title: Protective actions of PJ34, a poly(ADP-ribose)polymerase inhibitor, on the blood-brain barrier after traumatic brain injury in mice.
abstract: Poly(ADP-ribose) polymerase (PARP) is activated by oxidative stress and plays an important role in traumatic brain injury (TBI). The objective of this study was to investigate whether PARP activation participated in the blood-brain barrier (BBB) disruption and edema formation in a mouse model of controlled cortical impact (CCI). N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide (PJ34) (10 mg/kg), a selective PARP inhibitor, was administered intraperitoneally at 5 min and 8 h after experimental CCI. After 6 h and 24 h of CCI, the permeability of the cortical BBB was determined after Evans Blue administration. The water content of the brain was also measured. Treatment with PJ34 markedly attenuated the permeability of the BBB and decreased the brain edema at 6 h and 24 h after CCI. Our data showed the up-regulation of nuclear factor-κB in cytosolic fractions and nuclear fractions in the injured cortex, and these changes were reversed by PJ34. Moreover, PJ34 significantly lessened the activities of myeloperoxidase and the levels of matrix metalloproteinase-9, enhanced the levels of occludin, laminin, collagen IV and integrin β1, reduced neurological deficits, decreased the contusion volume, and attenuated the necrotic and apoptotic neuronal cell death. These data suggest the protective effects of PJ34 on BBB integrity and cell death during acute TBI.
authors: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors: X
authors: X
authors: Tao
authors: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors: X
authors: X
authors: Chen
authors: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors: S
authors: S
authors: Hao
authors: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors: Z
authors: Z
authors: Hou
authors: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors: T
authors: T
authors: Lu
authors: Department of Neuropharmacology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China. Electronic address: sunming999@yahoo.com.
authors: M
authors: M
authors: Sun
authors: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; Department of Neurotrauma, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China; Nerve Injury and Repair Center of Beijing Institute for Brain Disorders, Beijing 100050, China; Department of Neurotrauma, General Hospital of Armed Police Forces, Beijing 100039, China; China National Clinical Research Center for Neurological Diseases, Beijing 100050, China; Beijing Key Laboratory of Central Nervous System Injury, Beijing 100050, China. Electronic address: liubaiyun1963@163.com.
authors: B
authors: B
authors: Liu
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D062793:Occludin / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011897:Random Allocation
chemical_list: C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D016328:NF-kappa B; D018696:Neuroprotective Agents; D062793:Occludin; C568986:Ocln protein, mouse; D010616:Phenanthrenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: NF-κB; blood–brain barrier; brain edema; poly(ADP-ribose) polymerase; traumatic brain injury