title: Effects of environmental enrichment on white matter glial responses in a mouse model of chronic cerebral hypoperfusion.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Neurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hase
authors.affiliation: Neurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK.
authors.forename: Lucinda
authors.initials: L
authors.lastname: Craggs
authors.affiliation: Neurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK.
authors.forename: Mai
authors.initials: M
authors.lastname: Hase
authors.affiliation: Neurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK.
authors.forename: William
authors.initials: W
authors.lastname: Stevenson
authors.affiliation: Neurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK.
authors.forename: Janet
authors.initials: J
authors.lastname: Slade
authors.affiliation: Neurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK.
authors.forename: Dianne
authors.initials: D
authors.lastname: Lopez
authors.affiliation: Neurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK.
authors.forename: Rubin
authors.initials: R
authors.lastname: Mehta
authors.affiliation: Neurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK.
authors.forename: Aiqing
authors.initials: A
authors.lastname: Chen
authors.affiliation: Neurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK.
authors.forename: Di
authors.initials: D
authors.lastname: Liang
authors.affiliation: Neurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK.
authors.forename: Arthur
authors.initials: A
authors.lastname: Oakley
authors.affiliation: Department of Stroke and Cerebrovascular Diseases, National Cerebral and Cardiovascular Centre, Osaka, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ihara
authors.affiliation: Centre for Neuroregeneration, University of Edinburgh, Edinburgh, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Horsburgh
authors.affiliation: Neurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK. raj.kalaria@newcastle.ac.uk.
authors.forename: Raj N
authors.initials: RN
authors.lastname: Kalaria
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D016893:Carotid Stenosis / Q000150:complications* / Q000473:pathology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004777:Environment; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000209:etiology / Q000473:pathology; D056784:Leukoencephalopathies / Q000209:etiology / Q000451:nursing / Q000473:pathology*; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D009425:Nesting Behavior / Q000502:physiology; D009457:Neuroglia / Q000378:metabolism*; D013997:Time Factors
chemical_list: C491049:Aif1 protein, mouse; D051401:Aquaporin 4; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins
keywords: Animal model; Chronic cerebral hypoperfusion; Clasmatodendrosis; Environmental enrichment; Glial activation/proliferation