title: DL-3-n-Butylphthalide (NBP) Provides Neuroprotection in the Mice Models After Traumatic Brain Injury via Nrf2-ARE Signaling Pathway.
abstract: The present study was aimed to evaluate the neuroprotective effects of NBP in the mice models of TBI, as well as the possible role of Nrf2-ARE pathways in the assumptive neuroprotection. In mice,a modified Marmarou's weight-drop model was employed to induce TBI. ICR mice were randomly assigned to four experimental groups: sham, TBI, TBI+vehicle(V) and TBI+NBP. NBP (100 mg/kg) was administered via an intraperitoneal (i.p.) injection at 1 h following TBI. The administration of NBP significantly ameliorated the effects of the brain injury, including neurological deficits, brain water content, and cortical neuronal apoptosis. Furthermore, the level of malondialdehyde and the activity of superoxide dismutase (SOD) paired with glutathione peroxidase (GPx) were restored in the NBP treatment group. NBP promoted the translocation of Nrf2 protein from the cytoplasm to the nucleus markedly, increased the expressions of Nrf2-ARE pathway-related downstream factors, including hemeoxygenase-1(HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1), and prevented the decline of antioxidant enzyme activities, including SOD and GPx. NBP enhanced the translocation of Nrf2 to the nucleus from the cytoplasm,verified by a western blot, immunofluorescence. Additionally, it upregulated the expression of the Nrf2 downstream factors such as HO-1 and NQO1 were also confirmed via a western blot and real-time quantitative polymerase chain reaction. In conclusion, NBP administration may increase the activities of antioxidant enzymes and attenuate brain injury in a TBI model, potentially via the mediation of the Nrf2-ARE pathway.
authors.affiliation: Department of Neurosurgery, School of Medicine, Jinling Hospital, Southern Medical University (Guangzhou), 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, People's Republic of China.|Department of Neurosurgery, Shenzhen Longgang Central Hospital, 6082 Longgangdadao Road, Shenzhen, 518116, Guangdong, People's Republic of China.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, School of Medicine, Jinling Hospital, Southern Medical University (Guangzhou), 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, People's Republic of China. njhdwang@hotmail.com.
authors.forename: Handong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Shenzhen Longgang Central Hospital, 6082 Longgangdadao Road, Shenzhen, 518116, Guangdong, People's Republic of China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Neurosurgery, School of Medicine, Jinling Hospital, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, People's Republic of China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, School of Medicine, Jinling Hospital, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, People's Republic of China.
authors.forename: Mengliang
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, School of Medicine, Jinling Hospital, Southern Medical University (Guangzhou), 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ding
authors.affiliation: Department of Neurosurgery, School of Medicine, Jinling Hospital, Southern Medical University (Guangzhou), 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, People's Republic of China.
authors.forename: Youqing
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, School of Medicine, Jinling Hospital, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, School of Medicine, Jinling Hospital, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Ding
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000494:pharmacology / Q000627:therapeutic use*; D000070642:Brain Injuries, Traumatic / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D001572:Benzofurans; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495636:Nfe2l2 protein, mouse; C027125:3-n-butylphthalide
keywords: DL-3-n-Butylphthalide; Mice model; Neuroprotection; Nrf2-ARE signaling pathway; Traumatic brain injury