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.
Sopala
M
M
Department of Pharmacology, Merz+Co., Eckenheimer Landstrasse 100-104, 60318 Frankfurt/, Main, Germany.
Frankiewicz
T
T
Parsons
C
C
Danysz
W
W
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications / Q000503:physiopathology*; D002539:Cerebral Arterial Diseases / Q000150:complications / Q000503:physiopathology*; D003517:Cyclopentanes / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000503:physiopathology*; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D020768:Middle Cerebral Artery / Q000503:physiopathology*; D009473:Neuronal Plasticity; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*
D003517:Cyclopentanes; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; C114144:neramexane