A new rabbit model for the study of early brain injury after subarachnoid hemorrhage

作者：Marbacher Serge^*; Andereggen Lukas; Neuschmelting Volker; Widmer Hans Rudolf; von Gunten Michael; Takala Jukka; Jakob Stephan M; Fandino Javier

来源：Journal of Neuroscience Methods, 2012, 208(2): 138-145.

DOI：10.1016/j.jneumeth.2012.05.010

• Rabbit model
• Subarachnoid hemorrhage
• Early brain injury
• Neuronal death
• Cerebral blood flow

Introduction: 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. %26lt;br%26gt;Materials and 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 24 h post-SAH in basilar artery endothelial cells, bilateral basal cortex, and hippocampus (CM and CA3) using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro-jade B (FJB), respectively. %26lt;br%26gt;Results: ICP increase caused a CPP decrease to almost zero (8 +/- 5 mmHg) 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%. %26lt;br%26gt;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 24 h thereafter. These findings make the model a valid tool for investigation of pre-vasospasm pathophysiological mechanisms and novel treatment modalities.

• 出版日期2012-7-15