Endovascular Perforation Subarachnoid Hemorrhage Fails to Cause Morris Water Maze Deficits in the Mouse

Abstract

Cognitive dysfunction is the primary driver of poor long-term outcome in aneurysmal subarachnoid hemorrhage (SAH) survivors; modeling such deficits preclinically is thus key for mechanistic and translational investigation. Although rat SAH causes long-term deficits in learning and memory, it remains unknown whether similar deficits are seen in the mouse, a species particularly amenable to powerful, targeted genetic manipulation. We thus subjected mice to endovascular perforation SAH and assessed long-term cognitive outcome via the Morris water maze (MWM), the most commonly used metric for rodent neurocognition. No significant differences in MWM performance (by either of two protocols) were seen in SAH versus sham mice. Moreover, SAH caused negligible hippocampal CA1 injury. These results undercut the potential of commonly used methods (of SAH induction and assessment of long-term neurocognitive outcome) for use in targeted molecular studies of SAH-induced cognitive deficits in the mouse.

Human Albumin Improves Long-Term Behavioral Sequelae After Subarachnoid Hemorrhage Through Neurovascular Remodeling

“…Unfortunately, a paucity of studies has attempted to investigate experimental SAH in the chronic phase, and these studies have yielded contradictory results. Some documented that SAH resulted in prolonged behavioral impairments (21,22), whereas other reports suggested a negligible dysfunction (23,24). Such discrepancy may be due to the differences in SAH models, animal species, test paradigms, and time interval between SAH and postoperative assessment.…”

Dendrobium alkaloids prevent Aβ25–35-induced neuronal and synaptic loss via promoting neurotrophic factors expression in mice

“…The ability of spatial learning and memory of the mice was evaluated through the Morris Water Maze (MWM) test (Edwards et al, 2014; Milner et al, 2014). The test was performed on the 14th day after drug administration.…”

Cerebral microcirculatory failure after subarachnoid hemorrhage is reversed by hyaluronidase

“…Future experiments will include behavioral testing, but a new animal model may be necessary as previous studies involving mouse models of SAH have not produced conclusive results. 38 Further work with hyaluronidase in large animal models of SAH, or other agents targeting capillary blood flow, may lead to the development of therapies that can be translated into human treatment. Additionally, the work we presented here is also consistent with the SAH Neurovascular Inversion hypothesis put forward by the Wellman Lab in that the peak severity of neurovascular inversion ($48 h) fits with the time course of microvascular disruption we observed as well as the lack of structural changes (endothelial and astrocytic swelling, perecytic constriction).…”