Incidence and factors in delayed neurological deficits after subarachnoid hemorrhage in mice

Abstract

Objective: Delayed cerebral ischemia (DCI) is one of the most feared complications in aneurysmal subarachnoid hemorrhage (SAH). Animal models are crucial to studying the disease mechanisms and potential treatments. DCI in rodents was thought to not exist; herein we examine literature and our experience with DCI in rodents. Methods: Daily behavioral performance was assessed every day from day 1 to up to 7 days post-SAH on mice from 5 different studies that used the endovascular perforation model. Performance was graded using an 8-test sensorimotor neuroscore previously described. The daily neuroscore was then used to identify the incidence and timing of delayed neurological deficits (DND), a clinical surrogate for DCI. A total number of 298 mice (134 males, 164 females) were subjected to SAH. Fifty-one mice had histological staining done to identify infarct volume. Results: The overall incidence of DND was 33.9%; 27.6% in males and 39.0% in females, but this difference was not statistically significant. The overall incidence of delayed death was 21.1%, and there was no significant difference for delayed mortality in females versus male mice. There is a non-statistically significant trend towards increased infarct volume in mice suffering DND. Conclusions: Mice with endovascular puncture induced SAH develop DND at rates comparable to human patients. Future work needs to correlate the DND seen with decreased regional cerebral blood flow, another hallmark of DCI, but in spite of this need, researchers may use the murine models to test therapies for DCI after SAH.

Keywords

• Subarachnoid hemorrhage
• Delayed cerebral ischemia
• Delayed neurological deficits
• DCI
• SAH