Nimodipine improves spatial memory via inhibiting NLRP3 inflammasome activation in a rat model of focal cerebral ischemia

Author(s): Yiwen Zhang*, Hongbo Pang, Yan Xiong
Abstract: Impairment of spatial memory is a common complication after cerebral ischemia. This study was performed to evaluate the neuroprotective effect of nimodipine on spatial memory in a rat model of focal cerebral ischemia. A rat model of focal cerebral ischemia was induced in Sprague-Dawley male rats by middle cerebral artery occlusion (MCAO). The model rats were treated with intracarotid infusion of 40 μg/kg/30 min nimodipine (started 15 min before recirculation and maintained until 15 min after recirculation) plus intraperitoneal injection of 2 mg/kg nimodipine daily in the next three weeks. The negative control rats and sham rats received only saline. The spatial memory was then assessed by the Morris water maze. Histological changes of brain were assessed by TUNEL staining and Golgi staining. The NLRP3 inflammasome activation status was assessed by Western blot. Water maze test showed that spatial learning and memory abilities were impaired by MCAO. Nimodipine treatment could reduce escape latency in the spatial acquisition trail and increase cross duration in probe quadrant. Moreover, nimodipine attenuated neuron cell apoptosis in the hippocampus area. Golgi-staining showed that nimodipine also improved neuron morphology in the hippocampus and increased dentritic spine density in the CA1 area. In addition, nimodipine reduced expression of NLRP3, cleaved caspase-1, IL-1β, and IL-18, indicating that NLRP3 inflammasome activation was attenuated. In conclusion, nimodipine has neuroprotective effect in rat model of focal cerebral ischemia by inhibiting NLRP3 inflammasome activation. 

Keywords: focal cerebral ischemia, NLRP3 inflammasome, Morris water maze, hippocampus, nimodipine
Adv.Bio.Med.: 2019, Vol.4(No.2),pp:42-56