NEUROPROTECTIVE EFFECTS OF LAMOTRIGINE IN GLOBAL-ISCHEMIA IN GERBILS - A HISTOLOGICAL, IN-VIVO MICRODIALYSIS AND BEHAVIORAL-STUDY

A sudden surge in the release of glutamate is currently believed to be an important initiating step in neuronal damage due to an ischemic in sult. In this experiment, we tested the efficacy of neuroprotection wi th lamotrigine, a novel antiepileptic drug that blocks voltage gated s odium channels and inhibits the ischemia-induced release of glutamate in the gerbil forebrain model of cerebral ischemia. The medication was administered 30 min before and 30 min after the insult in two groups of animals. Histological assessment of neuronal damage was evaluated a t 7 and 28 days after the ischemic insult. Animals evaluated at 28 day s also underwent behavioral testing. Microdialysis was used in the sam e model to study the response of ischemia-induced glutamate in saline treated controls versus animals treated with lamotrigine 20 min before the insult. There was highly significant neuronal protection in anima ls who were treated with lamotrigine either before or after the insult . Protection was seen both at 7 and 28 days after the insult. Behavior al testing also showed significantly better recovery in both sets of a nimals in comparison to the saline-treated group. Microdialysis confir med a significant attenuation of the ischemia-induced glutamate surge when compared to the saline-treated animals. Our morphological, behavi oral and microdialysis experiments show that lamotrigine offers signif icant neuroprotection from the effects of transient forebrain ischemia in gerbils. Neuroprotection with post-ischemic therapy probably depen ds on preserving the capacity of the sodium/calcium exchanger to reduc e intracellular calcium concentrations or persistent 'toxicity' of glu tamate in the reperfusion period on the already 'primed' injured neuro ns. These concepts need further study.