EPILEPTIFORM ACTIVITY AND HIPPOCAMPAL DAMAGE PRODUCED BY INTRAHIPPOCAMPAL INJECTION OF GUANIDINOSUCCINIC ACID IN RAT

Guanidinosuccinic acid (GSA) is a guanidino compound found in mammalia n central nervous system and physiological fluids. Its level has been found to be greatly increased in serum and cerebrospinal fluid of pati ents with renal failure, and the compound is suggested to play a role in uremic encephalopathy. In this report we examined the behavioral, e lectrographic and morphological effects of intrahippocampal GSA inject ion in unanesthetized rats. Intrahippocampal administration of 2 mu l GSA solution (3.5 nM) was followed by behavior observation, and electr ohippocampographic and electrocorticographic recording. GSA-injected a nimals showed partial clonic seizures leading to generalized clonic se izures, and eventually status epilepticus. These were accompanied by e pileptiform electrographic discharges. During generalized clonic seizu res, the electrohippocampogram showed arythmic bursting spikes. Epilep tiform electric activity persisted even after the generalized clonic c onvulsions had stopped, and lasted until the animals were killed, 5 da ys following injection. Microscopic examination of brain slices of the se rats revealed severe neural damage in CAI area of hippocampus, Trea tment of rats with the non-competitive NMDA receptor antagonist ketami ne prevented both partial and generalized clonic seizures, epileptifor m electrographic discharges, and GSA-induced hippocampal damage.