Targeted disruption of the bcl-2 gene in mice exacerbates focal ischemic brain injury.
Neuronal death after brain ischemia is mainly due to necrosis but there is also evidence for involvement of apoptosis. To test the importance of apoptosis, we investigated the effect of targeted disruption of the apoptosis-suppressive gene bcl-2 on the severity of ischemic brain injury. Transient focal ischemia for 1 hour was induced by occlusion of the middle cerebral artery in homozygous (n=7) and heterozygous (n=6) bcl-2 knockout mice as well as in their wildtype littermates (n=5). Bcl-2 ablation did not influence cerebral blood flow but it significantly increased infarct size and neurological deficit score at 1 day after reperfusion in a gene-dose dependent manner. The exacerbation of tissue damage in the absence of Bcl-2 underscores the importance of apoptotic pathways for the manifestation of ischemic injury after transient vascular occlusion.
Hata
R
R
Department of Experimental Neurology, Max-Planck-Institute for Neurological Research, Cologne, Germany.
Gillardon
F
F
Michaelidis
T M
TM
Hossmann
K A
KA
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000150:complications / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000098:blood supply; D002544:Cerebral Infarction / Q000473:pathology; D002560:Cerebrovascular Circulation; D005260:Female; D019254:Genes, bcl-2; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics* / Q000502:physiology*; D009422:Nervous System Diseases / Q000209:etiology