The underlying mechanisms for the beneficial effects exerted by bone marrow-mesenchymal stem cells (BM-MSCs) in treating repetitive traumatic brain injury (rTBI)-induced long-term sensorimotor/cognitive impairments are not fully elucidated. Herein, we aimed to explore whether BM-MSCs therapy protects against rTBI-induced long-term neurobehavioral disorders in rats via normalizing white matter integrity and gray matter microglial response. Rats were subjected to repeated mild lateral fluid percussion on day 0 and day 3. On the fourth day post-surgery, MSCs groups received MSCs (4 × 106 cells/ml/kg, intravenously) and were assessed by the radial maze, Y maze, passive avoidance tests, and modified neurological severity scores. Hematoxylin & eosin, and Luxol fast blue stainings were used to examine the histopathology and white matter thickness. At the same time, immunofluorescence staining was used to investigate the numbers of tumor necrosis factor-alpha (TNF-α)-containing microglia in gray matter. Three to nine months after neurotrauma, rats displayed sensorimotor and cognitive impairments, reduced thickness in white matter, and over-accumulation of TNF-α-containing microglia and cellular damage in gray matter. Therapy with BM-MSCs significantly attenuated the rTBI-induced sensorimotor and cognitive impairments and all their complications. Mesenchymal stem cell therapy might accelerate the recovery of sensorimotor and cognitive impairments in rats with rTBI via normalizing myelin integrity and microglia response.

中文翻译：

---

间充质干细胞可减少重复性创伤性脑损伤后的长期认知缺陷并减轻髓鞘崩解和小胶质细胞活化

骨髓间充质干细胞（BM-MSC）在治疗重复性创伤性脑损伤（rTBI）引起的长期感觉运动/认知障碍中发挥有益作用的潜在机制尚未完全阐明。在此，我们的目的是探讨 BM-MSC 疗法是否可以通过使白质完整性和灰质小胶质细胞反应正常化来预防 rTBI 诱导的大鼠长期神经行为障碍。在第0天和第3天对大鼠进行重复的轻度侧面液体敲击。术后第四天，MSCs组接受MSCs（4×106细胞/ml/kg，静脉注射），并通过径向迷宫、Y迷宫、被动回避测试和改良的神经严重程度评分进行评估。使用苏木精和曙红以及Luxol固蓝染色来检查组织病理学和白质厚度。同时，采用免疫荧光染色检测灰质中含有肿瘤坏死因子-α（TNF-α）的小胶质细胞的数量。神经创伤后三至九个月，大鼠表现出感觉运动和认知障碍、白质厚度减少、含有 TNF-α 的小胶质细胞过度积累以及灰质细胞损伤。BM-MSC 治疗显着减轻了 rTBI 引起的感觉运动和认知障碍及其所有并发症。间充质干细胞疗法可能通过使髓磷脂完整性和小胶质细胞反应正常化，加速 rTBI 大鼠感觉运动和认知障碍的恢复。