title: A new rabbit model for the study of early brain injury after subarachnoid hemorrhage.
abstract: BACKGROUND
  Pathophysiological disturbances during subarachnoid hemorrhage (SAH) and within the first few days thereafter are responsible for significant brain damage. Early brain injury (EBI) after SAH has become the focus of current research activities. The purpose of the present study was to evaluate whether a novel rabbit SAH model provokes EBI by means of neuronal degeneration, brain tissue death, and apoptosis in cerebral vascular endothelial cells.
  
  
  METHODS
  SAH was performed using an extra-intracranial blood shunt. Intracranial pressure (ICP), cerebral perfusion pressure (CPP), and bilateral regional cerebral blood flow (rCBF) were continuously measured. Apoptosis and neurodegeneration were detected 24h post-SAH in basilar artery endothelial cells, bilateral basal cortex, and hippocampus (CA1 and CA3) using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro-jade B (FJB), respectively.
  
  
  RESULTS
  ICP increase caused a CPP decrease to almost zero (8±5mmHg) and decreases in left and right rCBF to 23±8% and 19±9% of their baseline values. TUNEL- and FJB-stained sections revealed significant apoptosis and neurodegeneration in both basal cortex and hippocampal regions compared to sham-operated animals. The apoptotic index in basilar artery endothelial cells was 74%±11%.
  
  
  CONCLUSIONS
  The blood shunt rabbit SAH model elicits acute physiological dearrangements and provokes marked and consistent early damage to the hippocampus, basal cortex, and cerebral vasculature 24h thereafter. These findings make the model a valid tool for investigation of pre-vasospasm pathophysiological mechanisms and novel treatment modalities.
authors.affiliation: Department of Intensive Care Medicine, Bern University Hospital and University of Bern, Bern, Switzerland. serge.marbacher@ksa.ch
authors.forename: Serge
authors.initials: S
authors.lastname: Marbacher
authors.forename: Lukas
authors.initials: L
authors.lastname: Andereggen
authors.forename: Volker
authors.initials: V
authors.lastname: Neuschmelting
authors.forename: Hans Rudolf
authors.initials: HR
authors.lastname: Widmer
authors.forename: Michael
authors.initials: M
authors.lastname: von Gunten
authors.forename: Jukka
authors.initials: J
authors.lastname: Takala
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Jakob
authors.forename: Javier
authors.initials: J
authors.lastname: Fandino
mesh_terms: D000208:Acute Disease; D000818:Animals; D002545:Brain Ischemia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D009410:Nerve Degeneration / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D014661:Vasoconstriction / Q000502:physiology