Neuroprotective effects of MK801 against cerebral ischemia-reperfusion injury

During Cerebral ischemia/reperfusion injury (I/RI), NMDA receptor activity increases, leading to an excessive entry of sodium and calcium, which damages neurons. Therefore, deletion of NMDA receptor subunits may reduce cell death induced by acute brain injury. MK801 is a non-competitive NMDA receptor antagonist that can block NMDA ion channels. In this experimental study, Wistar rats were divided into 6 groups:Sham, I/R, I/R+NMDA (0.5 mg/kg, IV), I/R+MK801 (0.5 mg/kg, IV), I/R+NMDA+ electrophysiology, and I/R+MK801+ electrophysiology. The acute cerebral ischemic injury was induced in rats by occlusion of the common and vertebral carotids for 15 minutes followed by 6 h reperfusion. The rats were treated with MK801 and NMDA (0.5 mg/kg, IV) after 30 minutes of reperfusion. Nissl, H&E staining, and Western blot were used.In addition, the electrophysiological changes in the CA1 pyramidal neuron were evaluated. The cerebral I/R injury model significantly causes damage to pyramidal neurons in the CA1 area in H&E staining (P<0.0001), a decrease in the expression of BDNF, c-fos, phosphorylated CREB/CREB proteins (P<0.0001) than the sham group. The NMDA antagonist, MK801, significantly improved the number of living brain cells in the hippocampus compared to the ischemia group (P<0.01). In addition, the use of MK801 in rats with ischemia caused an increase in BDNF, c-fos (P<0.0001), phosphorylated CREB/CREB factors (P<0.001), and a decrease in caspase 3 (P<0.0001) compared to the ischemia group. In addition, electrophysiological data showed that NMDA antagonist increases the firing rate of CA1 pyramidal neurons compared to the reperfusion phase (P<0.05).