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 apopt osis, we investigated the effect of targeted disruption of the apoptosis-su ppressive gene bcl-2 on the severity of ischemic brain injury. Transient fo cal ischemia for 1 hour was induced by occlusion of the middle cerebral art ery in homozygous (n = 7) and heterozygous (n = 6) bcl-2 knockout mice as w ell as in their wildtype littermates (n = 5). Bcl-2 ablation did not influe nce cerebral blood flow but it significantly increased infarct size and neu rological deficit score at 1 day after reperfusion in a gene-dose dependent manner. The exacerbation of tissue damage in the absence of Bcl-2 undersco res the importance of apoptotic pathways for the manifestation of ischemic injury after transient vascular occlusion.