Neuroprotective Effects of GSK-3β Inhibition in Cerebral Ischemia

Rats were given free access to food and water in optimal surroundings before the operation. Adult rats were divided randomly into 11 groups. Under normal conditions, the groups were: normal group, scramble group, GSK-3β siRNA (siRNA) group, SB216763 (SB) group (20 μg/kg, intracerebroventricular injection), and the LiCl group (50 mg/kg, intraperitoneal injection). After MCAO/R, the groups were: sham-operated (sham) group, MCAO/R group, scramble + MCAO/R group, GSK-3β siRNA (siRNA) + MCAO/R group, SB + MCAO/R group, and the LiCl MCAO/R group. Transient cerebral ischemia (MCAO) was described in detail in our previous study33 (link)34 (link). Rats were anesthetized with chloral hydrate (350 mg/kg, intraperitoneal injection) and subjected to the operation. A nylon filament (diameter 0.24–0.28 mm) was inserted into the middle cerebral artery for 1 h. The nylon filament was carefully removed to allow blood to return to the ischemic artery, and then was sutured to establish reperfusion. Regional cerebral blood flow was detected by an ultrasonic blood flow meter before ischemia, during MCAO, and during reperfusion. Sham-operated rats were subjected to the same surgical procedure as MCAO rats except for occlusion of the common carotid arteries. Animals that had blood reperfusion below 70% or that died during reperfusion were excluded from analysis.