title: Inhibition of stress fiber formation preserves blood-brain barrier after intracerebral hemorrhage in mice.
abstract: Intracerebral hemorrhage (ICH) represents the deadliest subtype of all strokes. The development of brain edema, a consequence of blood-brain barrier (BBB) disruption, is the most life-threatening event after ICH. Pathophysiological conditions activate the endothelium, one of the components of BBB, inducing rearrangement of the actin cytoskeleton. Upon activation, globular actin assembles into a filamentous actin resulting in the formation of contractile actin bundles, stress fibers. The contraction of stress fibers leads to the formation of intercellular gaps between endothelial cells increasing the permeability of BBB. In the present study, we investigated the effect of ICH on stress fiber formation in CD1 mice. We hypothesized that ICH-induced formation of stress fiber is triggered by the activation of PDGFR-β and mediated by the cortactin/RhoA/LIMK pathway. We demonstrated that ICH induces formation of stress fibers. Furthermore, we demonstrated that the inhibition of PDGFR-β and its downstream reduced the number of stress fibers, preserving BBB and resulting in the amelioration of brain edema and improvement of neurological functions in mice after ICH.
authors.affiliation: 1 Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA.|2 Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Anatol
authors.initials: A
authors.lastname: Manaenko
authors.affiliation: 1 Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA.|3 Department of Emergency Surgery, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.affiliation: 1 Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Nowrangi
authors.affiliation: 1 Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Enkhjargal
authors.initials: E
authors.lastname: Budbazar
authors.affiliation: 4 Department of Psychology, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Hartman
authors.affiliation: 5 Department of Pediatrics, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Andre
authors.initials: A
authors.lastname: Obenaus
authors.affiliation: 1 Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Pearce
authors.affiliation: 1 Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA.|6 Department of Anesthesiology, Loma Linda University, Loma Linda, CA, USA.|7 Department of Neurosurgery, Loma Linda University, Loma Linda, CA, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: 1 Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Jiping
authors.initials: J
authors.lastname: Tang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology*; D002199:Capillary Permeability / Q000502:physiology; D020300:Intracranial Hemorrhages / Q000473:pathology*; D008297:Male; D051379:Mice; D022502:Stress Fibers / Q000473:pathology*
keywords: Cortactin; LIM kinase; PDGFR-β; intracerebral hemorrhage; stress fibers