Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, India.
Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, India.
J Surg Res. 2014 May 1;188(1):268-79. doi: 10.1016/j.jss.2013.12.028. Epub 2014 Jan 3.
Traumatic head injury is turning out to be a major cause of disability and death. Nitric oxide (NO), an intercellular messenger plays a crucial role in the pathophysiology of several neurologic disorders. Therefore, the present study was designed to investigate the effects of rutin, a well-known flavonoid against cognitive deficits and neuroinflammation associated with traumatic head injury and the probable role of NO pathway in this effect.
Wistar rats were exposed to head trauma using weight drop method and kept for a postsurgical rehabilitation period of 2 wk. Later, animals were administered with rutin (20, 40, and 80 mg/kg; per oral) alone and in combination with NO modulators such as N(G)-nitro-L-arginine methyl ester and L-arginine, daily for another 2 wk.
Head injury caused impaired spatial navigation in Morris water maze test and poor retention in elevated plus maze task. Furthermore, there was a significant rise in acetylcholinesterase activity, oxidative stress, neuroinflammation (tumor necrosis factor α), and neuronal apoptosis (caspase-3) in both cortex and hippocampal regions of traumatized rat brain. Rutin significantly attenuated these behavioral, biochemical, and molecular alterations associated with head trauma. Furthermore, pretreatment of N(G)-nitro-L-arginine methyl ester (10 mg/kg, intraperitoneally), a nonspecific nitric oxide synthase inhibitor, with subeffective dose of rutin (40 mg/kg) potentiated the protective effects; however, pretreatment of L-arginine (100 mg/kg; intraperitoneally), an NO donor, reversed the effects of rutin.
The present study suggests that NO modulation could possibly be involved in the neuroprotective effects of rutin against head trauma-induced cognitive deficits, neuroinflammation, and apoptotic signaling cascade.
创伤性颅脑损伤正在成为残疾和死亡的主要原因。一氧化氮（NO）作为一种细胞间信使，在几种神经疾病的病理生理学中起着至关重要的作用。因此，本研究旨在探讨芦丁（一种著名的黄酮类化合物）对创伤性颅脑损伤相关认知障碍和神经炎症的影响，以及 NO 通路在这种作用中的可能作用。
Wistar 大鼠采用重物坠落法致颅脑损伤，并进行术后康复 2 周。随后，动物单独给予芦丁（20、40 和 80mg/kg；口服），并与 NO 调节剂如 N(G)-硝基-L-精氨酸甲酯和 L-精氨酸联合给药，每天 1 次，共 2 周。
颅脑损伤导致 Morris 水迷宫测试中空间导航受损和高架十字迷宫任务中保留时间差。此外，创伤性大鼠大脑皮质和海马区乙酰胆碱酯酶活性、氧化应激、神经炎症（肿瘤坏死因子-α）和神经元凋亡（caspase-3）显著升高。芦丁显著减轻了这些与颅脑损伤相关的行为、生化和分子改变。此外，预先给予非特异性一氧化氮合酶抑制剂 N(G)-硝基-L-精氨酸甲酯（10mg/kg，腹腔内注射）与芦丁（40mg/kg）亚效剂量联合预处理增强了保护作用；然而，预先给予一氧化氮供体 L-精氨酸（100mg/kg；腹腔内注射）则逆转了芦丁的作用。
本研究表明，NO 调节可能参与了芦丁对颅脑损伤引起的认知障碍、神经炎症和凋亡信号级联的神经保护作用。
