Neuronal Cell Death in the Contralateral Hippocampus after Unilateral Hippocampal Kainic Acid-induced Seizure in Rats / 대한간질학회지

BACKGROUND: The recurrent temporal lobe epilepsy induces contralateral cell damage and secondary epileptogenesis in the contralateral hippocampus of rats. This phenomenon is fairly constant and has been used as a model of human temporal lobe epilepsy. It is necessary to understand this patho-mechanism in order to prevent this cell damage. METHODS: We have investigated the patho-mechanism of secondary epileptogenesis by using the rat model injected with kainic acid (KA) into the unilateral hippocampus. KA model shows initial complex partial seizures originating from the limbic structures and following convulsive status epilepticus. Immunohistochemical staining for c-fos expression, TUNEL stain for apoptosis, and hematoxylin-eosin (H-E) stain for morphologic changes were used. RESULTS: In the injected hippocampus, transient activation of c-fos was expressed in the dentate gyrus and CA3 hippocampal area, which were shaded out within 24 hours after the onset of limbic seizure. The stained cell with normal appearance was not observed in the H-E stain after 72 hours due to diffuse cell death. In the contralateral hippocampus, transient expression of c-fos was observed in the dentate gyrus, hilus, CA3, and CA1 area. But the expression of c-fos in the CA3 and CA1 area was sustained to 24 hours. Cell loss was mild in the CA3 and hilus, and mild cell degeneration and shrinkage were observed in the CA1 area. Apoptotic body was expressed in the CA1 area at 72 hours after the onset of seizure. CONCLUSION: These results mean that the area of prolonged expression of c-fos is vulnerable to apoptosis. Also it suggests that the patho-mechanism of ipsilateral hippocampus is an acute cytotoxic edema, whereas the contralateral damage is an apoptosis.

Electroencephalographic, Behavioral and Pathologic Characteristics in Experimental Complex Partial Seizure Induced by Microinjection of Kainic Acid into the Unilateral Amygdala in the Rat

Kainic acid(KA) is an excitotoxic analogue of glutamate which is now widely used in the studies of epilepsy. Electroencephalographic, behavioral and pathologic observation were done for 2 months after microinjection of kainic acid(Kainic acid group;0.4 microgram, 0.8 microgram, 1.2 microgram, 1.6 microgram, 2.0 microgram, 3.0 microgram) and phosphate buffer solution(Control group) into the left basolateral amygdala(AMG) in 30 Spaque-Doley rats. The control group showed no change in EEG and behavior during the observation period and pathologic findings were normal. One of four rats which 1.2 microgram of KA was injected, four of six rats of 1.6 microgram, all six rats of 2.0 microgram, one of four rats of 3.0 microgram developed acute complex partial seizure and multiple epileptic spikes with high amplitude in EEG. One of four rats of 1.2 microgram, one of six rats of 1.6 microgram, three of six rats of 2.0 microgram, showed spontaneous limbic seizure 14~21days after kainic acid injection. Among those which developed spontaneous limbic seizure, two rats demonstrated spontaneous secondarily generalized seizure 30~60days after kainic acid injection. Pathological examination revealed focal necrosis with perifocal gliosis at the tip of the cannula in the left amygdala. Neuronal cell loss was observed in the CA3 portion of pyramidal cell layer of the hippocampus on the injected side of KA, which developed spontaneous secondarily generalized seizure. But the cellular architecture was normal in the contralateral hippocampus. This is regarded as a good medel of spontaneous generalized complex partial seizure, which is similar to that of temporal lobe epilepsy in human.