• Anil Kumar, Puneet Rinwa, and Hitesh Dhar.
• Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, India. Electronic address: kumaruips@rediffmail.com.
• J. Surg. Res. 2014 May 1;188(1):268-79.

BackgroundTraumatic 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.Materials And MethodsWistar 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.ResultsHead 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.ConclusionsThe 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.Copyright © 2014 Elsevier Inc. All rights reserved.

47 keywords...

hide…