AUTHOR=Zhao Zidan , Hood Rebecca J. , Ong Lin Kooi , Pietrogrande Giovanni , Sanchez Bezanilla Sonia , Warren Kirby E. , Ilicic Marina , Kluge Murielle G. , TeBay Clifford , Ottersen Ole P. , Johnson Sarah J. , Nilsson Michael , Walker Frederick R. 

TITLE=Exploring How Low Oxygen Post Conditioning Improves Stroke-Induced Cognitive Impairment: A Consideration of Amyloid-Beta Loading and Other Mechanisms

JOURNAL=Frontiers in Neurology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.585189

DOI=10.3389/fneur.2021.585189

ISSN=1664-2295

ABSTRACT=Cognitive impairment is a common and disruptive outcome for stroke survivors, which is recognised to be notoriously difficult to treat.  Previously, we have shown that low oxygen post-conditioning (LOPC) improves motor function and limits secondary neuronal loss in the thalamus after experimental stroke.  There is also emerging evidence that LOPC may improve cognitive function post-stroke.  In the current study we aimed to explore how exposure to LOPC may improve cognition post-stroke.  Experimental stroke was induced using photothrombotic occlusion in adult, male C57BL/6 mice.  At 72 hours post-stroke animals were randomly assigned to either normal, atmospheric air or to one of two low oxygen (11% O2) exposure groups (either 8 or 24 hours/day for 14 days).  Cognition was assessed during the treatment phase using a touchscreen based paired associate learning assessment.  At the end of treatment (17 days post-stroke) mice were euthanised and tissue was collected for subsequent histology and biochemical analysis. LOPC (both 8 and 24 hours) enhanced learning and memory in the second week post-stroke when compared with stroke animals exposed to atmospheric air.  Additionally we observed LOPC was associated with lower levels of neuronal loss, the restoration of several of vascular deficits, as well as a reduction in the severity of the amyloid beta (Aβ) burden.  These findings provide further insight into pro-cognitive benefits of LOPC.