title: Protection of the brain following cerebral ischemia through the attenuation of PARP-1-induced neurovascular unit damage in rats.
abstract: Cerebral ischemia is a major health crisis throughout the world, and the currently available thrombolytic therapy is unsatisfactory. Cell death following cerebral ischemia is mediated by a complex pathophysiological interaction of various mechanisms. During an ischemic insult, not only neurons but all of the components of the neurovascular unit, such as glia, endothelia, pericytes and basal membranes, are destroyed. Previous studies have shown that excessive stimulation of poly (ADP-ribose) polymerase (PARP-1) is crucial for cerebral injury after ischemic insult, which is an important cause of cell death in all cell types within the neurovascular unit. To investigate whether PARP-1 plays an important role in protecting the neurovascular unit following cerebral ischemia, we evaluated neurobehavioral deficits, PARP-1 activity, blood brain barrier (BBB) disruption and neurovascular unit deficits using Western blot analysis, TTC staining and electron microscopy in an MCAO rat model. The results revealed that PARP-1 enzymatic activity was dramatically increased after ischemia. Inhibition of PARP-1 significantly reduced the extent of both cerebral infarction and edema, improved neurological scores, and attenuated the damage to the neurovascular unit in cerebral ischemia. Collectively, these findings demonstrate that the down-regulation of PARP-1 activity contributes to reducing post-ischemic brain damage via protection of the neurovascular unit.
authors.affiliation: Department of Neurology, Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, Shandong, PR China.
authors.forename: Ruixue
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Shandong Provincial Hospital, Shandong University, 324 Jing Wu Wei Qi Road, Jinan 250021, Shandong, PR China.
authors.forename: Shi
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Neurology, Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, Shandong, PR China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Neurology, Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, Shandong, PR China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurology, Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, Shandong, PR China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Neurology, Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, Shandong, PR China.
authors.forename: Heng
authors.initials: H
authors.lastname: Chi
authors.affiliation: Department of Neurology, Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, Shandong, PR China.
authors.forename: Meijia
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, Shandong, PR China. Electronic address: tjiyou@yahoo.com.
authors.forename: Jiyou
authors.initials: J
authors.lastname: Tang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001812:Blood-Brain Barrier / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D008297:Male; D046529:Microscopy, Electron, Transmission; D009186:Myelin Sheath / Q000473:pathology / Q000648:ultrastructure; D009422:Nervous System Diseases / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D009457:Neuroglia / Q000473:pathology / Q000648:ultrastructure; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000473:pathology / Q000648:ultrastructure; D013997:Time Factors; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases
keywords: Cerebral ischemia; Neurovascular unit; Poly(ADP-ribose) polymerase