Lamotrigine Protects Hippocampal CA1 Neurons From Ischemic Damage After Cardiac Arrest

Background and Purpose Lamotrigine (LTG) is an anticonvulsant drug whose mechanism of action may involve the inhibition of glutamate release by blocking voltage-dependent sodium channels. Glutamate neurotoxicity may contribute to cerebral ischemic damage after recovery from cardiac arrest. Thus, LTG may prevent the brain damage associated with global cerebral ischemia by reducing the release of glutamate from presynaptic vesicles during the ischemic insult or the early recovery period. Methods LTG was studied in cardiac arrest–induced global cerebral ischemia with reperfusion in rats. In the first set of experiments, LTG (100 mg/kg, PO) was administered before induction of ischemia; and in the second experiment, LTG (10 mg/kg, IV) was given 15 minutes after ischemia and a second dose (10 mg/kg,IV) was given 5 hours later. Results In both experiments LTG reduced the damage to the hippocampal CA1 cell population by greater than 50%. Neuroprotection was not associated with changes in brain temperature or pla...