Middle cerebral artery occlusion produces secondary, remote impairment in hippocampal plasticity of rats - involvement of N-methyl-D-aspartate receptors?

There is increasing evidence that focal cerebral ischaemia produces remote functional alterations that may substantially contribute to the post-stroke neurological outcome. Changes initially limited to peri-infarct areas may evolve and spread via transneuronal connections to other structures. In the present study we investigated whether focal ischaemia produced by 2-h occlusion of the middle cerebral artery (MCAo) in SD rats may influence the physiological function of the hippocampus. Three days later in vitro long-term potentiation (LTP) was studied in hippocampal slices from ipsi- and contralateral hemispheres. In rats with MCAo LTP was not-inducible in the ipsilateral hippocampus, while the contralateral side expressed stable potentiation (6.6+/-4.1 vs. 35. 0+/-8.0%, respectively). Treatment with 6-h i.v. infusion of an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MRZ 2/579 starting at reperfusion not only preserved but additionally enhanced ipsilateral LTP, while a slight insignificant decrease was observed in the contralateral side (77.0+/-18.4 vs. 20.8+/-6.5%). The study demonstrates post-stroke functional changes in the hippocampus that can be modulated by NMDA receptor antagonists.