Genetic control of sensitivity to hippocampal cell death induced by kainic acid: a quantitative trait loci analysis.

Host genetic factors are likely to contribute to differences in individual susceptibility to seizure-induced excitotoxic neuronal damage. Similarly, inbred strains of mice differ in their susceptibility to the kainic acid (KA) model of seizure-induced cell death, but the genes responsible for the differences are not known. Here, we define the inheritance patterns of susceptibility to KA-induced neurodegeneration in the hippocampus by assessing 331 back-cross (N2) progeny of two inbred mouse strains, C57BL/6 and FVB/N, previously shown to display resistance and sensitivity to KA-induced cell death, respectively.

Protection provided by cyclosporin A against excitotoxic neuronal death is genotype dependent.

Purpose: Previous studies have shown that the immunosuppressant cyclosporin A (CsA), a specific blocker of the mitochondrial permeability transition (MPT) pore, can dramatically ameliorate the selective neuronal necrosis resulting from ischemia-reperfusion, traumatic brain injury, and N-methyl-d-aspartate (NMDA)-evoked neurotoxicity. The purpose of this study was to determine whether two different immunosuppressants, CsA and FK-506, could ameliorate the neuronal damage observed after kainate-induced seizures in strains that are differentially susceptible to excitotoxin-induced cell death.

Methods: Excitotoxin-resistant (C57BL/6) or -susceptible (FVB/N) mice were administered kainate alone (30 mg/kg), CsA alone (5, 10, or 20 mg/kg), or one of the immunosuppressants (CsA, 5 mg/kg or 10 mg/kg; FK-506, 0.