The proapoptotic BCL-2 homology domain 3-only protein Bim is not critical for acute excitotoxic cell death.

Prolonged and repetitive epileptic activity is causally linked to neuronal cell death in the brain and is most marked in vulnerable subfields of the hippocampus. The Bcl-2 family protein Bim, a proapoptotic member of the BCL-2 homology domain 3-only subfamily, has been implicated as an important mediator of neuronal cell damage in various pathological conditions, although its role in epilepsy-associated cell death is not understood. We performed intrahippocampal stereotaxic injections of the glutamate analog kainic acid as an in vivo model of acute excitotoxicity to assess neuronal injury in Bim-deficient and control wild-type mice. A variety of cell death parameters including chromatin condensation, TdT-mediated dUTP nick end labeling, and caspase-3 activity was assessed. We found no differences in the extent of hippocampal neuronal death parameters between the 2 groups. Moreover, electroencephalographic recordings after kainic acid injection revealed indistinguishable patterns of seizure activity in Bim-deficient and wild-type animals. These in vivo and histological data suggest that Bim is not critically involved in excitotoxicity-induced acute neuronal cell injury.