Regional variations in the apparent diffusion coefficient and the intracellular distribution of water in rat brain during acute focal ischemia

Background and Purpose-The apparent diffusion coefficient of water (ADC) ra pidly drops in ischemic tissue after cerebral artery occlusion. This acute drop is thought to be caused by the loss of extracellular fluid and the gai n of intracellular fluid. To test the latter possibility, changes in ADC an d the size of several cellular compartments were assessed in 3 regions of r at brain at the end of 90 minutes of focal cerebral ischemia. Methods-One middle cerebral artery was permanently occluded in 8 Sprague-Da wley rats; sham occlusions were performed in 2 other rats. ADC maps were ge nerated 90 minutes later, and the brains were immediately perfusion fixed. Three regions of interest (ROIs) were defined on the basis of ADC range. Va rious neuronal, astrocytic, and capillary compartments in each ROI were qua ntified with light and electron microscopy. Results-At the end of 90 minutes of ischemia, mean ADC was normal in the co rtex of sham-operated rats and the contralateral cortex of ischemic rats (R OI-a), 25% lower in the ipsilateral frontoparietal cortex (ROI-b), and 45% lower in the ischemic lateral caudoputamen (ROI-c). At this time, the frequ ency of swollen astrocytic cell bodies and volume of swollen dendrites and astrocytic processes in neuropil were ROI-a < ROI-b < ROI-c. In ROI-b and R OI-c, 40% and 60% of the neurons, respectively, were shrunken; the shrunken neurons were approximate to 25% smaller in ROI-c than in ROI-b. In these a reas, many capillary endothelial cells, pericytes, and perivascular foot pr ocesses were swollen. Conclusions-The initial lowering of ADC during focal ischemia probably is t he result of not only the acute loss of extracellular fluid and concomitant swelling of various cellular compartments but also concurrent neuronal shr inkage.