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超声神经调控可减少多发性硬化症大鼠模型的脱髓鞘。

Ultrasound Neuromodulation Reduces Demyelination in a Rat Model of Multiple Sclerosis.

机构信息

Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.

Division of Neurosurgery, Cheng Hsin General Hospital, Taipei 112, Taiwan.

出版信息

Int J Mol Sci. 2022 Sep 2;23(17):10034. doi: 10.3390/ijms231710034.

Abstract

Microglia, astrocytes, and oligodendrocyte progenitor cells (OPCs) may serve as targets for remyelination-enhancing therapy. Low-intensity pulsed ultrasound (LIPUS) has been demonstrated to ameliorate myelin loss and inhibit neuroinflammation in animal models of brain disorders; however, the underlying mechanisms through which LIPUS stimulates remyelination and glial activation are not well-understood. This study explored the impacts of LIPUS on remyelination and resident cells following lysolecithin (LPC)-induced local demyelination in the hippocampus. Demyelination was induced by the micro-injection of 1.5 μL of 1% LPC into the rat hippocampus, and the treatment groups received daily LIPUS stimulation for 5 days. The therapeutic effects of LIPUS on LPC-induced demyelination were assessed through immunohistochemistry staining. The staining was performed to evaluate remyelination and Iba-1 staining as a microglia marker. Our data revealed that LIPUS significantly increased myelin basic protein (MBP) expression. Moreover, the IHC results showed that LIPUS significantly inhibited glial cell activation, enhanced mature oligodendrocyte density, and promoted brain-derived neurotrophic factor (BDNF) expression at the lesion site. In addition, a heterologous population of microglia with various morphologies can be found in the demyelination lesion after LIPUS treatment. These data show that LIPUS stimulation may serve as a potential treatment for accelerating remyelination through the attenuation of glial activation and the enhancement of mature oligodendrocyte density and BDNF production.

摘要

小胶质细胞、星形胶质细胞和少突胶质细胞前体细胞 (OPC) 可能成为增强髓鞘修复治疗的靶点。低强度脉冲超声 (LIPUS) 已被证明可改善脑疾病动物模型中的髓鞘丢失和抑制神经炎症;然而,LIPUS 刺激髓鞘修复和神经胶质细胞激活的潜在机制尚不清楚。本研究探讨了 LIPUS 在局部溶磷脂酰胆碱 (LPC) 诱导的海马脱髓鞘后对髓鞘修复和固有细胞的影响。通过将 1.5μL 1% LPC 微注射到大鼠海马中来诱导脱髓鞘,治疗组每天接受 5 天的 LIPUS 刺激。通过免疫组织化学染色评估 LIPUS 对 LPC 诱导的脱髓鞘的治疗效果。进行染色以评估髓鞘修复和 Iba-1 染色作为小胶质细胞标志物。我们的数据显示,LIPUS 显著增加了髓鞘碱性蛋白 (MBP) 的表达。此外,免疫组化结果表明,LIPUS 显著抑制了神经胶质细胞的激活,增加了成熟少突胶质细胞的密度,并促进了脑源性神经营养因子 (BDNF) 在病变部位的表达。此外,在 LIPUS 治疗后脱髓鞘病变中可以发现具有各种形态的异源小胶质细胞群体。这些数据表明,LIPUS 刺激可能通过减弱神经胶质细胞的激活、增加成熟少突胶质细胞的密度和增加 BDNF 的产生,成为加速髓鞘修复的一种潜在治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e55d/9456451/345be28cf4b1/ijms-23-10034-g001.jpg

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