BACKGROUND & OBJECTIVES: MNDA antagonists such as ketamine and MK-801 in experimental status epilepticus model were reported to have the effect of neuroprotection. It may be postulated that one of the mechanisms of neuronal damage is a calcium influx related to excitatory neurotransmmition. So we investigated the effects of various voltage gated calcium channel blockers on epileptogenic and neuroprotection in the hippocampus of lithium-pilocarpine induced status epilepticus animal mode]. Methods ; Each Sprague-Dawley rat (N=47) was injected intraperitoneally with lithium 3mEq/kg and pilocarpine 30 mg/kg to produce the satus epilepticus. The effects of pre-(15 minute before the injection of pilocarpine) and post-administration(15 minutes after the onset of seizure) of various voltage gated calcium channel (VGCC) blockers[nimodipine (NMDP), flunarizine (FRZ), verapamil(VPM), and diltiazem(DTZ) -20mg/kg I.p.] were tested by conting survived neurons on the hippocampus in lithim-pilocarpine induced status epilepticus rat model. RESULTS: Pre- & post- administration of each VGCC blocker protected the neurola damage in CA1 and CA3 area of the hippocampus (CA1 6.0+1.87 and CA3 2.6+0.89 in seizure control group, 43.2+/-4,32, and 28.0+4.47 in the NMDP, 44.8+/-7.46 and 29.0+4.30 in post-NMDP, 43.0+0.74 and 29.6+4.78 in pre-FRZ, 45.4+/-6.88 and 23.6+/-5.68 in post-FRZ, 37.2+/-5.85 and 18.4+5.68 in pre-VPM, 38.8+4.92 and 16.6+4.39 in post-VPM, 38.8+6.14 and 17.2+3.70 in pre-DTZ, and 39.6+8.26 and 15.6+5.41 in post-DTZ). The latencies from pilocarpine injection to the seizure onset behavioral alteration ictal electroencephalographic discharges during status epileptics were not changed despite pre- and post-adminstration of each VGCC blocker. These result indicate that VGCC blockers do not have a direct effect on epileptogenesis but have some relationship with neuroprotection. CONCLUSION: It was concluded that the neuroprotecting effect of VGCC blocker in the neuronal damage due to status epileptics appears to be produced by blocking the intracellular calcium influx through the VGCC, blochers might be helpful to reduce neuronal damage in human with status epilepticus.
Animals ; Calcium Channel Blockers* ; Calcium Channels* ; Calcium* ; Dizocilpine Maleate ; Flunarizine ; Hippocampus* ; Humans ; Ketamine ; Lithium ; Models, Animal* ; Neurons ; Pilocarpine ; Rats* ; Rats, Sprague-Dawley ; Seizures ; Status Epilepticus*

BACKGROUND & OBJECTIVES: MNDA antagonists such as ketamine and MK-801 in experimental status epilepticus model were reported to have the effect of neuroprotection. It may be postulated that one of the mechanisms of neuronal damage is a calcium influx related to excitatory neurotransmmition. So we investigated the effects of various voltage gated calcium channel blockers on epileptogenic and neuroprotection in the hippocampus of lithium-pilocarpine induced status epilepticus animal mode]. Methods ; Each Sprague-Dawley rat (N=47) was injected intraperitoneally with lithium 3mEq/kg and pilocarpine 30 mg/kg to produce the satus epilepticus. The effects of pre-(15 minute before the injection of pilocarpine) and post-administration(15 minutes after the onset of seizure) of various voltage gated calcium channel (VGCC) blockers[nimodipine (NMDP), flunarizine (FRZ), verapamil(VPM), and diltiazem(DTZ) -20mg/kg I.p.] were tested by conting survived neurons on the hippocampus in lithim-pilocarpine induced status epilepticus rat model. RESULTS: Pre- & post- administration of each VGCC blocker protected the neurola damage in CA1 and CA3 area of the hippocampus (CA1 6.0+1.87 and CA3 2.6+0.89 in seizure control group, 43.2+/-4,32, and 28.0+4.47 in the NMDP, 44.8+/-7.46 and 29.0+4.30 in post-NMDP, 43.0+0.74 and 29.6+4.78 in pre-FRZ, 45.4+/-6.88 and 23.6+/-5.68 in post-FRZ, 37.2+/-5.85 and 18.4+5.68 in pre-VPM, 38.8+4.92 and 16.6+4.39 in post-VPM, 38.8+6.14 and 17.2+3.70 in pre-DTZ, and 39.6+8.26 and 15.6+5.41 in post-DTZ). The latencies from pilocarpine injection to the seizure onset behavioral alteration ictal electroencephalographic discharges during status epileptics were not changed despite pre- and post-adminstration of each VGCC blocker. These result indicate that VGCC blockers do not have a direct effect on epileptogenesis but have some relationship with neuroprotection. CONCLUSION: It was concluded that the neuroprotecting effect of VGCC blocker in the neuronal damage due to status epileptics appears to be produced by blocking the intracellular calcium influx through the VGCC, blochers might be helpful to reduce neuronal damage in human with status epilepticus.
Animals ; Calcium Channel Blockers* ; Calcium Channels* ; Calcium* ; Dizocilpine Maleate ; Flunarizine ; Hippocampus* ; Humans ; Ketamine ; Lithium ; Models, Animal* ; Neurons ; Pilocarpine ; Rats* ; Rats, Sprague-Dawley ; Seizures ; Status Epilepticus*