Social influences on microglial reactivity and neuronal damage after cardiac arrest/cardiopulmonary resuscitation.

Social influences on microglial reactivity and neuronal damage after cardiac arrest/cardiopulmonary resuscitation.
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DOI:
10.1016/j.physbeh.2018.06.012
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发表时间:
2018-10-01
影响因子:
2.9
通讯作者:
DeVries AC
DeVries AC
中科院分区:
医学3区
文献类型:
--
作者:
Gaudier-Diaz MM;Haines AH;Zhang N;DeVries AC

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社会隔离是脑血管疾病的危险因素和预后因素,但其潜在机制尚不明确。本研究探讨了社会环境对全脑缺血后小胶质细胞反应性的影响,以验证社会隔离导致更大的小胶质细胞反应的假设。在心脏骤停/心肺复苏(CA/CPR)或假手术之前,将成年雌性和雄性小鼠成对圈养或社会隔离一周,并且在再灌注2或24小时后,富集小胶质细胞样品并分析基因表达。在2小时时间点,无论饲养条件如何,雌性和雄性的小胶质细胞均表现出缺血诱导的炎症,其特征为肿瘤坏死因子α(TNF-α)、白细胞介素1 β(IL-1β)和白细胞介素6(IL-6)的基因表达增加。然而,在缺血后24小时,社会住房衰减小胶质细胞促炎基因表达的性别特异性的方式。在该时间点,雄性小鼠小胶质细胞中的社会相互作用减弱了缺血诱导的IL-1β和IL-6表达增加,而雌性小鼠中,在细胞表面蛋白主要组织相容性复合体II(MHC II)的小胶质细胞表达中观察到炎症反应的社会减弱。第二项研究检查了缺血性损伤后96小时的行为和生理指标。在该时间点,相对于对照组,CA/CPR后雌性和雄性小鼠表现出运动和探索行为增加。无论性别如何,缺血也会引起神经炎症和神经变性,这两者都受到社会环境的调节。与假手术对照组和成对饲养的CA/CPR组相比,单独CA/CPR组的海马一氧化氮(iNOS)、皮质TNF-α和海马CA 1区Fluoro-Jade C阳性染色细胞计数增加。总之,这些数据表明,雌性和雄性小鼠表现出相似的结果措施和社会调制缺血损伤后96小时,尽管如此,社会环境影响小胶质细胞反应性,以性别特异性的方式,以全脑缺血。
Social isolation presents a risk factor and worsens outcome to cerebrovascular diseases; however, the underlying mechanisms remain underspecified. This study examines the effect of social environment on microglial reactivity after global cerebral ischemia, to test the hypothesis that social isolation leads to greater microglial responses. Adult female and male mice were pair-housed or socially isolated for one week prior to cardiac arrest/cardiopulmonary resuscitation (CA/CPR) or the sham procedure, and following either 2 or 24 hours of reperfusion, microglia samples were enriched and analyzed for gene expression. At the 2-hour time point, microglia from both females and males exhibited ischemia-induced inflammation, characterized by the gene expression increase of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6), regardless of the housing conditions. However, at 24 hours post-ischemia, social housing attenuated microglial pro-inflammatory gene expression in a sex-specific manner. At this time point, the ischemia-induced increased expression of IL-1β and IL-6 was attenuated by social interaction in microglia from male mice, while among female mice social attenuation of the inflammatory response was observed in the microglial expression of cell surface protein major histocompatibility complex II (MHC II). A second study examined behavioral and physiological measures 96 hours after ischemic injury. At this time point, female and male mice displayed increased locomotion and exploratory behavior following CA/CPR relative to controls. Regardless of sex, ischemia also elicited neuroinflammation and neurodegeneration, both of which were modulated by the social environment. Hippocampal nitric oxide (iNOS), cortical TNF-α, and counts of Fluoro-Jade C positive stained cells in the CA1 region of the hippocampus, were increased in the isolated CA/CPR group relative to sham controls and the pair-housed CA/CPR groups. Together, these data indicate that female and male mice exhibit similar outcome measures and social modulation at 96 hours post-ischemic injury, nonetheless, that social environment influences microglial reactivity to global cerebral ischemia in a sex-specific manner.
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