The neuroprotective actions of kynurenic acid and MK-801 in gerbils are synergistic and not related to hypothermia.
The broad spectrum excitatory amino acid antagonist, kynurenic acid was evaluated in a transient forebrain ischaemia model in gerbils. When administered i.p., 15 min prior to a 5 min period of ischaemia, a dose-related neuroprotective effect was seen with 800 mg/kg of kynurenic acid showing very good protection. A combination of kynurenic acid (200 or 400 mg/kg) and MK-801 (0.1 mg/kg) gave a synergistic neuroprotective effect. Neither kynurenic acid (200 or 400 mg/kg) nor MK-801 (0.3 mg/kg) was neuroprotective when administered by itself 30 min post-ischaemically, but when co-administered significant protection of the CA1 pyramidal neurones of the hippocampus was seen. In addition, we examined the effect of maintaining core body temperature on the neuroprotective action of MK-801 and kynurenic acid following the suggestion that it was a hypothermic effect of MK-801 which resulted in neuroprotection in gerbils. When the body temperature of the gerbils was maintained at 37 degrees C for a period of 24 h it did not affect the neuroprotective action of MK-801 (0.1 or 10 mg/kg) or kynurenic acid (200 mg/kg).
Gill
R
R
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, U.K.
Woodruff
G N
GN
D000818:Animals; D001831:Body Temperature; D001921:Brain / Q000473:pathology; D002339:Carotid Arteries / Q000502:physiology; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D004357:Drug Synergism; D005849:Gerbillinae; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000517:prevention & control*; D007736:Kynurenic Acid / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D011712:Pyramidal Tracts / Q000166:cytology / Q000187:drug effects
D003986:Dibenzocycloheptenes; D016291:Dizocilpine Maleate; D007736:Kynurenic Acid