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 minperiod 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°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).