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胶质祖细胞分泌蛋白在创伤性脑损伤大鼠模型中的治疗效果。

Therapeutic Efficiency of Proteins Secreted by Glial Progenitor Cells in a Rat Model of Traumatic Brain Injury.

机构信息

Institute of Molecular and Cellular Medicine, RUDN University, 117198 Moscow, Russia.

Research Centre for Medical Genetics, 115478 Moscow, Russia.

出版信息

Int J Mol Sci. 2023 Aug 2;24(15):12341. doi: 10.3390/ijms241512341.

Abstract

Traumatic brain injuries account for 30-50% of all physical traumas and are the most common pathological diseases of the brain. Mechanical damage of brain tissue leads to the disruption of the blood-brain barrier and the massive death of neuronal, glial, and endothelial cells. These events trigger a neuroinflammatory response and neurodegenerative processes locally and in distant parts of the brain and promote cognitive impairment. Effective instruments to restore neural tissue in traumatic brain injury are lacking. Glial cells are the main auxiliary cells of the nervous system, supporting homeostasis and ensuring the protection of neurons through contact and paracrine mechanisms. The glial cells' secretome may be considered as a means to support the regeneration of nervous tissue. Consequently, this study focused on the therapeutic efficiency of composite proteins with a molecular weight of 5-100 kDa secreted by glial progenitor cells in a rat model of traumatic brain injury. The characterization of proteins below 100 kDa secreted by glial progenitor cells was evaluated by proteomic analysis. Therapeutic effects were assessed by neurological outcomes, measurement of the damage volume by MRI, and an evaluation of the neurodegenerative, apoptotic, and inflammation markers in different areas of the brain. Intranasal infusions of the composite protein product facilitated the functional recovery of the experimental animals by decreasing the inflammation and apoptotic processes, preventing neurodegenerative processes by reducing the amounts of phosphorylated Tau isoforms Ser396 and Thr205. Consistently, our findings support the further consideration of glial secretomes for clinical use in TBI, notably in such aspects as dose-dependent effects and standardization.

摘要

外伤性脑损伤占所有身体创伤的 30-50%,是大脑最常见的病理性疾病。脑组织的机械损伤导致血脑屏障破坏和神经元、神经胶质和内皮细胞大量死亡。这些事件引发局部和大脑远处的神经炎症反应和神经退行性过程,并促进认知障碍。缺乏有效的恢复神经组织的工具。神经胶质细胞是神经系统的主要辅助细胞,通过接触和旁分泌机制支持内稳态并确保神经元的保护。神经胶质细胞的分泌组可被视为支持神经组织再生的一种手段。因此,本研究集中于在创伤性脑损伤大鼠模型中,由神经胶质祖细胞分泌的分子量为 5-100 kDa 的复合蛋白的治疗效率。通过蛋白质组学分析评估了由神经胶质祖细胞分泌的小于 100 kDa 的蛋白质的特性。通过神经学结果、通过 MRI 测量损伤体积以及评估大脑不同区域的神经退行性、凋亡和炎症标志物来评估治疗效果。鼻内输注复合蛋白产物通过减少炎症和凋亡过程,通过减少磷酸化 Tau 异构体 Ser396 和 Thr205 的量来阻止神经退行性过程,促进了实验动物的功能恢复。我们的研究结果一致支持进一步考虑神经胶质分泌组在 TBI 中的临床应用,特别是在剂量依赖性效应和标准化等方面。

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