Carotid artery disease in post-stroke survivors and effects of enriched environment on stroke pathology in a mouse model of carotid artery stenosis.
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.
['Hase|Y|Y|', 'Polvikoski|T M|TM|', 'Ihara|M|M|', 'Hase|M|M|', 'Zafar|R|R|', 'Stevenson|W|W|', 'Allan|L M|LM|', 'Ennaceur|A|A|', 'Horsburgh|K|K|', 'Gallart-Palau|X|X|', 'Sze|S K|SK|', 'Kalaria|R N|RN|0000-0001-7907-4923']
D000368:Aged D000369:Aged, 80 and over D000818:Animals D002340:Carotid Artery Diseases D016893:Carotid Stenosis D002560:Cerebrovascular Circulation D004195:Disease Models, Animal D005260:Female D006801:Humans D008297:Male D051379:Mice D040901:Proteomics D020521:Stroke
carotid artery disease stroke environmental enrichment cerebrovascular pathology post-stroke dementia vascular brain injury