title: Chloroquine exerts neuroprotection following traumatic brain injury via suppression of inflammation and neuronal autophagic death.
abstract: 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 weight-drop device and divided randomly into three groups: sham-operated, CQ treatment and vehicle. The CQ treatment group was administered CQ (intraperitoneally, 3 mg/kg body weight) immediately following the induction of injury. The co-localization of neuron-specific nuclear protein (NeuN) and microtubule-associated protein 1 light chain 3 (LC3), was followed by immunofluorescent staining. The expression of LC3 and inflammatory cytokines was identified by western blot analysis. Wet-dry weight method was utilized to evaluate TBI-induced 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 TBI-induced cerebral edema, and the associated motor and cognitive functional deficits that occur post-injury. Following the induction of cerebral trauma, CQ treatment significantly suppressed neuronal autophagy and reduced expression levels of the inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), 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.
authors: Department of Surgery, Hebei Medical University, Shijiazhung, Hebei 050017, P.R. China.
authors: Chang-Meng
authors: CM
authors: Cui
authors: School of Basic Medical Science, Hebei United University, Tangshan, Hebei 063000, P.R. China.
authors: Jun-Ling
authors: JL
authors: Gao
authors: Department of Neurosurgery, Tangshan Workers' Hospital, Tangshan, Hebei 063000, P.R. China.
authors: Ying
authors: Y
authors: Cui
authors: Department of Neurosurgery, Tangshan Workers' Hospital, Tangshan, Hebei 063000, P.R. China.
authors: Li-Qian
authors: LQ
authors: Sun
authors: School of Basic Medical Science, Hebei United University, Tangshan, Hebei 063000, P.R. China.
authors: Yong-Chao
authors: YC
authors: Wang
authors: Department of Neurosurgery, Tangshan Workers' Hospital, Tangshan, Hebei 063000, P.R. China.
authors: Kai-Jie
authors: KJ
authors: Wang
authors: School of Basic Medical Science, Hebei United University, Tangshan, Hebei 063000, P.R. China.
authors: Ran
authors: R
authors: Li
authors: School of Basic Medical Science, Hebei United University, Tangshan, Hebei 063000, P.R. China.
authors: Yan-Xia
authors: YX
authors: Tian
authors: Department of Surgery, Hebei Medical University, Shijiazhung, Hebei 050017, P.R. China.
authors: Jian-Zhong
authors: JZ
authors: Cui
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D001929:Brain Edema / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002738:Chloroquine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D015870:Gene Expression; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D007274:Injections, Intraperitoneal; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015599:Trauma Severity Indices; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D015415:Biomarkers; D002738:Chloroquine; D053583:Interleukin-1beta; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; C526109:Anxa3 protein, rat; C546339:Rbfox3 protein, rat