Region-specific changes in aquaporin 4 induced by hyperglycemia underlie the differences in cell swelling in the cortex and striatum after cerebral ischemia-reperfusion

Brain edema is a major cause of death in patients who suffer an ischemic stroke. Diabetes has been shown to aggravate brain edema after cerebral ischemia-reperfusion, but few studies have focused on the heterogeneity of this response across different brain regions. Aquaporin 4 plays an important role in the formation and regression of brain edema. Here, we report that hyperglycemia mainly affects the continuity of aquaporin 4 distribution around blood vessels in the cortical penumbra after ischemia-reperfusion; however, in the striatal penumbra, in addition to affecting the continuity of distribution, it also substantially affects the fluorescence intensity and the polarity distribution in astrocytes. Accordingly, hyperglycemia induces a more significant increase in the number of swelling cells in the striatal penumbra than in the cortical penumbra. These results can improve our under-standing of the mechanism underlying the effects of diabetes in cerebral ischemic injury and provide a theo-retical foundation for identification of appropriate therapeutic modalities.

Automated summary

Brain edema is a major cause of death in patients who suffer an ischemic stroke. Diabetes aggravates brain edema after cerebral ischemia-reperfusion, with different effects observed in various brain regions. Hyperglycemia can significantly impact the distribution of aquaporin 4 and increase the number of swelling cells in the striatal penumbra compared to the cortical penumbra.