title: PARP inhibition attenuates early brain injury through NF-κB/MMP-9 pathway in a rat model of subarachnoid hemorrhage.
abstract: Poly (ADP-ribose) polymerases (PARPs) play an important role in a range of neurological disorders, however, the role of PARP in early brain injury after subarachnoid hemorrhage (SAH) remains unclear. This study was designed to explore the role and the potential mechanisms of PARP in early brain injury after SAH. Eighty-nine male SD rats were randomly divided into the Sham group, SAH+Vehicle group and SAH+PARP inhibitor (PJ34) group. An endovascular perforation model was used to induce SAH in rats. PJ34 (10mg/kg) or vehicle (0.9% NaCl) was intraperitoneally administered at 5min and 8h after SAH induction. Mortality, SAH grades, neurological function, evans blue extravasation, brain edema, immunofluorescence staining and western blotting were performed. PJ34 reduced BBB permeability and brain edema, improved neurological function and attenuated neuronal cell death in the rat model of SAH. Moreover, PJ34 inhibited the nuclear translocation of NF-κB, decreased the expression of the proinflammatory cytokines IL-1ß, IL-6 and TNF-α, reduced the expression of MMP-9, prevented the degradation of tight junction proteins, and decreased microglia activation. These data indicated that PARP inhibition through PJ34 might be an important therapeutic drug for SAH.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, China; Department of Neurosurgery, The Punan Hospital of Pudong New District, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, China.
authors.forename: Jian-Ru
authors.initials: JR
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, China.
authors.forename: Hang-Zhe
authors.initials: HZ
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, China.
authors.forename: Yu-Cong
authors.initials: YC
authors.lastname: Peng
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, China.
authors.forename: Lin-Feng
authors.initials: LF
authors.lastname: Fan
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yan
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, China. Electronic address: d-chengao@zju.edu.cn.
authors.forename: Gao
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D062507:Claudin-5 / Q000378:metabolism; D004195:Disease Models, Animal; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D062793:Occludin / Q000378:metabolism; D010616:Phenanthrenes / Q000008:administration & dosage; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000008:administration & dosage; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013345:Subarachnoid Hemorrhage / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D062507:Claudin-5; C491510:Cldn5 protein, rat; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D015850:Interleukin-6; C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D016328:NF-kappa B; D062793:Occludin; C568987:Ocln protein, rat; D010616:Phenanthrenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D011065:Poly(ADP-ribose) Polymerases; D020780:Matrix Metalloproteinase 9
keywords: Early brain injury; MMP-9; NF-κB; PARP; PJ34; Subarachnoid hemorrhage