Regional Variations in the Apparent Diffusion Coefficient and the Intracellular Distribution of Water in Rat Brain During Acute Focal Ischemia

Abstract

Background and Purpose— The apparent diffusion coefficient of water (ADC) rapidly drops in ischemic tissue after cerebral artery occlusion. This acute drop is thought to be caused by the loss of extracellular fluid and the gain of intracellular fluid. To test the latter possibility, changes in ADC and the size of several cellular compartments were assessed in 3 regions of rat brain at the end of 90 minutes of focal cerebral ischemia. Methods— One middle cerebral artery was permanently occluded in 8 Sprague-Dawley rats; sham occlusions were performed in 2 other rats. ADC maps were generated 90 minutes later, and the brains were immediately perfusion fixed. Three regions of interest (ROIs) were defined on the basis of ADC range. Various neuronal, astrocytic, and capillary compartments in each ROI were quantified with light and electron microscopy. Results— At the end of 90 minutes of ischemia, mean ADC was normal in the cortex of sham-operated rats and the contralateral cortex of ischemic rats (ROI-a), 25% lower in the ipsilateral frontoparietal cortex (ROI-b), and 45% lower in the ischemic lateral caudoputamen (ROI-c). At this time, the frequency 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 ROI-c, 40% and 60% of the neurons, respectively, were shrunken; the shrunken neurons were ≈25% smaller in ROI-c than in ROI-b. In these areas, many capillary endothelial cells, pericytes, and perivascular foot processes were swollen. Conclusions— The initial lowering of ADC during focal ischemia probably is the result of not only the acute loss of extracellular fluid and concomitant swelling of various cellular compartments but also concurrent neuronal shrinkage.