Effects of propofol on neuronal apoptosis and aquaporin-4 expression in a rat model of traumatic brain injury

BACKGROUND: Several studies have demonstrated that propofol exhibits protective effects in the central nervous system. OBJECTIVE: To observe the effects of propofol on neuronal apoptosis and aquaporin-4 (AQP-4) expression in a rat model of traumatic brain injury and to further investigate the mechanisms of action. DESIGN, TIME AND SETTING: The present neuronal, pathomorphological experiment was performed at the Institute of Cerebrovascular Disease, Qingdao University Medical College between April 2007 and March 2008. MATERIALS: Traumatic brain injury was induced by free falling objects in 150 healthy, male, Wistar rats. Propotol was produced by AstraZeaeca, China. Rabbit anti-rat AQP-4 polyclonal antibody, SABC inununohistochemistry kit, and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling (TUNEL) kit were purchased from Wuhan Boster Bioengineering Co., Ltd., China. METHODS: All 150 rats were randomly and evenly divided into lesion-only and propofol-treated groups. One hour after traumatic brain injury, propofol-treated animals received 1% propofol (10 mg/kg) through the caudal vein, followed by a sustained perfusion of 30 mg/kg propofol per hour for 2 hours, while the lesion-only group received equal volumes of physiological saline in parallel. MAIN OUTCOME MEASURES: At 6, 12, 24, 48, and 72 hours after traumatic brain injury, morphological changes in the peritraumatic and adjacent brain areas were analyzed in all rats by hematoxylin-eosin (HE) staining. In addition, cellular apoptosis was detected by TUNEL assay and the number of AQP-4-positive cells was determined by immunohistochemistry techniques. Brain water content was calculated as the ratio of dry to wet tissue weight. RESULTS: HE staining results demonstrated that, in the lesion-only group, the peritraumatic area exhibited neuronal and glial cell necrosis and disintegration. The adjacent area displayed swollen neuronal perikarya and vascular endothelial cells, cellular edema, and a small amount of proliferating glial cells. In contrast, these pathological changes were noticeably alleviated in the peritraumatic and adjacent areas of propofol-treated animals. Compared with the lesion-only group, the number of apoptotic cells was significantly decreased in the propofol-treated group at each time point after traumatic brain injury, in particular at 24 and 48 hours (P < 0.05-0.01 ). In the lesion-only group, AQP-4 expression began to increase at 6 hours after traumatic brain injury, reached a peak level at 24-48 hours, and began to decrease by 72 hours. In the propofol-treated group, the number of AQP-4 positive cells was significantly less than the lesion-only group. This was the case at all time points, in particular at 12 and 24 hours (P < 0.01-0.05). CONCLUSION: Propofol can downregulate neuronal apoptosis and AQP-4 expression in rats following traumatic brain injury, in particular at 24-48 hours.