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

Abstract

2019) Neuropathology and Applied Neurobiology 45, 681-697 Carotid artery disease in post-stroke survivors and effects of enriched environment on stroke pathology in a mouse model of carotid artery stenosisAims: 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 poststroke survivors with CAD and BCAS mice. Experimental evidence suggested that moderate exposure to EE is sufficient to reduce subsequent stroke lesions.

Small vessel disease pathological changes in neurodegenerative and vascular dementias concomitant with autonomic dysfunction

“…In comparison to the neurodgenerative dementias, VaD subjects bear greater degrees of large vessel disease, that is, intracranial and extracranial atherosclerotic disease. In a recent study , we noted that regardless of severity of carotid artery stenosis, most of the infarcts were small (<5mm in size) and most were located in the cerebral cortex. In a previous study, it was further noted that cerebral atherosclerosis was not only expectedly associated with cystic infarcts but importantly microinfarcts .…”

Loss of capillary pericytes and the blood–brain barrier in white matter in poststroke and vascular dementias and Alzheimer’s disease

“…Neuropathological assessment was carried out as described previously (32). Briefly, hematoxylin and eosin (H&E) staining was used for assessment of structural integrity and infarcts, Nissl and Luxol Fast blue staining for cellular patterns and myelin loss, Bielschowsky’s silver method and amyloid‐β immunohistochemistry for ABC rating of neuritic plaques, Gallays stain for neuritic pathology and tau immunohistochemistry for Braak staging of neurofibrillary tangles.…”

“…Increased volumes of WMHs are associated with vascular disease, disability, cognitive impairment and death (17, 24, 34, 41). WMHs have been largely attributed to cerebral small vessel disease (SVD) but large vessel disease may also contribute to WM lesions (5, 17, 32). We have previously identified the cell and molecular changes within the gliovascular unit that incorporates the blood–brain barrier (BBB) in the deep frontal WM of elderly patients who develop dementia after stroke (13, 30).…”

Alzheimer’s disease progression characterized by alterations in the molecular profiles and biogenesis of brain extracellular vesicles

“…However, to the best of our knowledge, proteome-wide investigation of alterations in brain EV composition and biogenesis related to AD progression is still pending. Thus, based on our experience with the application of discovery-driven proteomics approaches for the study of neurodegeneration [17][18][19][20][21][22][23] and state-of-the-art methodologies for the study of CNS-EV in vivo [14,24], in this work, we investigate how AD progression could be underpinned by proteome-wide alterations in brain EV and by changes in the biogenesis of these vesicles.…”