Soluble Epoxide Hydrolase in Hydrocephalus, Cerebral Edema, and Vascular Inflammation After Subarachnoid Hemorrhage.

Abstract

BACKGROUND AND PURPOSE:

Acute communicating hydrocephalus and cerebral edema are common and serious complications of subarachnoid hemorrhage (SAH), whose causes are poorly understood. Using a mouse model of SAH, we determined whether soluble epoxide hydrolase (sEH) gene deletion protects against SAH-induced hydrocephalus and edema by increasing levels of vasoprotective eicosanoids and suppressing vascular inflammation.

METHODS:

SAH was induced via endovascular puncture in wild-type and sEH knockout mice. Hydrocephalus and tissue edema were assessed by T2-weighted magnetic resonance imaging. Endothelial activation was assessed in vivo using T2*-weighted magnetic resonance imaging after intravenous administration of iron oxide particles linked to anti-vascular cell adhesion molecule-1 antibody 24 hours after SAH. Behavioral outcome was assessed at 96 hours after SAH with the open field and accelerated rotarod tests.

RESULTS:

SAH induced an acute sustained communicating hydrocephalus within 6 hours of endovascular puncture in both wild-type and sEH knockout mice. This was followed by tissue edema, which peaked at 24 hours after SAH and was limited to white matter fiber tracts. sEH knockout mice had reduced edema, less vascular cell adhesion molecule-1 uptake, and improved outcome compared with wild-type mice.

CONCLUSIONS:

Genetic deletion of sEH reduces vascular inflammation and edema and improves outcome after SAH. sEH inhibition may serve as a novel therapy for SAH.

• Authors: Dominic A Siler, Yosef A Berlow, Ayaka Kukino, Catherine M Davis, Jonathan W Nelson, Marjorie R Grafe, Hirohisa Ono, Justin S Cetas, Martin Pike, Nabil J Alkayed
• Journal: Stroke (Stroke) Vol. 46 Issue 7 Pg. 1916-22 (Jul 2015) ISSN: 1524-4628 [Electronic] United States
• PMID: 25991416 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2015 American Heart Association, Inc.

Chemical References

• Epoxide Hydrolases

Topics

• Animals
• Brain Edema (enzymology, pathology)
• Epoxide Hydrolases (deficiency)
• Inflammation (enzymology, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Subarachnoid Hemorrhage (enzymology, pathology)
• Vasculitis (enzymology, pathology)