Anticonvulsant lamotrigine administered on reperfusion fails to improve experimental stroke outcomes.
OBJECTIVE
Recent results suggest that selective inhibitors of presynaptic neuronal ion channels can diminish glutamate release during cerebral ischemia and modulate excitotoxic cell death. The aim of the present study was to evaluate lamotrigine (LTG), an antiepileptic that inhibits presynaptic sodium and voltage-sensitive calcium channels, as a potential stroke resuscitation agent in the rat. Three dosages of LTG were examined for effect on infarction volume and sensorimotor behavioral recovery after middle cerebral artery (MCA) occlusion.


METHODS
Halothane-anesthetized male Wistar rats were subjected to 2 hours of MCA occlusion by the intraluminal occlusion technique. Physiological variables were controlled, and ipsilateral cortical perfusion was monitored by laser Doppler flowmetry throughout ischemia. At onset of reperfusion, rats received intravenous LTG 5, 10, or 20 mg/kg or PBS (n=9 to 11 per group) during 15 minutes. Behavioral assessment was completed at 3 and 7 days after stroke, and the brain was harvested for histology (triphenyltetrazolium chloride staining).


RESULTS
Values are mean+/-SE. Cortical infarction volumes were unchanged in LTG-treated animals: 14+/-6% of contralateral cortex at 5 mg/kg LTG, 17+/-7% at 10 mg/kg, and 30+/-6% at 20 mg/kg, versus saline-treated cohorts (12+/-3%; P:=0.19; n=9). Caudate-putamen infarction injury was also unchanged (37+/-11% of contralateral caudate-putamen at 5 mg/kg LTG, 44+/-8% at 10 mg/kg, and 65+/-9% at 20 mg/kg versus saline (38+/-11%; P:=0.18). Total infarction was not different among groups (P:=0.15). Consistent with histology, behavioral outcomes were unimproved by treatment.


CONCLUSIONS
Histological damage and behavioral recovery at 7 days after MCA occlusion was not altered by LTG treatment over the dosage range used in the present study.
Traystman
R J
RJ
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21287, USA. rtraystm@jhmi.edu
Klaus
J A
JA
DeVries
A C
AC
Shaivitz
A B
AB
Hurn
P D
PD
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy*; D000077213:Lamotrigine; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects; D015424:Reperfusion; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology; D017211:Treatment Failure; D014227:Triazines / Q000008:administration & dosage*
D000927:Anticonvulsants; D014227:Triazines; D000077213:Lamotrigine