The antimalarial drug, chloroquine (CQ), has been reported as an autophagy inhibitor in a variety of disorders, including Alzheimer's disease and brain ischemia. To the best of our knowledge, no studies to date have examined the potential for CQ to provide neuroprotection in animal
models of traumatic brain injury (TBI). The aim of this study was to investigate the neuroprotective actions of CQ in TBI and to determine the mechanisms underlying this effect. Rats were immediately subjected to a diffuse cortical impact injury caused by a modified weightdrop device and divided
randomly into three groups: shamoperated, CQ treatment and vehicle. The CQ treatment group was administered CQ (intraperitoneally, 3 mg/kg body weight) immediately following the induction of injury. The colocalization of neuronspecific nuclear protein (NeuN) and microtubuleassociated
protein 1 light chain 3 (LC3), was followed by immunofluorescent staining. The expression of LC3 and inflammatory cytokines was identified by western blot analysis. Wetdry weight method was utilized to evaluate TBIinduced brain edema. Motor function was evaluated using the Neurological Severity
Score (NSS) scale and the Morris water maze was employed to assess spatial learning ability. This study demonstrated that the administration of CQ attenuates TBIinduced cerebral edema, and the associated motor and cognitive functional deficits that occur postinjury. Following the induction
of cerebral trauma, CQ treatment significantly suppressed neuronal autophagy and reduced expression levels of the inflammatory cytokines, interleukin1β (IL1β) and tumor necrosis factorα (TNFα), in the rat hippocampus. Our results have provided in vivo evidence that
CQ may exert neuroprotective effects following TBI, in attenuating brain edema and improving neurological functioning, by reducing the damaging consequences of neuronal autophagy and cerebral inflammation.
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Document Type: Research Article
Department of Surgery, Hebei Medical University, Shijiazhung, Hebei 050017, P.R. China
School of Basic Medical Science, Hebei United University, Tangshan, Hebei 063000, P.R. China
Department of Neurosurgery, Tangshan Workers' Hospital, Tangshan, Hebei 063000, P.R. China
Publication date: August 1, 2015
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Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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