Effect of lamotrigine treatment on status epilepticus-induced neuronal damage and memory impairment in rat.
Status epilepticus causes neuronal damage that is associated with cognitive impairment. The present study examined whether a novel antiepileptic drug, lamotrigine (LTG), alleviates status epilepticus-induced temporal lobe damage and memory impairment, and compared its efficacy with carbamazepine. Status epilepticus was induced by electric stimulation of the perforant pathway (PP) in rats. Treatment with LTG (12.5 mg/kg, twice a day) was started either 3 days before (preLTG group) or 1 h after (postLTG group) a 60 min PP stimulation. Treatment with carbamazepine (CBZ; 30 mg/kg, twice a day) was started 3 days before (CBZ group) a 60 min PP stimulation. All treatments were continued for 2 weeks. Thereafter, the severity of seizures, seizure-induced neuronal damage, quantitative electroencephalogram (EEG), and memory impairment were compared between vehicle-treated unstimulated and stimulated controls, LTG-treated rats, and CBZ-pretreated rats. Both in the preLTG and postLTG groups, damage to hilar somatostatin-immunoreactive neurons, hippocampal CA3b and CA3a pyramidal cells, and the piriform cortex was mild and did not differ from that in unstimulated controls. Furthermore, CA3c damage in the preLTG group did not differ from that in unstimulated controls. Vehicle-treated stimulated controls and CBZ-pretreated rats, however, had significant damage in the hilus, CA3 subregions, and piriform cortex compared with unstimulated controls (P<0.05 for the stimulated side, contralateral side, or both). Treatment with LTG or CBZ had no effect on the number or duration of behavioral seizures during PP stimulation. They did not affect the baseline EEG or status epilepticus-induced slowing of the EEG. Also, the status epilepticus-induced spatial memory impairment in the Morris water-maze was not attenuated by treatment with LTG or CBZ. Our data demonstrate that treatment with LTG has a mild neuroprotective effect on status epilepticus-induced neuronal damage in rats even when administered after the beginning of status epilepticus.
Halonen
T
T
A.I. Virtanen Institute for Molecular Sciences, Epilepsy Research Laboratory, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland.
Nissinen
J
J
Pitkänen
A
A
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D000077213:Lamotrigine; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000188:drug therapy* / Q000473:pathology*; D014227:Triazines / Q000494:pharmacology* / Q000627:therapeutic use
D000927:Anticonvulsants; D018696:Neuroprotective Agents; D014227:Triazines; D000077213:Lamotrigine