title: Necrostatin-1 ameliorates intracerebral hemorrhage-induced brain injury in mice through inhibiting RIP1/RIP3 pathway.
abstract: Necroptosis is a recently discovered programmed necrosis, regulated by receptor interacting protein kinase 1 (RIP1) and RIP3 after death signal stimulation and could be specifically inhibited by necrostatin-1. The aim of this study was to investigate the role of RIP1 and RIP3 signal pathways in a mouse model of collagenase-induced intracerebral hemorrhage (ICH) and assess the effect of necrostatin-1 on brain injury after ICH. We found that RIP1 and RIP3 proteins were abundantly expressed and increased in mice brain after ICH. Necrostatin-1 pretreatment improved neurological function and attenuated brain edema in mice after ICH. Moreover, necrostatin-1 reduced RIP1-RIP3 interaction and propidium iodide (PI) positive cell death, and further inhibited microglia activation and pro-inflammatory mediator genes [tumor necrosis factor-a (TNF-α) and interleukin-1β (IL-1β)] expression after ICH. These findings indicate that RIP1/RIP3-mediated necroptosis is an important mechanism of cell death after ICH. Through inhibiting necroptosis, necrostatin-1 plays a protective role in reducing necrotic cell death after ICH. Necrostatin-1 is a promising therapeutic agent that protects cells from necroptosis and improves functional outcome.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, People's Republic of China, neurosurgery828@gmail.com.
authors.forename: Xingfen
authors.initials: X
authors.lastname: Su
authors.forename: Handong
authors.initials: H
authors.lastname: Wang
authors.forename: Dezhi
authors.initials: D
authors.lastname: Kang
authors.forename: Jianhong
authors.initials: J
authors.lastname: Zhu
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Ke
authors.initials: K
authors.lastname: Ding
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001929:Brain Edema / Q000517:prevention & control; D001930:Brain Injuries / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000235:genetics; D020690:GTPase-Activating Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015870:Gene Expression; D007093:Imidazoles / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000187:drug effects; D009336:Necrosis; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D016207:Cytokines; D020690:GTPase-Activating Proteins; D007093:Imidazoles; D007211:Indoles; C490620:Ralbp1 protein, mouse; C507699:necrostatin-1; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C485615:Ripk3 protein, mouse