title: LPS Pretreatment Provides Neuroprotective Roles in Rats with Subarachnoid Hemorrhage by Downregulating MMP9 and Caspase3 Associated with TLR4 Signaling Activation.
abstract: Subarachnoid hemorrhage (SAH), as a severe brain disease, has high morbidity and mortality. SAH usually induced neurological dysfunction or death and the treatment is far from satisfaction. Here, we investigated the effect of low dose of LPS pretreatment and underlying molecular mechanism in rat SAH model. Firstly, SAH model was induced by prechiasmal cistern injection method (SAH1) and common carotid artery-prechiasmal cistern shunt method (SAH2), respectively, to select the more suitable SAH model. At 6, 12, 24, 48, and 72 h after SAH, brain injury including neurological dysfunction, blood-brain barrier disruption, brain edema, and cell apoptosis were detected. And the expression of MMP9, HMGB1/TLR4, and caspase3 in cortex were also explored. Then, SB-3CT, an inhibitor of MMP9, was administrated to investigate the exact function of MMP9 in the brain injury at 24 h after SAH. Moreover, low dose of LPS was used to verify whether it had nerve protection after SAH and the mechanism involving in MMP9 and caspase 3 was investigated. Our results showed SAH1 seems to be the most suitable SAH model. In addition, MMP9 activated by HMGB1/TLR4 may promote or aggravate brain injury, while inhibiting MMP9 via SB-3CT exerted a neuroprotective effect. Moreover, LPS improved the neurological dysfunction, reduced Evans blue extravasation and brain edema, and inhibited cell apoptosis of cortex in rats with brain injury induced by SAH. Importantly, LPS pretreatment increased the expression level of TLR4, and decreased the level of MMP9 and caspase3. Therefore, the present study revealed that low dose of LPS pretreatment could provide neuroprotective effects on brain injury caused by SAH via downregulating MMP9 and caspase3 and activating TLR4 signal pathway.
authors.affiliation: Institute of Neurological Disease, and Department of Neurosurgery, Translational Neuroscience Center, the state key laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Ting-Hua
authors.initials: TH
authors.lastname: Wang
authors.affiliation: Institute of Neurological Disease, and Department of Neurosurgery, Translational Neuroscience Center, the state key laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Liu-Lin
authors.initials: LL
authors.lastname: Xiong
authors.affiliation: Institute of Neurological Disease, and Department of Neurosurgery, Translational Neuroscience Center, the state key laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Shuai-Fen
authors.initials: SF
authors.lastname: Yang
authors.affiliation: Institute of Neurological Disease, and Department of Neurosurgery, Translational Neuroscience Center, the state key laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: You
authors.affiliation: Institute of Neurological Disease, and Department of Neurosurgery, Translational Neuroscience Center, the state key laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Qing-Jie
authors.initials: QJ
authors.lastname: Xia
authors.affiliation: Institute of Neurological Disease, and Department of Neurosurgery, Translational Neuroscience Center, the state key laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Animal Zoology Department, Institute of Neuroscience, Kunming medical University, Kunming, 650000, China.
authors.forename: Piao
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Yunnan Key Laboratory of Stem Cells and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, 650000, China. wsf66@hotmail.com.
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Wang
authors.affiliation: Institute of Neurological Disease, and Department of Neurosurgery, Translational Neuroscience Center, the state key laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China. liujiaaixuexi@126.com.|Animal Zoology Department, Institute of Neuroscience, Kunming medical University, Kunming, 650000, China. liujiaaixuexi@126.com.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013345:Subarachnoid Hemorrhage / Q000378:metabolism* / Q000517:prevention & control; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D053148:Caspase 3; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
keywords: Early brain injury; HMGB1; LPS; MMP9; Subarachnoid hemorrhage; TLR4