title: Heterogeneity of aquaporin-4 localization and expression after focal cerebral ischemia underlies differences in white versus grey matter swelling.
abstract: BACKGROUND
  Ischemic stroke, a major cause of mortality, is frequently accompanied by life-threatening cerebral edema. Aquaporin-4 (Aqp4), an astrocytic transmembrane water channel, is an important molecular contributor to cerebral edema formation. Past studies of Aqp4 expression and localization after ischemia examined grey matter exclusively. However, as white matter astrocytes differ developmentally, physiologically, and molecularly from grey matter astrocytes, we hypothesized that functionally important regional heterogeneity exists in Aqp4 expression and subcellular localization following cerebral ischemia.
  
  
  RESULTS
  Subcellular localization of Aqp4 was compared between cortical and white matter astrocytes in postmortem specimens of patients with focal ischemic stroke versus controls. Subcellular localization and expression of Aqp4 was examined in rats subjected to experimental stroke. Volumetric analysis was performed on the cortex and white matter of rats subjected to experimental stroke. Following cerebral ischemia, cortical astrocytes exhibited reduced perivascular Aqp4 and unchanged Aqp4 protein abundance. In contrast, white matter astrocytes exhibited increased perivascular and plasmalemmal Aqp4 and a 2.2- to 6.2-fold increase in Aqp4 isoform abundance. Ischemic white matter swelled by approximately 40 %, while cortex swelled by approximately 9 %.
  
  
  CONCLUSIONS
  The findings reported here raise the possibility that cerebral white matter may play a heretofore underappreciated role in the formation of cerebral edema following ischemia.
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, 10 S. Pine St., MSTF 634, Baltimore, MD, 21201-1595, USA. Jesse.Stokum@som.umaryland.edu.
authors.forename: Jesse A
authors.initials: JA
authors.lastname: Stokum
authors.affiliation: Departments of Pathology, University of Maryland School of Medicine, 10 S. Pine St., MSTF 634, Baltimore, MD, 21201-1595, USA.
authors.forename: Rupal I
authors.initials: RI
authors.lastname: Mehta
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, 10 S. Pine St., MSTF 634, Baltimore, MD, 21201-1595, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ivanova
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, 10 S. Pine St., MSTF 634, Baltimore, MD, 21201-1595, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Yu
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, 10 S. Pine St., MSTF 634, Baltimore, MD, 21201-1595, USA.
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Gerzanich
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, 10 S. Pine St., MSTF 634, Baltimore, MD, 21201-1595, USA.|Departments of Pathology, University of Maryland School of Medicine, 10 S. Pine St., MSTF 634, Baltimore, MD, 21201-1595, USA.|Department of Physiology, University of Maryland School of Medicine, 10 S. Pine St., MSTF 634, Baltimore, MD, 21201-1595, USA.
authors.forename: J Marc
authors.initials: JM
authors.lastname: Simard
mesh_terms: D000328:Adult; D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism*; D001929:Brain Edema / Q000209:etiology* / Q000473:pathology*; D002545:Brain Ischemia / Q000150:complications* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D066128:Gray Matter / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D012189:Retrospective Studies; D016622:Silver Staining; D066127:White Matter / Q000378:metabolism*
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D018396:Mucin-1; D009419:Nerve Tissue Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1