title: Osteopontin-Rac1 on Blood-Brain Barrier Stability Following Rodent Neonatal Hypoxia-Ischemia.
abstract: Osteopontin (OPN) is a neuroprotective molecule that is upregulated following rodent neonatal hypoxic-ischemic (nHI) brain injury. Because Rac1 is a regulator of blood-brain barrier (BBB) stability, we hypothesized a role for this in OPN signaling. nHI was induced by unilateral ligation of the right carotid artery followed by hypoxia (8 % oxygen for 2 h) in P10 Sprague-Dawley rat pups. Intranasal (iN) OPN was administered at 1 h post-nHI. Groups consisted of: (1) Sham, (2) Vehicle, (3) OPN, and (4) OPN + Rac1 inhibitor (NSC23766). Evans blue dye extravasation (BBB permeability) was quantified 24 h post-nHI, and brain edema at 48 h. Increased BBB permeability and brain edema following nHI was ameliorated in the OPN treatment group. However, those rat pups receiving OPN co-treatment with the Rac1 inhibitor experienced no improvement compared with vehicle. OPN protects the BBB following nHI, and this was reversed by Rac1 inhibitor (NSC23766).
authors.affiliation: Division of Physiology and Pharmacology, School of Medicine, 11041 Campus Street, Risley Hall Rm 129, Loma Linda, CA, 92354, USA.
authors.forename: Brandon
authors.initials: B
authors.lastname: Dixon
authors.affiliation: Division of Physiology and Pharmacology, School of Medicine, 11041 Campus Street, Risley Hall Rm 129, Loma Linda, CA, 92354, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Malaguit
authors.affiliation: Department of Neonatology, School of Medicine, Loma Linda, CA, 92354, USA.
authors.forename: Darlene
authors.initials: D
authors.lastname: Casel
authors.affiliation: Division of Physiology and Pharmacology, School of Medicine, 11041 Campus Street, Risley Hall Rm 129, Loma Linda, CA, 92354, USA.
authors.forename: Desislava
authors.initials: D
authors.lastname: Doycheva
authors.affiliation: Division of Physiology and Pharmacology, School of Medicine, 11041 Campus Street, Risley Hall Rm 129, Loma Linda, CA, 92354, USA.
authors.forename: Jiping
authors.initials: J
authors.lastname: Tang
authors.affiliation: Division of Physiology and Pharmacology, School of Medicine, 11041 Campus Street, Risley Hall Rm 129, Loma Linda, CA, 92354, USA.|Department of Neurosurgery, School of Medicine, Loma Linda, CA, 92354, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: Division of Physiology and Pharmacology, School of Medicine, 11041 Campus Street, Risley Hall Rm 129, Loma Linda, CA, 92354, USA. tlekic@llu.edu.|Department of Physiology, Loma Linda University School of Medicine, 11041 Campus Street, Risley Hall Rm 129, Loma Linda, CA, 92354, USA. tlekic@llu.edu.
authors.forename: Tim
authors.initials: T
authors.lastname: Lekic
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D001929:Brain Edema / Q000378:metabolism*; D002339:Carotid Arteries / Q000601:surgery; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D008026:Ligation; D018696:Neuroprotective Agents / Q000494:pharmacology*; D053495:Osteopontin / Q000494:pharmacology*; D010539:Permeability; D011743:Pyrimidines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000634:Aminoquinolines; C487513:NSC 23766; D018696:Neuroprotective Agents; D011743:Pyrimidines; D053495:Osteopontin; D020830:rac1 GTP-Binding Protein
keywords: Experimental; Neonatal hypoxia-ischemia; Neonatal rats; Neurological dysfunction; Stroke