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We first evaluated CAD and stroke pathology in elderly post\u2010stroke survivors. To simulate CAD, we assessed long\u2010term consequences of bilateral common carotid artery stenosis (BCAS) in mice and exposed them to environmental enrichment (EE).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Histopathological methods were used to determine degrees of CAD (% area stenosis), brain infarct types, sizes and distribution in post\u2010stroke survivors and BCAS mice. Adult male C57BL\/6J mice after BCAS or sham surgery were randomly assigned to standard housing (Std) or limited (3\u00a0h) or full\u2010time (Full) exposure to EE per day for 12\u00a0weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>High frequencies of moderate carotid artery stenosis (51\u201375%) were evident in post\u2010stroke survivors whereas those with severe CAD (&gt;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% (<jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0.01) and thickened carotid artery walls, regardless of EE duration. Remarkably, the total and cortical infarcts declined by &gt;50% in BCAS mice exposed to EE compared with BCAS\u2010Std (<jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>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\u20103\u00a0h and BCAS\u2010Full attenuated coagulation cascade factors including fibrinogen and von Willebrand factor, markers of blood\u2013brain barrier damage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Small cortical and subcortical infarcts were evident in both post\u2010stroke survivors with CAD and BCAS mice. Experimental evidence suggested that moderate exposure to EE is sufficient to reduce subsequent stroke lesions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12550","type":"journal-article","created":{"date-parts":[[2019,4,4]],"date-time":"2019-04-04T17:19:19Z","timestamp":1554398359000},"page":"681-697","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Carotid artery disease in post\u2010stroke survivors and effects of enriched environment on stroke pathology in a mouse model of carotid artery stenosis"],"prefix":"10.1111","volume":"45","author":[{"given":"Y.","family":"Hase","sequence":"first","affiliation":[{"name":"Neurovascular Research Group Institute of Neuroscience Newcastle University Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. 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M.","family":"Allan","sequence":"additional","affiliation":[{"name":"Neurovascular Research Group Institute of Neuroscience Newcastle University Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Ennaceur","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Sunderland Pharmacy School University of Sunderland Sunderland UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Horsburgh","sequence":"additional","affiliation":[{"name":"Centre for Neuroregeneration University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Gallart\u2010Palau","sequence":"additional","affiliation":[{"name":"School of Biological Sciences Nanyang Technological University Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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