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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

Item Type: Article


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.

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Depositing User: Abdelkader Ennaceur


Item ID: 12268
Identification Number:
ISSN: 0361-9230
Official URL:

Users with ORCIDS

ORCID for Hase Yoshiki: ORCID iD
ORCID for Abdelkader Ennaceur: ORCID iD
ORCID for Lucy Craggs: ORCID iD
ORCID for Masafumi Ihara: ORCID iD
ORCID for Karen Horsburgh: ORCID iD
ORCID for Raj N Kalaria: ORCID iD

Catalogue record

Date Deposited: 03 Aug 2020 13:57
Last Modified: 15 Jul 2021 02:38


Author: Hase Yoshiki ORCID iD
Author: Abdelkader Ennaceur ORCID iD
Author: Lucy Craggs ORCID iD
Author: Masafumi Ihara ORCID iD
Author: Karen Horsburgh ORCID iD
Author: Raj N Kalaria ORCID iD
Author: Stevenson Williams
Author: Wilson Elle
Author: Hollins Annabel
Author: Hase Mai
Author: Williams Stevenson
Author: Yoshiki Hase
Author: Elle Wilson
Author: Annabel Hollins
Author: Mai Hase
Author: Abdelkader Ennaceur
Author: Lucy Craggs
Author: Masafumi Ihara
Author: Karen Horsburgh
Author: Raj N Kalaria

University Divisions

Faculty of Health Sciences and Wellbeing
Faculty of Health Sciences and Wellbeing > School of Pharmacy and Pharmaceutical Sciences


Sciences > Biomedical Sciences
Sciences > Health Sciences
Psychology > Neuropsychology
Sciences > Pharmacy and Pharmacology

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