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

IntroductionPathophysiological 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.Materials and methodsSAH 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 (CA1 and CA3) using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro-jade B (FJB), respectively.ResultsICP 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%.ConclusionsThe 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.

► Rabbit models for acute SAH studies are lacking. ► SAH is simulated by shunting arterial blood into the subarachnoid space. ► Immediate increase in ICP causes marked decrease in CPP and CBF. ► Apoptosis and neurodegeneration occur in basal cortex and hippocampus. ► The blood-shunt model can be used for the study of early brain injury after SAH.