Tin chloride enhances parvalbumin-positive interneuron survival by modulating heme metabolism in a model of cerebral ischemia.

SnCl2 has been reported to increase the expression of heme-oxygenase 1 (HO-1), a major antioxidant enzyme, and to decrease ischemic injury, in non-nervous tissues. This study examined the neuroprotective effect of SnCl2 in the hippocampus of rats submitted to cerebral ischemia. SnCl2 wasadministered 18 h before bilateral carotids obstruction. Changes in HO-1 expression and activity, heme content, inducible nitric oxide synthase (iNOS) expression and parvalbumin positive interneuron survival were studied. Thereafter both behavior and memory recovery were tested. The administration of SnCl2 increased the expression of HO-1 protein and HO activity in the hippocampus and concomitantly decreased heme content at both mitochondrial and nuclear level. Furthermore, ischemized animals showed a strong increase in iNOS expression in the hippocampus, where a loss of parvalbumin positive interneurons also occurred. Pre-treatment with SnCl2, decreased both iNOS expression in ischemized rats and increased cell survival. The beneficial effects of SnCl2 were prevented by concomitant treatment with SnMP, a strong inhibitor of HO activity. SnCl2 also caused an improvement in short term memory recovery. Our results showed that following SnCl2 administration, HO-1 is strongly induced in the hippocampus and modulate iNOS expression, resulting in a strong neuroprotective effect.