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: Brandon Dixon, Jay Malaguit, Darlene Casel, Desislava Doycheva, Jiping Tang, John H Zhang, Tim Lekic
• Journal: Acta neurochirurgica. Supplement (Acta Neurochir Suppl) Vol. 121 Pg. 263-7 ( 2016) ISSN: 0065-1419 [Print] Austria
• PMID: 26463959 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Aminoquinolines
• NSC 23766
• Neuroprotective Agents
• Pyrimidines
• Osteopontin
• rac1 GTP-Binding Protein

Topics

• Aminoquinolines (pharmacology)
• Animals
• Animals, Newborn
• Blood-Brain Barrier (drug effects, metabolism)
• Brain Edema (metabolism)
• Carotid Arteries (surgery)
• Hypoxia-Ischemia, Brain (metabolism)
• Ligation
• Neuroprotective Agents (pharmacology)
• Osteopontin (pharmacology)
• Permeability
• Pyrimidines (pharmacology)
• Rats, Sprague-Dawley
• rac1 GTP-Binding Protein (antagonists & inhibitors, drug effects, metabolism)