Repetitive transcranial magnetic stimulation (rTMS), a non-invasive form of brain stimulation, has shown experimental and clinical efficacy in a range of neuromodulatory models, even when delivered at low intensity (i.e. subthreshold for action potential generation). After central nervous system (CNS) injury, studies suggest that reactive astrocytes and microglia can have detrimental but also beneficial effects; thus modulating glial activity, for example through application of rTMS, could potentially be a useful therapeutic tool following neurotrauma. Immunohistochemistry was used to measure the effect of low intensity rTMS (LI-rTMS) on GFAP (astrocyte), IBA1 (microglial), and CS56 (proteoglycan) expression in a unilateral penetrating cortical stab injury model of glial scarring in young adult and aged male and female C57BL6/J mice. Mice received contralateral low frequency, ipsilateral low frequency, ipsilateral high frequency or sham LI-rTMS (4-5mT intensity), for two weeks following injury. There was no significant difference in the overall volume of tissue containing GFAP positive (+) astrocytes, IBA1+ microglia, or proteoglycan expression, between sham and LI-rTMS-treated mice of all ages and sex. Importantly however, the density of GFAP+ astrocytes and IBA1+ microglia immediately adjacent to the injury was significantly reduced following ipsilateral low and high frequency stimulation in adult and aged females (p≤0.05), but was significantly increased in adult and aged males (p≤0.05). LI-rTMS effects were generally of greater magnitude in aged mice compared to young adult mice. These results suggest that sex differences need to be factored into therapeutic rTMS protocols. In particular, more work analyzing frequency and intensity specific effects, especially in relation to age and sex, is required to determine how rTMS can best be used to modify glial reactivity and phenotype following neurotrauma.

译文

重复经颅磁刺激 (rTMS) 是一种非侵入性的脑刺激形式,即使在低强度 (即动作电位产生的亚阈值) 下,也已在一系列神经调节模型中显示出实验和临床功效。中枢神经系统 (CNS) 损伤后,研究表明反应性星形胶质细胞和小胶质细胞可能具有有害但有益的作用; 因此,例如通过应用rTMS调节神经胶质活性,可能是神经创伤后有用的治疗工具。免疫组织化学用于测量低强度rTMS (LI-rTMS) 对年轻成年和老年C57BL6/J小鼠单侧穿透性皮质瘢痕损伤模型中GFAP (星形胶质细胞),IBA1 (小胶质细胞) 和CS56 (蛋白聚糖) 表达的影响。损伤后两周,小鼠接受对侧低频,同侧低频,同侧高频或假LI-rTMS (4-5mT强度)。在所有年龄和性别的sham和LI-rTMS治疗的小鼠之间,含有GFAP阳性 () 星形胶质细胞,IBA1小胶质细胞或蛋白聚糖表达的组织的总体积均无显着差异。然而,重要的是,在同侧低频和高频刺激后,与损伤紧邻的GFAP + 星形胶质细胞和IBA1 + 小胶质细胞的密度在成年和老年女性中显著降低 (p ≤ 0.05),但在成年和老年男性中显著增加 (p ≤ 0.05)。与年轻的成年小鼠相比,老年小鼠的LI-rTMS效应通常更大。这些结果表明,需要将性别差异纳入治疗性rTMS方案。特别是,需要更多的工作来分析频率和强度的特定影响,尤其是与年龄和性别有关的影响,以确定rTMS如何最好地用于改变神经创伤后的神经胶质反应性和表型。

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