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褪黑素作为一种治疗性免疫调节药物对控制性皮质撞击后小鼠创伤性脑损伤的神经保护作用。

Neuroprotective Effects of Platonin, a Therapeutic Immunomodulating Medicine, on Traumatic Brain Injury in Mice after Controlled Cortical Impact.

机构信息

Department of Medical Research, Cathay General Hospital, Taipei 22174, Taiwan.

Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.

出版信息

Int J Mol Sci. 2018 Apr 6;19(4):1100. doi: 10.3390/ijms19041100.

Abstract

Traumatic brain injury (TBI) is one of the leading causes of mortality worldwide and leads to persistent cognitive, sensory, motor dysfunction, and emotional disorders. TBI-caused primary injury results in structural damage to brain tissues. Following the primary injury, secondary injuries which are accompanied by neuroinflammation, microglial activation, and additional cell death subsequently occur. Platonin, a cyanine photosensitizing dye, has been used to treat trauma, ulcers, and some types of acute inflammation. In the present study, the neuroprotective effects of platonin against TBI were explored in a controlled cortical impact (CCI) injury model in mice. Treatment with platonin (200 µg/kg) significantly reduced the neurological severity score, general locomotor activity, and anxiety-related behavior, and improved the rotarod performance of CCI-injured mice. In addition, platonin reduced lesion volumes, the expression of cleaved caspase-3, and microglial activation in TBI-insulted brains. Platonin also suppressed messenger (m)RNA levels of caspase-3, caspase-1, cyclooxygenase-2, tumor necrosis factor-α, interleukin-6, and interleukin-1β. On the other hand, free radical production after TBI was obviously attenuated in platonin-treated mice. Treatment with platonin exhibited prominent neuroprotective properties against TBI in a CCI mouse model through its anti-inflammatory, anti-apoptotic, and anti-free radical capabilities. This evidence collectively indicates that platonin may be a potential therapeutic medicine for use with TBIs.

摘要

创伤性脑损伤 (TBI) 是全球主要的死亡原因之一,导致持续的认知、感觉、运动功能障碍和情绪障碍。TBI 引起的原发性损伤导致脑组织的结构损伤。原发性损伤后,随之发生伴有神经炎症、小胶质细胞激活和其他细胞死亡的继发性损伤。血卟啉单甲醚是一种氰基光致敏染料,已被用于治疗创伤、溃疡和某些类型的急性炎症。在本研究中,研究人员在小鼠控制性皮质撞击 (CCI) 损伤模型中探索了血卟啉单甲醚对 TBI 的神经保护作用。用血卟啉单甲醚(200μg/kg)治疗可显著降低神经严重程度评分、一般运动活动和焦虑相关行为,并改善 CCI 损伤小鼠的旋转棒性能。此外,血卟啉单甲醚还降低了 TBI 损伤大脑中的病变体积、半胱天冬酶-3 的表达和小胶质细胞激活。血卟啉单甲醚还抑制了 caspase-3、caspase-1、环氧化酶-2、肿瘤坏死因子-α、白细胞介素-6 和白细胞介素-1β 的信使 (m)RNA 水平。另一方面,TBI 后自由基的产生在血卟啉单甲醚治疗的小鼠中明显减弱。在 CCI 小鼠模型中,血卟啉单甲醚通过其抗炎、抗凋亡和抗自由基能力表现出显著的神经保护作用。这些证据共同表明,血卟啉单甲醚可能是治疗 TBI 的一种潜在治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1350/5979356/74cd266d9780/ijms-19-01100-g001a.jpg

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