The neuroprotective actions of kynurenic acid and MK-801 in gerbils are synergistic and not related to hypothermia

Eur J Pharmacol. 1990 Feb 6;176(2):143-9. doi: 10.1016/0014-2999(90)90522-8.

Abstract

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).

MeSH terms

  • Animals
  • Body Temperature
  • Brain / pathology
  • Carotid Arteries / physiology
  • Dibenzocycloheptenes / pharmacology*
  • Dizocilpine Maleate
  • Drug Synergism
  • Gerbillinae
  • Ischemic Attack, Transient / pathology
  • Ischemic Attack, Transient / prevention & control*
  • Kynurenic Acid / pharmacology*
  • Neurons / drug effects
  • Pyramidal Tracts / cytology
  • Pyramidal Tracts / drug effects

Substances

  • Dibenzocycloheptenes
  • Dizocilpine Maleate
  • Kynurenic Acid