Bim notes in the neuronal executioner's song

April 02, 2004

Brain damage often results after prolonged seizures as well as after brief or repetitive epileptic seizures. Previous work has indicated that loss of neurons in the hippocampus after seizures may be due to onset of programmed cell death. Members of the Bcl-2 family are known to activate a pathway ending in the release of several caspases, including the 'executioner,' caspase-3. David Henshall and colleagues, of Robert S. Dow Neurobiology Laboratories, investigate molecular members of the programmed cell death pathway and show that reduction of Bim (Bcl-2-interacting mediator of cell death) may provide protection from neuronal loss. The researchers examined Bim expression in both experimentally induced seizures in rats and in patients with temporal lobe epilepsy. In instances of experimentally-produced prolonged seizures that damaged the hippocampus in rats, Bim expression increased. Blocking upstream activators of Bim or using Bim antisense to block Bim expression reduced neuronal damage. Of interest, in the hippocampus of epileptic patients, Bim appeared to be selectively down-regulated. These results suggest a means by which the brain may protect itself from additional neural damage following epileptic seizures. Targeting this molecular pathway may be worthwhile for ameliorating seizure-induced brain injuries.

An accompanying commentary by Jerome Niquet and Claude Wasterlain, of Epilepsy Research Laboratory, place this work in context with the complexity of cell-death pathways and highlight specific areas of future analysis that are still required to understand the molecular mechanisms at play in neuronal damage.
TITLE: Bim regulation may determine hippocampal vulnerability after injurious seizures and in temporal lobe epilepsy

David C. Henshall
Robert S. Dow Neurobiology Laboratories, Portland, Oregan, USA.
Phone: 503-413-5260
Fax: 503-413-5465

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ACCOMPANYING COMMENTARY: Bim, Bad, and Bax: a deadly combination in epileptic seizures

Jerome Niquet
Epilepsy Research Laboratory, West Los Angeles, California, USA.
Phone: 310-478-3711 ext. 41974
Fax: 310-268-4856

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