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Carotid artery disease in post-stroke survivors and effects of enriched environment on stroke pathology in a mouse model of carotid artery stenosis

Lookup NU author(s): Dr Yoshiki Hase, Dr Tuomo Polvikoski, Dr Mai Hase, William Stevenson, Dr Louise Allan, Professor Raj KalariaORCiD


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© 2019 British Neuropathological Society. Aims: Carotid artery disease (CAD) is an important risk factor for stroke. We first evaluated CAD and stroke pathology in elderly post-stroke survivors. To simulate CAD, we assessed long-term consequences of bilateral common carotid artery stenosis (BCAS) in mice and exposed them to environmental enrichment (EE). Methods: Histopathological methods were used to determine degrees of CAD (% area stenosis), brain infarct types, sizes and distribution in post-stroke survivors and BCAS mice. Adult male C57BL/6J mice after BCAS or sham surgery were randomly assigned to standard housing (Std) or limited (3 h) or full-time (Full) exposure to EE per day for 12 weeks. Results: High frequencies of moderate carotid artery stenosis (51–75%) were evident in post-stroke survivors whereas those with severe CAD (>75% stenosis) exhibited greater numbers of cortical rather than subcortical infarcts and, were at higher risk of developing dementia. BCAS in mice reduced cerebral blood flow by 52% (P < 0.01) and thickened carotid artery walls, regardless of EE duration. Remarkably, the total and cortical infarcts declined by >50% in BCAS mice exposed to EE compared with BCAS-Std (P < 0.01). Frontal lobe and cortical strokes were associated with worsening working memory tested in a radial maze paradigm. Proteomic analysis revealed EE, both BCAS-3 h and BCAS-Full attenuated coagulation cascade factors including fibrinogen and von Willebrand factor, markers of blood–brain barrier damage. Conclusion: Small cortical and subcortical infarcts were evident in both post-stroke survivors with CAD and BCAS mice. Experimental evidence suggested that moderate exposure to EE is sufficient to reduce subsequent stroke lesions.

Publication metadata

Author(s): Hase Y, Polvikoski TM, Ihara M, Hase M, Zafar R, Stevenson W, Allan LM, Ennaceur A, Horsburgh K, Gallart-Palau X, Sze SK, Kalaria RN

Publication type: Article

Publication status: Published

Journal: Neuropathology and Applied Neurobiology

Year: 2019

Volume: 45

Issue: 7

Pages: 681-697

Print publication date: 01/12/2019

Online publication date: 04/04/2019

Acceptance date: 19/03/2019

ISSN (print): 0305-1846

ISSN (electronic): 1365-2990

Publisher: Wiley-Blackwell Publishing Ltd


DOI: 10.1111/nan.12550

PubMed id: 30947376


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