Cyclooxygenase-2 mRNA expression is associated with c-fos mRNA expression and transient water ADC reduction detected with diffusion MRI during acute focal ischemia in rats

Cyclooxygenase-2 (COX-2) plays an important role in the development of injury during cerebral ischemia and inhibition of its activity can reduce infarct size. COX-2 expression during acute ischemia is caused by activation of post-synaptic glutamate receptors, which occurs during spreading depression and ischemic depolarization. Both of these phenomena cause a reduction in the apparent diffusion coefficient of water (ADC), which can be detected with diffusion-weighted magnetic resonance imaging. The reduction is believed to be caused by cellular swelling that occurs as cells depolarize. The goal of this work was to determine the spatial relationship between cyclooxygenase-2 mRNA (cox-2) expression, c-fos mRNA expression and ADC reduction during acute focal cerebral ischemia. Adult rats were subjected to either 30- or 60-min permanent occlusion of the middle cerebral artery. A 2-Tesla scanner was used to acquire diffusion-weighted echo-planar images throughout the ischemic period, which were used to calculate ADC maps. Cox-2 and c-fos mRNA were detected with (35)S in situ hybridization. The results indicate that, for rats subjected to 60-min ischemia, cox-2 was observed in superficial layers of cortex, where transient ADC reduction and c-fos expression were observed. The same was true for most rats subjected to 30-min ischemia. However, in a small number of rats of the 30-min group, cox-2 mRNA expression was observed in regions exhibiting transient and persistent ADC reduction with no c-fos expression. The results suggest that cox-2 mRNA expression during acute MCA occlusion is caused by either or both spreading depression and transient ischemic depolarization.