Minimal long-term neurobehavioral impairments after endovascular perforation subarachnoid hemorrhage in mice

Claudia Fanizzi, Andrew D. Sauerbeck, Mihika Gangolli, Gregory J. Zipfel, David L. Brody, Terrance T. Kummer

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Abstract

Cognitive deficits are among the most severe and pervasive consequences of aneurysmal subarachnoid hemorrhage (SAH). A critical step in developing therapies targeting such outcomes is the characterization of experimentally-tractable pre-clinical models that exhibit multi-domain neurobehavioral deficits similar to those afflicting humans. We therefore searched for neurobehavioral abnormalities following endovascular perforation induction of SAH in mice, a heavily-utilized model. We instituted a functional screen to manage variability in injury severity, then assessed acute functional deficits, as well as activity, anxiety-related behavior, learning and memory, socialization, and depressive-like behavior at sub-acute and chronic time points (up to 1 month post-injury). Animals in which SAH was induced exhibited reduced acute functional capacity and reduced general activity to 1 month post-injury. Tests of anxiety-related behavior including central area time in the elevated plus maze and thigmotaxis in the open field test revealed increased anxiety-like behavior at subacute and chronic time-points, respectively. Effect sizes for subacute and chronic neurobehavioral endpoints in other domains, however, were small. In combination with persistent variability, this led to non-significant effects of injury on all remaining neurobehavioral outcomes. These results suggest that, with the exception of anxiety-related behavior, alternate mouse models are required to effectively analyze cognitive outcomes after SAH.

Original languageEnglish
Article number7569
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017
Externally publishedYes

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Fanizzi, C., Sauerbeck, A. D., Gangolli, M., Zipfel, G. J., Brody, D. L., & Kummer, T. T. (2017). Minimal long-term neurobehavioral impairments after endovascular perforation subarachnoid hemorrhage in mice. Scientific Reports, 7(1), [7569]. https://doi.org/10.1038/s41598-017-07701-y