Department of Medical Research, Cathay General Hospital, Taipei 22174, Taiwan.
Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
Int J Mol Sci. 2018 Apr 6;19(4):1100. doi: 10.3390/ijms19041100.
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.
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。