Effects Of Mild Hypothermia On Brain Edema And HIF-1α,VEGF Expression Following Intracerebral Hemorrhage In Rats

Objective To explore the possible mechanism of mild hypothermia to inhibit the formation of brain edema by studying the effect of mild hypothermia on HIF-1α,VEGF expression after ICH in rats.Methods To make an intracerebral hemorrhage (ICH) model in rats by autologous femoral artery blood, male Sprague-Dawley rats were positioned in a stereotaxic frame. ICH was induced in the rats: 50μl antilogous femoral artery blood was sampled and then infused stereotacticlly into the right caudate nucleus through a needle(coordinates: 1mm anterior, 5.5 mm ventral, and 3.0mm lateral to bregma) .The rats were divided into 3 groups at random: the sham operation group, the normothermia group and the mild hypothermia group. The brains were collected to measure different items at the peak time of brain edema(48h). The neurobehavioral scores and histological morphological damage were investigated; brain water content and BBB permeability were tested; immunohistochemistory and RT-PCR were performed to detect the relations among the HIF-1α,VEGF expression and brain edema.Results 1. In ICH group, the rats appeared left-side hemiplegia after waking up. In the normothermia group, the neurological deficit scores leveled the highest at 48h after operation in the Longa and Berderson testing methods, until all the rats recovered and the scores fell to the lowest at 7d.2.By HE staining, the ipsilateral side was divided into hematoma area,perihematoma area(brain edema) and normal area. At 48h after operation, erythrocytes were intact; the brain tissues around hematoma were highly swollen with pale cytoplasm; the neurons were degenerated with vague nuclear and disappearing nissl bodies.3. In the normothermia group, the brain water content and the BBB permeability to Evans'blue increased highest at 48h,and HIF-1αand VEGF immunoreactivity were detected in perihematoma. The expression of VEGF mRNA was detected by RT-PCR analysis.4. Mild hypothermia significantly reduced the brain edema volume and ameliorated BBB injury. Mild hypothermia reduced HIF-1α,VEGF expression and suppressed VEGF mRNA transcript.Conclusions 1. ICH model in rats by infusing autologous artery blood is reproductile. Following the hemorrhage there appeare some changes on behaviors. 2. At 48hr after ICH, with rCBF in perihematoma being reduced, HIF-1αexpression increases, which induces VEGF mRNA and then VEGF expression. VEGF demolishes BBB integrity and resultes in brain edema.3. Ischemia factor involves in the pathological process of brain edema.4. It is assumed that the inhibition of HIF-1α,VEGF expression and the reduction of brain edema may be one of the mechanisms of hypothermic neuroprotection.