Abstract：Objective To observe the changes of TNF-α and NF-κB after different doses of nalmefene hydrochloride (NAL) therapy for traumatic brain injury (TBI) in an effort to identify the effect of NAL on TBI-induced inflammatory response and the possible mechanism.Methods A model of TBI in the rat was produced using the improved Feeney' s free-fall impact method.The animals were randomly divided into sham group,TBI group,TBI + large dose of NAL (ip,0.2 mg/kg) group (TBI + NAL1group),TBI + medial dose of NAL (ip,0.14 mg/kg) group (TBI + NAL2 group),TBI + small dose of NAL (ip,0.07 mg/kg) group (TBI + NAL3 group).Form of brain tissues in each group was observed and mRNA levels of TNF-α and NF-κB were measured by real-time quantitative PCR assay.Results HE staining revealed severe injury and inflammatory infiltration of brain parenchyma in TBI group ;on the contrary,the situation ameliorated in TBI + NAL1 group,TBI + NAL2 group and TBI + NAL3group,with especially obvious improvement in TBI + NAL2 group.In PCR assay,significant expression of NF-κB and TNF-α was observed at post-TBI days 1,3,5 and 7 (P ＜ 0.05),followed by great reverse after NAL therapy (P ＜ 0.05),particularly in TBI + NAL2 group.Conclusions NAL can reduce the inflammation response to TBI and promote post-injury recovery.Moreover,there exists a NAL concentration window.
ZHANG Yong,GAO Pei-long,CHU Pei et al. Impact of nalmefene hydrochloride on inflammatory reaction in rats with traumatic brain injury[J]. CHINESE JOURNAL OF TRAUMA, 2013, 29(10): 991-995.
［2］Nealey KA, Smith AW, Davis SM, et al. kappa-opioid receptors are implicated in the increased potency of intra-accumbens nalmefene in ethanol-dependent rats. Neuropharmacology, 2011,61(1-2):35-42.
［5］Chen CC, Hung TH, Wang YH, et al. Wogonin improves histological and functional outcomes, and reduces activation of TLR4/NF-kappaB signaling after experimental traumatic brain injury. PLoS One, 2012, 7(1):e30294.
［6］Wei J, Pan X, Pei Z, et al. The beta-lactam antibiotic, ceftriaxone, provides neuroprotective potential via anti-excitotoxicity and anti-inflammation response in a rat model of traumatic brain injury. J Trauma Acute Care Surg, 2012, 73(3): 654-660.
［11］Pasaoglu H,Inci Karakücük E,Kurtsoy A,et al.Endogenous neuropeptides in patients with acute traumatic head injury, Ⅰ: cerebrospinal fluid beta-endorphin levels are increased within 24 hours following the trauma.Neuropeptides,1996,30(1):47-51.
［16］Osborn MD, Lowery JJ, Skorput AG, et al. In vivo characterization of the opioid antagonist nalmefene in mice. Life Sci, 2010, 86(15-16):624-630.
［17］Spanagel R, Vengeliene V. New pharmacological treatment strategies for relapse prevention. Curr Topice in behavioral neurosciences, 2013, 13:583-609.
［18］Phan NQ, Bernhard JD, Luger TA, et al. Antipruritic treatment with systemic mu-opioid receptor antagonists: a review. J Am Acad Dermatol, 2010, 63(4):680-688.
［19］Atkins CM, Kang Y, Furones C, et al. Postinjury treatment with rolipram increases hemorrhage after traumatic brain injury. J Neurosci Res, 2012, 90(9):1861-1871.
［20］Lu J, Goh SJ, Tng PY, et al. Systemic inflammatory response following acute traumatic brain injury. Front Biosci (Landmark Ed), 2009, 14:3795-3813.
