PMID- 11518623
DA - 20010823
DCOM- 20011204
IS - 0920-1211
VI - 46
IP - 3
DP - 2001 Sep
TI - Effect of lamotrigine treatment on status epilepticus-induced neuronal damage and memory impairment in rat.
PG - 205-23 AB - 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.
AD - A.I. Virtanen Institute for Molecular Sciences, Epilepsy Research
Laboratory, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio,
Finland.
FAU - Halonen, T
AU - Halonen T
FAU - Nissinen, J
AU - Nissinen J
FAU - Pitkanen, A
AU - Pitkanen A
LA - eng
PT - Journal Article
CY - Netherlands
TA - Epilepsy Res
JID - 8703089
RN - 0 (Anticonvulsants)
RN - 0 (Neuroprotective Agents)
RN - 0 (Triazines)
RN - 84057-84-1 (lamotrigine)
SB - IM
MH - Animal
MH - Anticonvulsants/*pharmacology/therapeutic use
MH - Body Temperature/drug effects
MH - Body Weight/drug effects
MH - Brain/drug effects/pathology
MH - Comparative Study
MH - Male
MH - Memory Disorders/*drug therapy
MH - Neurons/drug effects/*pathology
MH - Neuroprotective Agents/pharmacology/therapeutic use
MH - Rats
MH - Rats, Wistar
MH - Status Epilepticus/*drug therapy/*pathology
MH - Support, Non-U.S. Gov't
MH - Triazines/*pharmacology/therapeutic use
EDAT- 2001/08/24 10:00
MHDA- 2002/01/05 10:01
AID - S0920121101002789 [pii]
PST - ppublish
SO - Epilepsy Res 2001 Sep;46(3):205-23.