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 cou ld be involved in the death process induced by cerebral ischaemia. In order to further clarify their role and examine how the anti-apoptotic protein B cl-2 could influence this process, the time-course of mRNA expression of va rious cell death genes was studied from 1 to 14 days following permanent oc clusion of the middle cerebral artery in wild-type (WT) and Bcl-2 transgeni c mice, within and outside the area of infarction. No differences of the in farct 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 transgen e. Seven days after the ischaemic insult, the mRNA expression of the cell d eath gene effector cpp32 was dramatically upregulated in the penumbra of WT and Bcl-2 transgenic mice. Interestingly, the cpp32 transcript was markedl y 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 n ot transgenic mice. This suggests that cpp32 mRNA may be induced in an atte mpt 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 r esults, the pathophysiological mechanisms that underly neuronal damage foll owing ischaemia need consideration in order to evaluate the extent of neuro protection that may be afforded by the Bcl-2 anti-apoptotic protein. Althou gh the present study does not confirm previous data showing a protective ro le of Bcl-2 in neocortical infarcted areas, it suggests that anti-apoptotic therapies may constitute a possible treatment for areas of the brain remot e from those directly affected by ischaemia.