Effects of nimodipine on the behavioral sequalae of experimental status epilepticus in prepubescent rats.
OBJECTIVE
The goal of this study was to investigate the potential protective effects of nimodipine (ND), a calcium channel blocker, on the acute manifestations and long-term behavioral sequalae of experimental status epilepticus (SE).


METHODS
Three groups of Postnatal Day (P) 35 rats undergoing kainic acid (KA)-induced SE were injected with phenobarbital (PB) and/or ND, and were subsequently compared with rats injected with KA alone and normal control rats. Behavioral parameters were assessed by the Morris water maze, open field, and handling tests at P125-P135. Acute seizures and spontaneous recurrent seizures (SRS) were assessed by videotape techniques.


RESULTS
PB reduced the severity of SE acutely, and protected completely against subsequent long-term SRS, memory impairment, and hyperactivity, and partially against aggressivity. ND alone had no effect on acute seizure activity, but did protect against subsequent SRS and memory impairment, and partially against aggressivity. When administered together, PB and ND had effects similar to those seen with PB alone. However, in addition, and unlike the PB- and ND-alone groups, the PB-ND group was completely protected against KA-induced increased aggressivity.


CONCLUSIONS
Activation of L-type calcium channels contributes to the long-term behavioral sequalae of KA-induced SE, but is not essential for the development and maintenance of SE. ND has protective effects in SE when given alone or in conjunction with a traditional antiepileptic drug. Calcium channel blockers should be further investigated as add-on protective agents in models of SE and possibly in clinical trials.
Mikati
Mohamad A
MA
Department of Pediatrics, and Adult and Pediatric Epilepsy Program, Faculty of Medicine, American University of Beirut, Lebanon. mamikati@aub.edu.lb
Holmes
Gregory L
GL
Werner
Suzanne
S
Bakkar
Nadine
N
Carmant
Lionel
L
Liu
Zhao
Z
Stafstrom
Carl E
CE
D000374:Aggression / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005260:Female; D007274:Injections, Intraperitoneal; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009553:Nimodipine / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology; D011292:Premedication; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000523:psychology*
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D009553:Nimodipine; D010634:Phenobarbital