title: The action of thrombin in intracerebral hemorrhage induced brain damage is mediated via PKCα/PKCδ signaling.
abstract: The present study investigates the role of protein kinase C alpha/delta (PKCα/PKCδ) in brain injury induced by intracerebral hemorrhage (ICH) by utilizing a rat model that received intracerebral injections of autologous blood and thrombin (TM). The activation and expression of PKC and PKCδ were analyzed by Western blot and immunohistochemistry. A PKC inhibitor, dihydrochloride (H7), was administrated intraperitoneally after injury to evaluate the effect of inhibition of PKC on ICH and TM induced brain damage. Our data indicate that both ICH and TM increased the expression of PKCα/PKCδ in the brain tissue, and PKCα expression peaked at 6h, while PKCδ expression reached its maximum value at 72h post-injury. Administration of H7 significantly reduced the inflammatory cells infiltrate, permeability of brain-blood barrier (BBB), brain edema, and neuronal death. We conclude that both PKCα and PKCδ play important roles in ICH and TM-induced brain injury, and dihydrochloride (H7) can attenuate brain damage after ICH.
authors.affiliation: Department of Neurology, Nanjing Brain Hospital, Nanjing Medical University, No. 264 Guangzhou Road, Nanjing 210029, PR China.
authors.forename: Gui-Yun
authors.initials: GY
authors.lastname: Cui
authors.forename: Xiu-Ming
authors.initials: XM
authors.lastname: Gao
authors.forename: Su-Hua
authors.initials: SH
authors.lastname: Qi
authors.forename: Aleena
authors.initials: A
authors.lastname: Gillani
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.forename: Xia
authors.initials: X
authors.lastname: Shen
authors.forename: Ying-Dong
authors.initials: YD
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001925:Brain Damage, Chronic / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*; D002543:Cerebral Hemorrhage / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D008297:Male; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors / Q000502:physiology*; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D013917:Thrombin / Q000378:metabolism / Q000633:toxicity*
chemical_list: D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D013917:Thrombin