title: Hyperglycemia Aggravates Cerebral Vasospasm after Subarachnoid Hemorrhage in a Rat Model.
abstract: BACKGROUND
  Hyperglycemia is common and showed to be risky for poor prognosis in patients with subarachnoid hemorrhage (SAH). However, the causality and mechanism underlying this observation are not well established.
  
  
  OBJECTIVE
  To investigate the relationship between hyperglycemia and cerebral vasospasm with its pathogenesis in a rat model of SAH.
  
  
  METHODS
  One-shot SAH model was employed in male Sprague-Dawley rats. Hyperglycemia was triggered by intraperitoneal streptozotocin administration (50 mg/kg) 7 days before SAH induction. The severity of cerebral vasospasm was determined by the cross-sectional area of basilar artery (BA) in male rats randomly assigned to 1 of 4 groups: control, hyperglycemia only, SAH only, and SAH with hyperglycemia. The expression of endothelial nitric oxide synthase (eNOS) and induced nitric oxide synthase (iNOS) in the BA were analyzed by immunohistochemistry.
  
  
  RESULTS
  The mean (standard deviation) blood glucose level was 433.0 (98.3) and 156.5 (31.7) mg/dL in streptozotocin -treated and untreated rats, respectively. Hyperglycemic rats exhibited poorer neurobehavioral performance than normoglycemic rats when subjected to SAH. Hyperglycemia-mediated exacerbation of vasospasm was evident by the greater decrease in the BA cross-sectional area in the hyperglycemic SAH group than in the SAH only group. Furthermore, there was more decreased expression of eNOS and increased expression of iNOS within the vessels of the hyperglycemic SAH rats.
  
  
  CONCLUSIONS
  Hyperglycemia exacerbated cerebral vasospasm and was associated with poorer neurological outcomes following SAH. Our findings also suggested the nitric oxide pathway as a potential underlying mechanism via the dysregulation of eNOS and iNOS.
authors.affiliation: Graduate Institute of Medicine, Col-lege of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Depart-ment of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Graduate Institute of Medicine, Col-lege of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Surgery, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan.
authors.forename: Chia-Li
authors.initials: CL
authors.lastname: Chung
authors.affiliation: Graduate Institute of Medicine, Col-lege of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Hung-Pei
authors.initials: HP
authors.lastname: Tsai
authors.affiliation: Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Shu-Chuan
authors.initials: SC
authors.lastname: Wu
authors.affiliation: Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Surgery, Kaohsiung Municipal Ta Tung Hospital, Kaohsiung, Taiwan.
authors.forename: Chih-Zen
authors.initials: CZ
authors.lastname: Chang
authors.affiliation: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Pathology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chee-Yin
authors.initials: CY
authors.lastname: Chai
authors.affiliation: Department of Neurosurgery, Chiayi Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Chiayi, Taiwan.
authors.forename: Tao-Chen
authors.initials: TC
authors.lastname: Lee
authors.affiliation: Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Neurosurgery, University of Virginia, Charlottesville, Virginia.
authors.forename: Aij-Lie
authors.initials: AL
authors.lastname: Kwan
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004195:Disease Models, Animal; D006943:Hyperglycemia / Q000097:blood* / Q000150:complications / Q000473:pathology; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000097:blood* / Q000150:complications / Q000473:pathology; D020301:Vasospasm, Intracranial / Q000097:blood* / Q000209:etiology / Q000473:pathology
chemical_list: D001786:Blood Glucose; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III
keywords: Cerebral vasospasm; Hyperglycemia; Nitric oxide synthase; Subarachnoid hemorrhage