title: Hyperglycemia exacerbates intracerebral hemorrhage via the downregulation of aquaporin-4: temporal assessment with magnetic resonance imaging.
abstract: OBJECTIVE
  Intracerebral hemorrhage (ICH) is associated with high mortality and neurological deficits, and concurrent hyperglycemia usually worsens clinical outcomes. Aquaporin-4 (AQP-4) is important in cerebral water movement. Our aim was to investigate the role of AQP-4 in hyperglycemic ICH.
  
  
  METHODS
  Hyperglycemia was induced by intraperitoneal injection of streptozotocin (STZ; 60 mg/kg) in adult Sprague-Dawley male rats. ICH was induced by stereotaxic infusion of collagenase/heparin into the right striatum. One set of rats was repeatedly monitored by MRI at 1, 4, and 7 days after ICH induction so as to acquire information on the formation of hematoma and edema. Another set of rats was killed and brains were examined for differences in the degree of hemorrhage and edema, water content, blood-brain barrier destruction, and AQP-4 expression.
  
  
  RESULTS
  Hyperglycemia ICH rats exhibited increased brain water content, more severe blood-brain barrier destruction, and greater vasogenic edema as seen on diffusion-weighted MRI. Significant downregulation of AQP-4 was observed in STZ-treated rats after ICH as compared with non-STZ-treated rats. Apoptosis was greater on day 1 after ICH in STZ-treated rats.
  
  
  CONCLUSIONS
  The expression of AQP-4 in the brain is downregulated in hyperglycemic rats as compared with normoglycemic rats after ICH. This change is accompanied by increased vasogenic brain edema and more severe blood-brain barrier destruction.
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Cheng-Di
authors.initials: CD
authors.lastname: Chiu
authors.forename: Chiao-Chi V
authors.initials: CC
authors.lastname: Chen
authors.forename: Chiung-Chyi
authors.initials: CC
authors.lastname: Shen
authors.forename: Li-Te
authors.initials: LT
authors.lastname: Chin
authors.forename: Hsin-I
authors.initials: HI
authors.lastname: Ma
authors.forename: Hao-Yu
authors.initials: HY
authors.lastname: Chuang
authors.forename: Der-Yang
authors.initials: DY
authors.lastname: Cho
authors.forename: Chi-Hong
authors.initials: CH
authors.lastname: Chu
authors.forename: Chen
authors.initials: C
authors.lastname: Chang
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000502:physiology*; D001929:Brain Edema / Q000453:epidemiology / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000453:epidemiology* / Q000503:physiopathology*; D017364:Collagenases / Q000008:administration & dosage / Q000009:adverse effects; D015897:Comorbidity; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology*; D006406:Hematoma / Q000453:epidemiology / Q000473:pathology; D006493:Heparin / Q000008:administration & dosage / Q000009:adverse effects; D006943:Hyperglycemia / Q000139:chemically induced / Q000453:epidemiology* / Q000503:physiopathology*; D015994:Incidence; D057967:Infusions, Intraventricular; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D013311:Streptozocin; D006493:Heparin; D017364:Collagenases
keywords: aquaporin-4; hyperglycemia; intracerebral hemorrhage; magnetic resonance imaging