Cell death is prevented in thalamic fields but not in injured neocortical areas after permanent focal ischaemia in mice overexpressing the anti-apoptotic protein Bcl-2.

Previous studies have suggested that various apoptotic-related proteins could be involved in the death process induced by cerebral ischaemia. In order to further clarify their role and examine how the anti-apoptotic protein Bcl-2 could influence this process, the time-course of mRNA expression of various cell death genes was studied from 1 to 14 days following permanent occlusion of the middle cerebral artery in wild-type (WT) and Bcl-2 transgenic mice, within and outside the area of infarction. No differences of the infarct sizes were observed between the two groups of mice, showing that the extent of neuronal injury could not have been lowered by the Bcl-2 transgene. Seven days after the ischaemic insult, the mRNA expression of the cell death gene effector cpp32 was dramatically upregulated in the penumbra of WT and Bcl-2 transgenic mice. Interestingly, the cpp32 transcript was markedly induced from 3 days in the ipsilateral thalamus of the two groups of mice. However, apoptotic bodies were observed in the thalamic field of WT but not transgenic mice. This suggests that cpp32 mRNA may be induced in an attempt to kill the injured cells and, in contrast to the penumbra, cell death in the thalamus may be prevented in Bcl-2 transgenic mice. Based on these results, the pathophysiological mechanisms that underly neuronal damage following ischaemia need consideration in order to evaluate the extent of neuroprotection that may be afforded by the Bcl-2 anti-apoptotic protein. Although the present study does not confirm previous data showing a protective role of Bcl-2 in neocortical infarcted areas, it suggests that anti-apoptotic therapies may constitute a possible treatment for areas of the brain remote from those directly affected by ischaemia.