Blockade of the Subthalamo-nigral Pathway Prevents the Motor Component of Pilocarpine Induced Generalized Convulsive Seizure in Rats

J Korean Neurol Assoc > Volume 18(2); 2000 > Article

Journal of the Korean Neurological Association 2000;18(2): 192-198.

시상하핵-흑질망상부 신경로 차단이 필로카르핀으로 유도된 경련에 미치는 영향

최재영, 김혜식이김영인이박성민이이광수이김범생

가톨릭대학교 의과대학 신경과학교실

Blockade of the Subthalamo-nigral Pathway Prevents the Motor Component of Pilocarpine Induced Generalized Convulsive Seizure in Rats

Jae-Young Choi, M.D., Hye-Sik Kim, M.D., Yeong-In Kim, M.D., Seong-Min Park, M.D., Kwang-Soo Lee, M.D., Beum-Saeng Kim, M.D.

Department of Neurology, Catholic University Medical College

Abstract

B a c k g r o u d : The substantia nigra pars reticulata is a critical site for the control of epileptic seizures. The potentiation of the inhibitory gamma - amino butyric acid (GABA) ergic input from the striatum to the substantia nigra pars reticulata suppresses primary or secondary generalized seizures in rats. Recent data suggests that the projection from the subthala-mus to the substantia nigra pars reticulata plays a critical role in the control of some forms of epileptic seizures. M e t h o d s : We examined the possible involvement of the excitatory glutamatergic input from the subthalamic nucleus (STN) to the substantia nigra in pilocarpine-induced seizures by the direct injection of GABA receptor agonist (muscimol) and n-methyl- D-aspartate (NMDA) receptor antagonist (MK-801) into the substantia nigra pars reticularis (SNr) and the sub-thalamic nucleus respectively. Sprague-Dawley rats were classified into four groups depending on the pretreatment; the injection of saline (STN sham) or muscimol (STN) into the subthalamic nucleus, and the injection of saline (SNr sham) or MK-801 (SNr) into the substantia nigra. Seizure was induced by the intraperitoneal injection of pilocarpine (400 mg/kg). R e s u l t s : Mean seizure stages in the STN group (1.5 ±0.5) and SNr group (1.3 ±0.5) were significantly lower than STN sham group (4.8 ±0.4) and SNr sham group (4.8 ±0.4) (P 〈0.05). Electroencephlograms showed typical status epilepticus patterns in the sham operation group but only discrete ictal discharges with slowing and intermittent ictal spikes were shown in both STN and SNr group. Viable cell numbers in the CA1 and CA3 in STN and SNr groups were significantly higher than those of the sham group (P 〈0.05). C o n c l u s I o n s : These results provide evidence for the role of subthalamo-nigral projections in the modulation of pilocarpine-induced seizures. J Korean Neurol Assoc 18(2):192~198, 2000 Key Words : Subthalamus, Substantia nigra, Seizure, Muscimol, MK-801, Pilocarpine Manuscript received October 13,1999. Accepted in final form November 23,1999.