TRANSIENT CEREBRAL-ISCHEMIA - ASSOCIATION OF APOPTOSIS INDUCTION WITHHYPOPERFUSION

Apoptosis is thought to be important in the pathogenesis of cerebral i schemia. The mechanism of apoptosis induction remains unclear but seve ral studies suggest that it is preferentially triggered by mild/modera te microcirculatory disturbances. We examined in cats whether inductio n of apoptosis after 2.5 h of unilateral middle cerebral artery occlus ion plus 10 h of reperfusion is influenced by the degree of cerebral m icrocirculatory 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 a chieved 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. Ap optosis-positive cells were counted in anatomic areas with different s everity of ischemic injury characterized by magnetic resonance imaging , triphenyltetrazolium chloride, and hemotoxylin and eosin staining. T he number of apoptosis-positive cells was significantly higher in anat omic areas with severe perfusion deficits during occlusion and detecta ble histologic changes 10 h after reperfusion. In contrast, in areas w here perfusion was reduced but maintained during occlusion there were no detectable histological changes and significantly fewer apoptosis-p ositive cells. A similar number of cells that undergo apoptosis were s hown in regions with transient or prolonged subtotal perfusion deficit s. These results suggest that the apoptotic process is induced in the ischemic core and contributes significantly in the degeneration of neu rons associated with transient ischemia.