title: Genetic elimination of Nrf2 aggravates secondary complications except for vasospasm after experimental subarachnoid hemorrhage in mice.
abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key endogenous protective regulator in the body. This study aimed to explore the role of Nrf2 in subarachnoid hemorrhage (SAH)-induced secondary complications. Wild type (WT) and Nrf2 knockout (KO) mice were subjected to experimental SAH by injecting fresh autologous blood into pre-chiasmatic cistern. The absence of Nrf2 function in mice resulted in exacerbated brain injury with increased brain edema, blood-brain barrier (BBB) disruption, neural apoptosis, and severe neurological deficits at 24h after SAH. Moreover, cerebral vasospasm was severe at 24h after SAH, but not significantly different between WT and Nrf2 KO mice after SAH. Meanwhile, Molondialdehyde (MDA) was increased and GSH/GSSG ratio was decreased in Nrf2 KO mice after SAH. Furthermore, higher expression of TNF-α and IL-1β was also found after SAH in Nrf2 KO mice. In conclusion, our results revealed that Nrf2 plays an important role in attenuating SAH-induced secondary complications by regulating excessive oxidative stress and inflammatory response.
authors.affiliation: Department of Neurosurgery, Jinling Hospital Affiliated to Nanjing University School of Medicine, Nanjing, Jiangsu 210089, PR China; Department of Neurosurgery, Jinling Hospital, Neurosurgical Institution of People's Liberation Army of China, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Jinling Hospital, Neurosurgical Institution of People's Liberation Army of China, PR China. Electronic address: njhdwang@hotmail.com.
authors.forename: Handong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Jinling Hospital Affiliated to Nanjing University School of Medicine, Nanjing, Jiangsu 210089, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Neurosurgery, Jinling Hospital, Neurosurgical Institution of People's Liberation Army of China, PR China.
authors.forename: Mengliang
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Jinling Hospital, Neurosurgical Institution of People's Liberation Army of China, PR China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Jinling Hospital, Neurosurgical Institution of People's Liberation Army of China, PR China.
authors.forename: Xiangshen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, Neurosurgical Institution of People's Liberation Army of China, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Ding
authors.affiliation: Department of Neurosurgery, Jinling Hospital, Neurosurgical Institution of People's Liberation Army of China, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Neurosurgery, Jinling Hospital Affiliated to Nanjing University School of Medicine, Nanjing, Jiangsu 210089, PR China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, Jinling Hospital Affiliated to Nanjing University School of Medicine, Nanjing, Jiangsu 210089, PR China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xu
authors.affiliation: Neurosurgery Department of Southern Medical University, Guangzhou, Guangdong 510515, PR China.
authors.forename: Wuting
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000473:pathology; D001929:Brain Edema / Q000209:etiology; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D053583:Interleukin-1beta / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000172:deficiency*; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D020301:Vasospasm, Intracranial / Q000175:diagnosis / Q000209:etiology*
chemical_list: D053583:Interleukin-1beta; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D005978:Glutathione; D019803:Glutathione Disulfide
keywords: BBB disruption; Brain edema; Cerebral vasospasm; Inflammatory response; Nrf2; Oxidative stress; Subarachnoid hemorrhage