Secondary reduction in the apparent diffusion coefficient of water, increase in cerebral blood volume, and delayed neuronal death after middle cerebral artery occlusion and early reperfusion in the rat

It has been reported recently that very delayed damage can occur as a resul t of focal cerebral ischemia induced by vascular occlusion of short duratio n. With use of diffusion-, T2-, and contrast-enhanced dynamic magnetic reso nance im aging (MRI) techniques, the occlusion time dependence together wit h the temporal profile for this delayed response in a rat model of transien t focal cortical ischemia have been established. The distal branch of the m iddle cerebral artery was occluded for 20, 30, 45, or 90 minutes. Twenty mi nutes of vascular occlusion with reperfusion exhibited no significant mean change in either the apparent diffusion coefficient of water (ADC) or the T 2 relaxation time at 6, 24, 48, or 72 hours after reperfusion (P = 0.97 and 0.70, respectively). Ninety minutes of ischemia caused dramatic tissue inj ury at 6 hours, as indicated by an increase in T2 relaxation times to 135% of the contralateral values (P < 0.01). However, at intermediate periods of ischemia (30 to 45 minutes), complete reversal of the ADC was seen at 6 ho urs after reperfusion but was followed by a secondary decline over time, su ch that a 25% reduction in tissue ADC was seen at 24 as compared with 6 hou rs (P < 0.02). This secondary response was accompanied by an increase in ce rebral blood volume (CBV), as shown by contrast-enhanced dynamic MRI (120% of contralateral values; P < 0.001), an increase in T2 relaxation time (132 %; P < 0.01), together with clear morphological signs of cell death. By day 18, the mean volume of missing cortical tissue measured with high-resoluti on MRI in animals occluded for 30 and 45 minutes was 50% smaller than that in 90-minute occluded animals (P < 0.005). These data show that ultimate in farct size is reduced after early reperfusion and is occlusion time depende nt. The early tissue recovery that is seen with intermediate occlusion rime s can be followed by cell death, which has a delayed onset and is accompani ed by an increase in CBV.