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. 1997 Mar 15;99(6):1453–1459. doi: 10.1172/JCI119304

Transient cerebral ischemia. Association of apoptosis induction with hypoperfusion.

Z S Vexler 1, T P Roberts 1, A W Bollen 1, N Derugin 1, A I Arieff 1
PMCID: PMC507961  PMID: 9077555

Abstract

Apoptosis is thought to be important in the pathogenesis of cerebral ischemia. The mechanism of apoptosis induction remains unclear but several studies suggest that it is preferentially triggered by mild/moderate microcirculatory disturbances. We examined in cats whether induction of apoptosis after 2.5 h of unilateral middle cerebral artery occlusion plus 10 h of reperfusion is influenced by the degree of cerebral microcirculatory disturbance. Quantitative monitoring over time of the disturbances of cerebral microcirculation in ischemic brain areas and evaluation of cytotoxic edema associated with perfusion deficits was achieved by using two noninvasive magnetic resonance imaging techniques: (a) high-speed echo planar imaging combined with a bolus of magnetic susceptibility contrast agent; and (b) diffusion-weighted imaging. Apoptosis-positive cells were counted in anatomic areas with different severity of ischemic injury characterized by magnetic resonance imaging, triphenyltetrazolium chloride, and hemotoxylin and eosin staining. The number of apoptosis-positive cells was significantly higher in anatomic areas with severe perfusion deficits during occlusion and detectable histologic changes 10 h after reperfusion. In contrast, in areas where perfusion was reduced but maintained during occlusion there were no detectable histological changes and significantly fewer apoptosis-positive cells. A similar number of cells that undergo apoptosis were shown in regions with transient or prolonged subtotal perfusion deficits. These results suggest that the apoptotic process is induced in the ischemic core and contributes significantly in the degeneration of neurons associated with transient ischemia.

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Selected References

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