Anterior circulation mouse model of subarachnoid hemorrhage

Abstract

A model of subarachnoid hemorrhage (SAH) first described in rats where blood is injected into the prechiasmatic cistern was adapted to mice. The hypothesis was that such an anterior circulation SAH model would produce vasospasm of greater severity and longer duration than other mouse models. The goal was to create a mouse model that could then be used in transgenic and knockout animals in order to further knowledge of SAH and vasospasm. A needle was inserted stereotactically into the prechiasmatic cistern and 100 microl autologous arterial blood injected over seconds (n=10). Effects were compared to injection of saline (n=10) or to sham operation (n=7). Monitoring of cerebral blood flow by laser Doppler showed a statistically similar decrease during injection in both groups. 7 days after SAH there was vasospasm of the middle and anterior cerebral arteries (51% reduction in MCA radius in SAH compared to saline-injected group, P<0.009, Student's t-test). In order to determine if SAH in this model was associated with neuronal injury, brains were examined for TUNEL and fluoro-jade-positive cells. 60% of SAH but not saline-injected mice exhibited TUNEL-positive cells in the cerebral cortex and 30% of the SAH but no saline-injected mice had fluoro-jade positive cells in the cortex, hippocampus and dentate gyrus. The model is simple to perform and may be useful for investigating the pathophysiology of SAH.