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

Neurosci Lett. 2021 May 29:754:135885. doi: 10.1016/j.neulet.2021.135885. Epub 2021 Apr 15.

Abstract

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 understanding of the mechanism underlying the effects of diabetes in cerebral ischemic injury and provide a theoretical foundation for identification of appropriate therapeutic modalities.

Keywords: Aquaporin 4; Astrocyte; Cortex; Diabetes; Ischemic stroke; Striatum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aquaporin 4 / analysis
  • Aquaporin 4 / metabolism*
  • Brain Edema / blood
  • Brain Edema / etiology
  • Brain Edema / pathology*
  • Cerebral Cortex / pathology
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / complications
  • Humans
  • Hyperglycemia / blood
  • Hyperglycemia / chemically induced
  • Hyperglycemia / complications*
  • Infarction, Middle Cerebral Artery / blood
  • Infarction, Middle Cerebral Artery / complications*
  • Infarction, Middle Cerebral Artery / pathology
  • Male
  • Neostriatum / pathology
  • Rats
  • Reperfusion Injury / blood
  • Reperfusion Injury / etiology
  • Reperfusion Injury / pathology*
  • Streptozocin / administration & dosage
  • Streptozocin / toxicity

Substances

  • Aqp4 protein, rat
  • Aquaporin 4
  • Streptozocin