title: Tert-butylhydroquinone Ameliorates Early Brain Injury After Experimental Subarachnoid Hemorrhage in Mice by Enhancing Nrf2-Independent Autophagy.
abstract: Evidence has shown that the activation of the autophagy pathway after experimental subarachnoid hemorrhage (SAH) protects against neuronal damage. Tert-butylhydroquinone (tBHQ), a commonly used nuclear factor erythroid 2-related factor 2 (Nrf2) activator, was found to significantly enhance autophagy activation. The aim of this study was to explore the effect of tBHQ treatment on early stage brain injury at 24 h after SAH. The results showed that tBHQ treatment failed to stimulate an effective anti-oxidative effect at 24 h after the SAH operation, but succeeded in ameliorating early brain injury, including alleviated brain edema, BBB disruption, neuronal degeneration and neurological deficits. Further exploration found that tBHQ treatment significantly increased the expression of Beclin-1 and the ratio of microtubule-associated protein 1 light chain 3 (LC3)-II to LC3-I, suggesting that autophagy was enhanced after tBHQ treatment. Moreover, tBHQ treatment restored Bcl-2 and Bax expression and reduced caspase-3 cleavage, suggesting the protective effect of tBHQ treatment in ameliorating brain injury after SAH. Furthermore, tBHQ enhanced autophagy activation, decreased neuronal degeneration and improved the neurological score after SAH in Nrf2-deficient mice. Taken together, these findings suggest that tBHQ treatment exerts neuro-protective effects against EBI following SAH by enhancing Nrf2-independent autophagy. Therefore, tBHQ is a promising therapeutic agent against EBI following SAH.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Kang-jian
authors.initials: KJ
authors.lastname: Sun
authors.forename: Han-Dong
authors.initials: HD
authors.lastname: Wang
authors.forename: Meng-Liang
authors.initials: ML
authors.lastname: Zhou
authors.forename: Ke
authors.initials: K
authors.lastname: Ding
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Lu
authors.forename: Wu-Ting
authors.initials: WT
authors.lastname: Wei
authors.forename: Chun-Xi
authors.initials: CX
authors.lastname: Wang
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D001812:Blood-Brain Barrier; D001930:Brain Injuries / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D006873:Hydroquinones / Q000494:pharmacology*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D013345:Subarachnoid Hemorrhage / Q000150:complications*
chemical_list: D006873:Hydroquinones; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; C018855:2-tert-butylhydroquinone