Neuron-specific transgene expression of Bcl-X-L but not Bcl-2 genes reduced lesion size after permanent middle cerebral artery occlusion in mice

Protective effects after focal cerebral ischemia were assessed in transgeni c mice that overexpress in a neuron-specific fashion mouse Bcl-X-L or human Bcl-2. Both Eel genes were under the control of the same mouse Thy-1 regul atory sequences resulting in very similar expression patterns in cortical n eurons. Furthermore, these sequences direct late-onset (i.e. around birth) expression in brain, thus minimizing effects of transgene expression during brain development. Effects on infarct volume were measured using MRI after permanent occlusion of the middle cerebral artery (MCA). When compared to their non-transgenic littermates, Thy1mbcl-X-L mice showed a significant 21 % reduction in infarct size whereas Thy1hbcl-2 mice did not reveal any redu ction. These findings suggest a selective protective advantage of Bcl-XL as compared with Bcl-2 in this mouse model for human stroke. (C) 1999 Elsevie r Science Ireland Ltd. All rights reserved.