Chronological morphological changes in central nervous system induced by chronic electrical sensorimotor cortex stimulation in rats

运动皮质刺激（MCS）已被用作各种疾病的治疗选择，如医学上难治性疼痛、中风后偏瘫和运动障碍。然而，其作用的确切机制仍然未知。本研究通过观察星形胶质细胞的变化，探讨长期慢性MCS的影响。在成年大鼠感觉运动皮层上方硬脑膜上植入四极刺激电极，连续刺激3小时、1周、4周、8周。采用小胶质细胞免疫组化（离子钙结合接头分子1 （Iba1）免疫反应染色）、星形胶质细胞免疫组化（胶质纤维酸性蛋白（GFAP）免疫反应染色）、神经元变性组织化学（氟玉B （FJB）染色）观察长期慢性MCS的形态学变化。Iba1染色和FJB染色未显示Iba1阳性的小胶质细胞改变或神经变性。连续MCS后，受刺激半球皮层和丘脑中gfap阳性星形胶质细胞增大，数量增加。提示慢性电刺激可持续激活星形胶质细胞，并引起形态学和定量变化。这些变化可能有助于MCS诱导神经可塑性效应的机制。

Motor cortex stimulation (MCS) has been utilized as a treatment option for various disorders such as medically refractory pain, poststroke hemiplegia, and movement disorders. However, the precise mechanisms underlying its effects remain unknown. In this study, the effects of long-term chronic MCS were investigated by observing the changes in astrocytes. A quadripolar stimulation electrode was implanted on the dura over the sensorimotor cortex of adult rats, and the cortex was continuously stimulated for three hours, one week, four weeks, and eight weeks. Immunohistochemical staining of microglia (ionized calcium-binding adaptor molecule 1 (Iba1) immunoreactive staining) and astrocytes (glial fibrillary acidic protein (GFAP) -immunoreactive staining), and neuronal degeneration histochemistry (Fluoro-Jade B (FJB) staining) were carried out to investigate the morphological changes following long-term chronic MCS. Iba1 staining and FJB staining showed no evidence of Iba1-positive microglial changes or neurodegeneration. Following continuous MCS, GFAP-positive astrocytes were enlarged and their number increased in the cortex and the thalamus of the stimulated hemisphere. These findings indicate that chronic electrical stimulation can continuously activate astrocytes and result in morphological and quantitative changes. These changes may contribute to the mechanisms underlying the neuroplasticity effect induced by MCS.