Long-Term Effects of Experimental Carotid Stenosis on Hippocampal Infarct Pathology, Neurons and Glia and Amelioration by Environmental Enrichment

Williams, Stevenson, Yoshiki, Hase, Elle, Wilson, Annabel, Hollins, Mai, Hase, Ennaceur, Abdelkader, Craggs, Lucy, Ihara, Masafumi, Horsburgh, Karen and Kalaria, Raj N (2020) Long-Term Effects of Experimental Carotid Stenosis on Hippocampal Infarct Pathology, Neurons and Glia and Amelioration by Environmental Enrichment. Brain Research Bulletin, 163. pp. 72-83. ISSN 0361-9230

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Abstract

Hippocampal atrophy and pathology are common in ageing-related disorders and associated with cognitive impairment and dementia. We explored whether environmental enrichment (EE) ameliorated the pathological sequelae in the hippocampus subsequent to chronic cerebral hypoperfusion induced by bilateral common carotid artery stenosis (BCAS). Seventy-four male C57BL/6 J mice underwent BCAS or sham surgery. One-week after surgery, mice were exposed to three different degrees of EE; either standard housing conditions (std), limited 3-hour exposure to EE per day (3h) or full-time exposure to EE (full) for 3 months. Four months after surgery, the hippocampus was examined for the extent of vascular brain injury and neuronal and glial changes. Results showed that long-term BCAS induced strokes, most often in CA1 subfield, reduced 40-50% CA1 neurons (P<0.01) and increased microglia/macrophage in CA1-CA3 subfields (P<0.02). Remarkably, both 3h and full-time EE regimes attenuated hippocampal neuronal death and repressed recurrent strokes with complete prevention of larger infarcts in mice on full-time EE (P<0.01). Full-time EE also reduced astrocytic clasmatodendrosis and microglial/macrophage activation in all CA subfields. Our results suggest that exposure to EE differentially reduces long-term hypoperfusive hippocampal damage. The implementation of even limited EE may be beneficial for patients diagnosed with vascular cognitive impairment.

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: 03 Aug 2020 13:57
Last Modified: 24 Aug 2020 12:42
URI: http://sure.sunderland.ac.uk/id/eprint/12268
ORCID for Hase Yoshiki: ORCID iD orcid.org/0000-0002-9538-905X
ORCID for Abdelkader Ennaceur: ORCID iD orcid.org/0000-0001-6398-4383
ORCID for Lucy Craggs: ORCID iD orcid.org/0000-0001-9192-1072
ORCID for Masafumi Ihara: ORCID iD orcid.org/0000-0002-7102-4048
ORCID for Karen Horsburgh: ORCID iD orcid.org/0000-0002-9620-3691
ORCID for Raj N Kalaria: ORCID iD orcid.org/0000-0001-7907-4923

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