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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
Author(s) -
Hase Y.,
Polvikoski T. M.,
Ihara M.,
Hase M.,
Zafar R.,
Stevenson W.,
Allan L. M.,
Ennaceur A.,
Horsburgh K.,
GallartPalau X.,
Sze S. K.,
Kalaria R. N.
Publication year - 2019
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12550
Subject(s) - medicine , stroke (engine) , stenosis , cardiology , common carotid artery , carotid artery disease , pathology , surgery , carotid arteries , carotid endarterectomy , mechanical engineering , engineering
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.