title: Soluble Epoxide Hydrolase in Hydrocephalus, Cerebral Edema, and Vascular Inflammation After Subarachnoid Hemorrhage.
abstract: OBJECTIVE
  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.affiliation: From the Department of Anesthesiology and Perioperative Medicine, The Knight Cardiovascular Institute (D.A.S., C.M.D., J.W.N., M.R.G., N.J.A.), Department of Neurological Surgery (D.A.S., J.S.C.), Advanced Imaging Research Center (Y.A.B., A.K., M.P.), Oregon Health and Science University, Portland; Department of Neurosurgery, Nishijima Hospital, Numazu City, Sizuoka, Japan (H.O.); and Portland VA Medical Center, OR (J.S.C.).
authors.forename: Dominic A
authors.initials: DA
authors.lastname: Siler
authors.affiliation: From the Department of Anesthesiology and Perioperative Medicine, The Knight Cardiovascular Institute (D.A.S., C.M.D., J.W.N., M.R.G., N.J.A.), Department of Neurological Surgery (D.A.S., J.S.C.), Advanced Imaging Research Center (Y.A.B., A.K., M.P.), Oregon Health and Science University, Portland; Department of Neurosurgery, Nishijima Hospital, Numazu City, Sizuoka, Japan (H.O.); and Portland VA Medical Center, OR (J.S.C.).
authors.forename: Yosef A
authors.initials: YA
authors.lastname: Berlow
authors.affiliation: From the Department of Anesthesiology and Perioperative Medicine, The Knight Cardiovascular Institute (D.A.S., C.M.D., J.W.N., M.R.G., N.J.A.), Department of Neurological Surgery (D.A.S., J.S.C.), Advanced Imaging Research Center (Y.A.B., A.K., M.P.), Oregon Health and Science University, Portland; Department of Neurosurgery, Nishijima Hospital, Numazu City, Sizuoka, Japan (H.O.); and Portland VA Medical Center, OR (J.S.C.).
authors.forename: Ayaka
authors.initials: A
authors.lastname: Kukino
authors.affiliation: From the Department of Anesthesiology and Perioperative Medicine, The Knight Cardiovascular Institute (D.A.S., C.M.D., J.W.N., M.R.G., N.J.A.), Department of Neurological Surgery (D.A.S., J.S.C.), Advanced Imaging Research Center (Y.A.B., A.K., M.P.), Oregon Health and Science University, Portland; Department of Neurosurgery, Nishijima Hospital, Numazu City, Sizuoka, Japan (H.O.); and Portland VA Medical Center, OR (J.S.C.).
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Davis
authors.affiliation: From the Department of Anesthesiology and Perioperative Medicine, The Knight Cardiovascular Institute (D.A.S., C.M.D., J.W.N., M.R.G., N.J.A.), Department of Neurological Surgery (D.A.S., J.S.C.), Advanced Imaging Research Center (Y.A.B., A.K., M.P.), Oregon Health and Science University, Portland; Department of Neurosurgery, Nishijima Hospital, Numazu City, Sizuoka, Japan (H.O.); and Portland VA Medical Center, OR (J.S.C.).
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Nelson
authors.affiliation: From the Department of Anesthesiology and Perioperative Medicine, The Knight Cardiovascular Institute (D.A.S., C.M.D., J.W.N., M.R.G., N.J.A.), Department of Neurological Surgery (D.A.S., J.S.C.), Advanced Imaging Research Center (Y.A.B., A.K., M.P.), Oregon Health and Science University, Portland; Department of Neurosurgery, Nishijima Hospital, Numazu City, Sizuoka, Japan (H.O.); and Portland VA Medical Center, OR (J.S.C.).
authors.forename: Marjorie R
authors.initials: MR
authors.lastname: Grafe
authors.affiliation: From the Department of Anesthesiology and Perioperative Medicine, The Knight Cardiovascular Institute (D.A.S., C.M.D., J.W.N., M.R.G., N.J.A.), Department of Neurological Surgery (D.A.S., J.S.C.), Advanced Imaging Research Center (Y.A.B., A.K., M.P.), Oregon Health and Science University, Portland; Department of Neurosurgery, Nishijima Hospital, Numazu City, Sizuoka, Japan (H.O.); and Portland VA Medical Center, OR (J.S.C.).
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Ono
authors.affiliation: From the Department of Anesthesiology and Perioperative Medicine, The Knight Cardiovascular Institute (D.A.S., C.M.D., J.W.N., M.R.G., N.J.A.), Department of Neurological Surgery (D.A.S., J.S.C.), Advanced Imaging Research Center (Y.A.B., A.K., M.P.), Oregon Health and Science University, Portland; Department of Neurosurgery, Nishijima Hospital, Numazu City, Sizuoka, Japan (H.O.); and Portland VA Medical Center, OR (J.S.C.).
authors.forename: Justin S
authors.initials: JS
authors.lastname: Cetas
authors.affiliation: From the Department of Anesthesiology and Perioperative Medicine, The Knight Cardiovascular Institute (D.A.S., C.M.D., J.W.N., M.R.G., N.J.A.), Department of Neurological Surgery (D.A.S., J.S.C.), Advanced Imaging Research Center (Y.A.B., A.K., M.P.), Oregon Health and Science University, Portland; Department of Neurosurgery, Nishijima Hospital, Numazu City, Sizuoka, Japan (H.O.); and Portland VA Medical Center, OR (J.S.C.).
authors.forename: Martin
authors.initials: M
authors.lastname: Pike
authors.affiliation: From the Department of Anesthesiology and Perioperative Medicine, The Knight Cardiovascular Institute (D.A.S., C.M.D., J.W.N., M.R.G., N.J.A.), Department of Neurological Surgery (D.A.S., J.S.C.), Advanced Imaging Research Center (Y.A.B., A.K., M.P.), Oregon Health and Science University, Portland; Department of Neurosurgery, Nishijima Hospital, Numazu City, Sizuoka, Japan (H.O.); and Portland VA Medical Center, OR (J.S.C.). alkayedn@ohsu.edu.
authors.forename: Nabil J
authors.initials: NJ
authors.lastname: Alkayed
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000201:enzymology* / Q000473:pathology; D004851:Epoxide Hydrolases / Q000172:deficiency*; D007249:Inflammation / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013345:Subarachnoid Hemorrhage / Q000201:enzymology* / Q000473:pathology; D014657:Vasculitis / Q000201:enzymology* / Q000473:pathology
chemical_list: D004851:Epoxide Hydrolases
keywords: communicating hydrocephalus; edema; subarachnoid hemorrhage; vascular cell adhesion molecule-1