Global
ischemia, induced in Mongolian gerbils by bilateral occlusion of the carotid arteries for 5 min, produced a significant increase in locomotor activity at 1 day post-occlusion and a severe loss of hippocampal CA1 neurons at 4 days post-occlusion. To explore the pharmacological relationship between
ischemia-induced hypermotility and CA1 cell death in the hippocampus, we evaluated the efficacy of diverse classes of putative
neuroprotective agents for preventing hypermotility and delayed neuronal death. Administration of any
drug 30 min before global
ischemia dose-dependently, and with similar potency, ameliorated both hippocampal delayed neuronal death and locomotor hyperactivity, with a rank order:
tacrolimus (
FK506)>
nizofenone>clonindine>
dizocilpine (
MK-801)>6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione hydrochloride (
YM90K)>
phencyclidine>
pentobarbital>2-(4-(p-fluorobenzoyl)-piperidin-1-yl)-2'-acetonaphthone hydrochloride (
E-2001)>cis-(+/-)-4-phosphonomethyl-2-
piperidine carboxylic acid (CGS19755)>3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide (
U-50,488H)>
piroxicam>
eliprodil>
vinpocetine. Furthermore, potencies of the protective effect on delayed neuronal death and inhibitory effects on hypermotility were closely correlated (r=0.98). These results suggest that post-ischemic CA1 injury and hypermotility share common mechanisms, and further imply that it is possible to predict the neuroprotective efficacy of drugs more easily by examining the inhibitory effects on post-ischemic hypermotility in global
ischemia model in gerbils.