Amelioration of cerebral vasospasm and secondary injury by Vigabatrin following experimental subarachnoid hemorrhage in the rabbit

Objective: Vigabatrin, an antiepileptic drug, increases the level of gamma aminobutyric acid in the brain via inhibiting its catabolism. As gamma aminobutyric acid has been proved to have vasodilatory effect, in the present study, we aimed to investigate the effect of Vigabatrin, in experimental subarachnoid hemorrhage (SAH) induced vasospasm.

Material and methods: Three groups of New Zealand white rabbits with a total number of 30 were divided as the control group, the SAH group, and the Vigabatrin group (n=10, in each group). Experimental SAH was established by the injection of autologous arterial blood into the cisterna magna. In the Vigabatrin group, the subjects were administered Vigabatrin for three days after the SAH. First dose of Vigabatrin is given two hours after SAH. A daily dose of 500 mg/kg Vigabatrin was administered intraperitoneally. After three days the animals were sacrificed and the brains were removed together with the cerebellum and brainstem. Basilar artery wall thicknesses and lumen areas were measured. The neuronal degeneration in the hippocampus (CA1, CA3, and dentate gyrus) were also evaluated.

Results: The arterial wall thickness of the Vigabatrin group was less than the SAH group (p<0.001) and the mean luminal area of the Vigabatrin group was greater than the SAH group (p<0.001). Additionally, the hippocampal neuronal degeneration score of the Vigabatrin group was lower than the SAH group (p<0.001).

Conclusion: These findings indicated that Vigabatrin has a vasodilatory effect in an experimental SAH model in the rabbit. Moreover it has a neuroprotective effect in the hippocampal neurons against secondary injury induced by SAH.