Pre- and post-treatment with MK-801 but not pretreatment alone reduces neocortical damage after focal cerebral ischemia in the rat.
The effect of treatment with the potent, non-competitive NMDA receptor-channel antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a, d] cyclohepten-5,10-imine maleate (MK-801) on ischemia-induced brain damage was studied in a well-characterized model of focal neocortical infarction in spontaneously hypertensive rats. Anesthesia exposure was minimized to the surgical procedure and the infarcts were allowed to mature over a 24-h period. Pretreatment with 5 mg/kg i.p. MK-801 (n = 11 control, n = 12 treated animals) 30 min before induction of focal cerebral ischemia had no statistically significant influence on infarct volumes. However, pre- and post-treatment with MK-801 5 mg/kg i.p. 30 min before induction of ischemia and 2.5 mg/kg each at 8 and 16 h after onset of ischemia, reduced infarct volumes in two separate studies by 29% (investigator J.T., n = 5 control and n = 7 treated animals) and 20% (investigator U.D., n = 8 control and n = 8 treated animals), respectively. The combined reduction in infarct volume in MK-801-treated animals for both investigators was 23% (P = 0.016, ANOVA). The findings indicate a smaller neuroprotective effect of MK-801 in spontaneously hypertensive rats subjected to focal ischemia than in previous reports using normotensive animals.
Dirnagl
U
U
Cerebrovascular Disease Research Center, Cornell University Medical College, New York, NY 10021.
Tanabe
J
J
Pulsinelli
W
W
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001925:Brain Damage, Chronic / Q000209:etiology / Q000517:prevention & control*; D002540:Cerebral Cortex / Q000187:drug effects; D002544:Cerebral Infarction / Q000188:drug therapy; D016291:Dizocilpine Maleate / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D006973:Hypertension / Q000150:complications* / Q000235:genetics; D002546:Ischemic Attack, Transient / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008991:Monitoring, Physiologic; D051381:Rats; D011918:Rats, Inbred SHR; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate