The pathophysiological events of secondary brain injury contribute to poor outcome after traumatic brain injury (TBI). The neuroprotective effects of mesenchymal cells have been extensively studied and evidence suggests that their effects are mostly mediated through paracrine effects. Human umbilical cord perivascular cells (HUCPVCs) are mesenchymal stem cells with potential therapeutic value in TBI. In this study, we assessed the effect of HUCPVC-conditioned media (CM) in an established adult zebrafish model of TBI induced by pulsed high-intensity focused ultrasound (pHIFU). This model demonstrates similarities to mammalian outcome after TBI. Administration of HUCPVC-CM 1 h postinjury (hpi) resulted in improved outcome after pHIFU-induced TBI. Western blot and immunohistochemistry results demonstrated that the HUCPVC-CM reduced (p < 0.05) reactive astrogliosis at 24 hpi. Moreover, at 24 hpi, the HUCPVC-CM treatment resulted in reduced apoptosis in HUCPVC-CM-treated zebrafish. Behavioral analysis demonstrated improvement in locomotor activity (p < 0.05) and anxiety (p < 0.05) at 6 and 24 hpi following HUCPVC-CM treatment. Overall, HUCPVC-CM treatment improved acute outcome measures in pHIFU-injured zebrafish. Collectively, the data demonstrate a cell-free treatment approach for traumatic brain injuries.

中文翻译：

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人脐带血管周围细胞条件培养基对成年斑马鱼脑外伤模型的影响。


继发性脑损伤的病理生理事件导致创伤性脑损伤（TBI）后预后不良。间充质细胞的神经保护作用已被广泛研究，证据表明它们的作用主要是通过旁分泌作用介导的。人脐带血管周围细胞（HUCPVC）是间充质干细胞，在 TBI 中具有潜在的治疗价值。在这项研究中，我们评估了 HUCPVC 条件培养基 (CM) 在脉冲高强度聚焦超声 (pHIFU) 诱导的成年斑马鱼 TBI 模型中的作用。该模型展示了与 TBI 后哺乳动物结果的相似之处。损伤后 1 小时 (hpi) 施用 HUCPVC-CM 可改善 PHIFU 诱导的 TBI 后的预后。蛋白质印迹和免疫组织化学结果表明，HUCPVC-CM 在 24 hpi 时减少了 ( p < 0.05) 反应性星形胶质细胞增生。此外，在 24 hpi 时，HUCPVC-CM 处理导致 HUCPVC-CM 处理的斑马鱼细胞凋亡减少。行为分析表明，HUCPVC-CM 治疗后 6 小时和 24 小时后的运动活动 ( p < 0.05) 和焦虑 ( p < 0.05) 有所改善。总体而言，HUCPVC-CM 治疗改善了 PHIFU 损伤斑马鱼的急性结局指标。总的来说，这些数据证明了一种治疗创伤性脑损伤的无细胞治疗方法。