Hase Yoshiki, Craggs Lucinda, Hase Mai, Stevenson William, Slade Janet, Lopez Dianne, Mehta Rubin, Chen Aiqing, Liang Di, Oakley Arthur, Ihara Masafumi, Horsburgh Karen, Kalaria Raj N
Neurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK.
Department of Stroke and Cerebrovascular Diseases, National Cerebral and Cardiovascular Centre, Osaka, Japan.
J Neuroinflammation. 2017 Apr 11;14(1):81. doi: 10.1186/s12974-017-0850-5.
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.
本研究旨在探讨环境富集（EE）对双侧颈总动脉狭窄（BCAS）诱导的慢性脑灌注不足小鼠模型中白质胶质细胞变化的有益影响。
总共74只野生型雄性C57BL/6J小鼠接受了BCAS手术或假手术。手术后一周，将小鼠随机分为三组，分别给予不同程度的EE——无EE条件的标准饲养（std）、每天3小时EE的有限暴露（3h）和12周的EE全时暴露（full）。在BCAS手术后16周，在安乐死之前评估行为和认知功能。分析脑组织的胶质增生程度，包括星形胶质细胞和小胶质细胞的形态变化。
慢性脑灌注不足（或BCAS）增加了破裂性树突状细胞（受损星形胶质细胞），伴有水通道蛋白-4免疫反应性破坏和小胶质细胞活化/增殖程度增加。BCAS还损害了行为和认知功能。与EE全时暴露相比，有限暴露使这些变化显著减轻。
我们的结果表明，适度或有限暴露于EE可显著减少胶质细胞损伤/活化。我们的研究结果还表明，适度而非持续暴露于EE对以白质疾病相关炎症为特征的皮质下缺血性血管性痴呆患者有益。
