Effects of hyperthermia on the effectiveness of MK-801 treatment in the gerbil hippocampus following transient forebrain ischemia.
The effects of dizocilipine maleate (MK-801), a noncompetitive N-methyl-D-aspartate (NMDA) receptor/channel antagonist, were tested on the dysfunction of neurotransmitter and signal transduction systems and morphological damage 7 days after transient forebrain ischemia in gerbils. Neurotransmitter system (adenosine A1, muscarinic cholinergic receptor) and signal transduction system (inositol 1,4,5-trisphosphate receptor: IP3, protein kinase C: PKC, L-type calcium channels) binding sites were mapped by in vitro quantitative receptor autoradiography. All ligands used in the present study decreased significantly in the CA1 subfield 7 days after ischemia. In normothermic animals, pretreatment with MK-801 failed to protect against decreased receptor binding in the hippocampus 7 days after ischemia. Moreover, in a morphological study, pre- and posttreatment of MK-801 failed to show protective effects against ischemic neuronal damage. On the other hand, pretreatment of MK-801, without maintaining body temperature, prevented the neuronal death of CA1 subfield 7 days after ischemia. These results weaken the hypothesis that NMDA receptor/channel may play a pivotal role in the pathogenesis of neuronal damage after transient forebrain ischemia.
Hara
H
H
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Onodera
H
H
Kogure
K
K
D000818:Animals; D001345:Autoradiography; D001831:Body Temperature / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D006979:Hyperthermia, Induced; D002546:Ischemic Attack, Transient / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000502:physiology; D011712:Pyramidal Tracts / Q000473:pathology; D015424:Reperfusion; D015398:Signal Transduction / Q000502:physiology
D016291:Dizocilpine Maleate