Carotid Artery Disease in Post-Stroke Survivors and Effects of Enriched Environment on Stroke Pathology in a Mouse Model of Carotid Artery Stenosis.

Hase, Yoshiki, Polvikoski, Tuomo M., Ihara, Masafumi, Hase, Mai, Zafar, Rayyan, Stevenson, William, Allan, Louise M., Ennaceur, Abdelkader, Horsburgh, Karen, Gallart‐Palau, Xavier, Siu, Kwan Sze and Kalaria, Raj N (2019) Carotid Artery Disease in Post-Stroke Survivors and Effects of Enriched Environment on Stroke Pathology in a Mouse Model of Carotid Artery Stenosis. Neuropathology and Applied Neurobiology, 45 (7). pp. 681-697. ISSN 1365-2990

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Abstract

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 (3hrs) 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-3hrs 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.

Item Type: Article
Subjects: Sciences > Biomedical Sciences
Sciences > Health Sciences
Psychology > Neuropsychology
Sciences > Pharmacy and Pharmacology
Divisions: Faculty of Health Sciences and Wellbeing
Faculty of Health Sciences and Wellbeing > School of Pharmacy and Pharmaceutical Sciences
Related URLs:
Depositing User: Abdelkader Ennaceur
Date Deposited: 30 May 2019 10:28
Last Modified: 04 Apr 2020 02:38
URI: http://sure.sunderland.ac.uk/id/eprint/10665
ORCID for Abdelkader Ennaceur: ORCID iD orcid.org/0000-0001-6398-4383

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