J Korean Child Neurol Soc.  2001 May;9(1):25-35.

The Effect of MK 801 on the Development of Brain Damage, Spontaneous Recurrent Seizures and Mossy Fiber Sprouting in the Pilocarpine Induced Status Epilepticus Animal Model

• Whoang GE
• An RZ
• Lim HH
• Lee KS

Abstract

PURPOSE: We investigated the effect on MK 801 on the development on brain damage, spontaneous recurrent seizures and mossy fiber sprouting in the pilocarpine induced status epilepticus animal model. Methods: Fifty two adult Sprague Dawley male rats(180-240gm) were studied under ketamine/xylazine(87mg/13mg/kg, IP) anesthesia and were implanted at the F3, P3, F4, P4 areas for recording EEG. With a single intraperitoneal(IP) administration of pilocarpine hydrochloride(360mg/kg), 70% developed status epilepticus(SE). When SE was not induced within 1 hour after injection of pilocarpine, the second dose of pilocarpine(175mg/kg, IP) was injected, with 86.6% of success. Results: All studied animals were divided into two large groups, one group was treated with NMDA receptor antagonist, the other was control group. The mean duration of SE was 62.00+/-6.80 minutes in the MK 801(1mg/kg, IP, 30 minutes after SE) treated group, and 61.10+/-7.37 minutes in the control group without any signigicant differences(P>0.05). Neuronal loss(necrosis dominantly) was observed at CA1 and CA3 areas in the control group, with more loss after 6 weeks than 24 or 72 hrs specimens. However, there was no neuronal loss in MK 801 treated group. The protective effect of MK 801 for neuronal injury suggested the glutamate receptor activation was involved in the neuronal injury induced by repeated seizure attack. Spontaneous recurrent seizures(SRS) were observed 70% of animals in the control group, but there were no SRS observed in the MK 801 treated group. The mean scores of mossy fiber sprouting were significantly higher in the control group(2.05+/-0.47) than MK 801 treated group(0.4+/-0.32)(P<0.05). Conclusion: These results suggested that SRS and mossy fiber sprouting were associated with NMDA receptor activation, and NMDA receptor activation had a key role in the epilepsy development.

Keyword

Pilocarpine; Status epilepticus; MK 801; Mossy fiber sprouting

MeSH Terms

Adult
Anesthesia
Animals*
Brain*
Dizocilpine Maleate*
Electroencephalography
Epilepsy
Humans
Male
Models, Animal*
N-Methylaspartate
Neurons
Pilocarpine*
Receptors, Glutamate
Seizures*
Status Epilepticus*
Dizocilpine Maleate
N-Methylaspartate
Pilocarpine
Receptors, Glutamate