Subarachnoid Hemorrhage Induces Sub-acute and Early Chronic Impairment in Learning and Memory in Mice

Subarachnoid hemorrhage (SAH) leads to significant long-term cognitive deficits, so-called the post-SAH syndrome. Existing neurological scales used to assess outcomes of SAH are focused on sensory-motor functions. To better evaluate short-term and chronic consequences of SAH, we explored and validated a battery of neurobehavioral tests to gauge the functional outcomes in mice after the circle of Willis perforation-induced SAH. The 18-point Garcia scale, applied up to 4 days, detected impairment only at 24-h time point and showed no significant difference between the Sham and SAH group. A decrease in locomotion was detected at 4-days post-surgery in the open field test but recovered at 30 days in Sham and SAH groups. However, an anxiety-like behavior undetected at 4 days developed at 30 days in SAH mice. At 4-days post-surgery, Y-maze revealed an impairment in working spatial memory in SAH mice, and dyadic social interactions showed a decrease in the sociability in SAH mice, which spent less time interacting with the stimulus mouse. At 30 days after ictus, SAH mice displayed mild spatial learning and memory deficits in the Barnes maze as they committed significantly more errors and used more time to find the escape box but still were able to learn the task. We also observed cognitive dysfunction in the SAH mice in the novel object recognition test. Taken together, these data suggest dysfunction of the limbic system and hippocampus in particular. We suggest a battery of 5 basic behavioral tests allowing to detect neurocognitive deficits in a sub-acute and chronic phase following the SAH.