TY - CHAP
T1 - Osteopontin-Rac1 on blood-brain barrier stability following rodent neonatal hypoxia-ischemia
AU - Dixon, Brandon
AU - Malaguit, Jay
AU - Casel, Darlene
AU - Doycheva, Desislava
AU - Tang, Jiping
AU - Zhang, John H.
AU - Lekic, Tim
N1 - Funding Information:
This study was partially supported by the National Institutes of Health grant RO1 NS078755 (Dr. Zhang) and American Heart Association CRP 17380009 (Dr. Lekic).
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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).
AB - 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).
KW - Animals, Newborn
KW - Permeability
KW - Neuroprotective Agents/pharmacology
KW - Osteopontin/pharmacology
KW - Carotid Arteries/surgery
KW - Rats, Sprague-Dawley
KW - Brain Edema/metabolism
KW - Pyrimidines/pharmacology
KW - Animals
KW - Ligation
KW - Blood-Brain Barrier/drug effects
KW - Aminoquinolines/pharmacology
KW - Hypoxia-Ischemia, Brain/metabolism
KW - rac1 GTP-Binding Protein/antagonists & inhibitors
UR - https://www.scopus.com/pages/publications/84944463240
UR - https://www.scopus.com/pages/publications/84944463240#tab=citedBy
UR - https://www.mendeley.com/catalogue/be04abd7-521b-3d2f-8866-0232f43e0bdf/
U2 - 10.1007/978-3-319-18497-5_46
DO - 10.1007/978-3-319-18497-5_46
M3 - Chapter
C2 - 26463959
SN - 978-3-319-18496-8
SN - 978-3-319-36532-9
T3 - Acta Neurochirurgica, Supplementum
SP - 263
EP - 267
BT - Brain Edema XVI
PB - Springer Cham
ER -