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Effects of environmental enrichment on white matter glial responses in a mouse model of chronic cerebral hypoperfusion

Lookup NU author(s): Dr Yoshiki HaseORCiD, Dr Lucy Craggs, Dr Mai Hase, William Stevenson, Janet Slade, Dianne Lopez, Dr Aiqing Chen, Dr Di Liang, Arthur Oakley, Dr Masafumi Ihara, Professor Raj KalariaORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2017 The Author(s). Background: This study was designed to explore the beneficial effects of environmental enrichment (EE) on white matter glial changes in a mouse model of chronic cerebral hypoperfusion induced by bilateral common carotid artery stenosis (BCAS). Methods: A total of 74 wild-type male C57BL/6J mice underwent BCAS or sham surgery. One week after surgery, the mice were randomly assigned into three different groups having varied amounts of EE-standard housing with no EE conditions (std), limited exposure with 3 h EE a day (3 h) and full-time exposure to EE (full) for 12 weeks. At 16 weeks after BCAS surgery, behavioural and cognitive function were assessed prior to euthanasia. Brain tissues were analysed for the degree of gliosis including morphological changes in astrocytes and microglia. Results: Chronic cerebral hypoperfusion (or BCAS) increased clasmatodendrocytes (damaged astrocytes) with disruption of aquaporin-4 immunoreactivity and an increased degree of microglial activation/proliferation. BCAS also impaired behavioural and cognitive function. These changes were significantly attenuated, by limited exposure compared to full-time exposure to EE. Conclusions: Our results suggest that moderate or limited exposure to EE substantially reduced glial damage/activation. Our findings also suggest moderate rather than continuous exposure to EE is beneficial for patients with subcortical ischaemic vascular dementia characterised by white matter disease-related inflammation.

Publication metadata

Author(s): Hase Y, Craggs L, Hase M, Stevenson W, Slade J, Lopez D, Mehta R, Chen A, Liang D, Oakley A, Ihara M, Horsburgh K, Kalaria RN

Publication type: Article

Publication status: Published

Journal: Journal of Neuroinflammation

Year: 2017

Volume: 14

Issue: 1

Online publication date: 11/04/2017

Acceptance date: 23/03/2017

Date deposited: 10/05/2017

ISSN (electronic): 1742-2094

Publisher: BioMed Central Ltd


DOI: 10.1186/s12974-017-0850-5


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Funder referenceFunder name
ARUK PG2013-22