engleski

The effect of MK-801 on the Na+, K+-ATPase activity and ERK activation in rats exposed to global cerebral ischaemia

Aims: We examined the effects of MK-801 on the Na+, K+-ATPase activity and ERK activation in the rat hippocampal tissue after exposure to global cerebral ischaemia of 20 min duration. Procedure: The enzymatic activity and ERK activation were measured at different time points after ischaemia (30 min: 1: 6: 12: 24: 72 and 168 h for the Na+, K+-ATPase activity measurements/5 and 10 min: 1: 6 and 12 h for ERK activation) in control animals such as in the ischaemic animals pretreated with different doses of MK-801 (0.1: 0.3. 1.0 and 3.0 mg/kg), 30 min before exposure to ischaemia. Results: It was found that global cerebral ischaemia induced a statistically significant decrease in Na+, K+-ATPase activity starting from 1 to 168 h of reperfusion. Maximal enzymatic inhibition was obtained 24 h after ischaemic damage. The activation signal of JNK was detected 5 min up to 12 h after ischaemia, but maximal activation was registered after 1 h of reperfusion. Pretreatment with 1.0 or 3.0 mg/kg of MK-801 prevented the decrease of the Na+, K+- ATPase activity and preserved the level of JNK activation in all experimental groups of the ischaemic animals. Conclusions: Decrease in Na+, K+-ATPase activity such as ERK activation are evident during different periods of reperfusion injury after global cerebral ischaemia. Pretreatment with MK-801 prevented changes mentioned above and indicated its possible beneficial role in the treatment of severe brain ischaemia.

rat; hippocampus; MK-801; Na+; K+-ATPase; ERK; JNK

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