Propofol Pretreatment Attenuates Aquaporin-4 Over-Expression and Alleviates Cerebral Edema After Transient Focal Brain Ischemia Reperfusion in Rats

Cerebral edema is a major threat for stroke victims. Most studies have focused on the neuroprotective activities of propofol, addressing infarct volume rather than cerebral edema. Aquaporin-4 (AQP4) plays an important role in maintaining brain water homeostasis under various neurological insults. We explored the effect of propofol pretreatment on cerebral edema in a rat model of brain ischemia reperfusion and assessed the involvement of AQP4. To induce brain ischemia reperfusion, we introduced a silicone-coated monofilament nylon suture into the origin of the middle cerebral artery, withdrawing it after 90 min. Treatment groups (n = 32), received propofol (0.1 mL x kg(-1) x min(-1)) infusion for 30 min before occlusion; the vehicle group (n = 32) and the sham-operated group (n = 28), which received the intralipid vehicle at the same time and rate. To assess cerebral infarct volume, we used 2, 3, 5-triphenyl-tetrazolium chloride staining; wet-dry weight ratio was the basis for cerebral edema estimation, and we used immunohistochemistry and Western blot to detect AQP4 expression. The wet-dry weight ratio decreased from 86.89% +/- 0.71% in the vehicle group (n = 6) to 72.42% +/- 0.74% in the propofol group (n = 6), corresponding to an average decrease of 16%. In parallel and based on immunohistochemical semi-quantification, the propofol group exhibited remarkable attenuation of AQP4 over-expression in the ischemic border zone compared with the vehicle group: 1.28 +/- 0.03 vs 1.40 +/- 0.05, n = 7, respectively; P < 0.05. Values derived from Western blot quantification were similarly decreased in the propofol group compared to the vehicle group: 20.85% +/- 4.18% vs 31.67% +/- 3.23%, n = 4, respectively; P < 0.05. However, infarct volume and neurologic deficit in postischemic rats in the propofol group were not statistically different from values in the vehicle group. We conclude that prestroke treatment with propofol reduces postischemic cerebral edema in rats, possibly through inhibiting AQP4 over-expression in the boundary zone of ischemia.