brain ischemic rat. CONCLUSIONS: Apoptosis may represent a mode of ischemic cell death, and dexamethasone couldn't prevent apoptotic change in the ischemic brain insult. Moderate hypothermia (32degreesC) was a specifically effective procedure to reduce the development of apoptotic change in ischemic insults.