title: Posttraumatic administration of luteolin protects mice from traumatic brain injury: implication of autophagy and inflammation.
abstract: Secondary brain insult induced by traumatic brain injury (TBI), including excitotoxicity, oxidative stress, inflammatory response, and neuronal degeneration, is sensitive to therapeutic interventions; therefore, searching for neuroprotective agents represents a promising therapeutic strategy for TBI treatment. Luteolin, a member of the flavonoid family, has recently been proven to modulate autophagy. However, whether it activates autophagy after TBI thereby alleviating the secondary insult is not yet understood. Here, we aimed to evaluate the neuroprotection of luteolin against TBI and the potential role of autophagy where it is involved. For this purpose, mice were randomly divided into four groups and then subjected to TBI. The treatment mice received luteolin at a dose of 30mg/kg 30min post-TBI based on our previous study. We employed western blot, immunofluorescence and quantitative real-time PCR to determine autophagy process and inflammatory response among different groups. Autophagy was found to be enhanced after luteolin treatment according to the expressions of autophagic markers. Furthermore, luteolin decreased nuclear accumulation of p65 induced by TBI, indicating attenuation of inflammation. In line with these observations, luteolin decreased mRNA and protein expressions of pro-inflammatory factors IL-1b and TNF-a. At last, luteolin reduced neuronal degeneration, and alleviated brain edema and blood-brain barrier (BBB) disruption. In conclusion, these results implied that luteolin protected mice brain from traumatic brain injury by inhibiting inflammatory response, and luteolin-induced autophagy might play a pivotal role in its neuroprotection.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China. Electronic address: njhdwang@hotmail.com.
authors.forename: Handong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Ding
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Jin
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Southern Medical University (Guangzhou), Nanjing, Jiangsu Province, China.
authors.forename: Wuting
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D053583:Interleukin-1beta / Q000378:metabolism; D047311:Luteolin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D015213:Neuroimmunomodulation / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D047311:Luteolin
keywords: Autophagy; Inflammation; Luteolin; Neuroprotection; Traumatic brain injury