PMID- 33129262 OWN - NLM STAT- MEDLINE DCOM- 20210902 LR - 20240331 IS - 1471-2202 (Electronic) IS - 1471-2202 (Linking) VI - 21 IP - 1 DP - 2020 Oct 31 TI - Neurologic effects of short-term treatment with a soluble epoxide hydrolase inhibitor after cardiac arrest in pediatric swine. PG - 43 LID - 10.1186/s12868-020-00596-y [doi] LID - 43 AB - BACKGROUND: Cardiac arrest (CA) is the most common cause of acute neurologic insult in children. Many survivors have significant neurocognitive deficits at 1 year of recovery. Epoxyeicosatrienoic acids (EETs) are multifunctional endogenous lipid signaling molecules that are involved in brain pathobiology and may be therapeutically relevant. However, EETs are rapidly metabolized to less active dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH), limiting their bioavailability. We hypothesized that sEH inhibition would improve outcomes after CA in an infant swine model. Male piglets (3-4 kg, 2 weeks old) underwent hypoxic-asphyxic CA. After resuscitation, they were randomized to intravenous treatment with an sEH inhibitor (TPPU, 1 mg/kg; n = 8) or vehicle (10% poly(ethylene glycol); n = 9) administered at 30 min and 24 h after return of spontaneous circulation. Two sham-operated groups received either TPPU (n = 9) or vehicle (n = 8). Neurons were counted in hematoxylin- and eosin-stained sections from putamen and motor cortex in 4-day survivors. RESULTS: Piglets in the CA + vehicle groups had fewer neurons than sham animals in both putamen and motor cortex. However, the number of neurons after CA did not differ between vehicle- and TPPU-treated groups in either anatomic area. Further, 20% of putamen neurons in the Sham + TPPU group had abnormal morphology, with cell body attrition and nuclear condensation. TPPU treatment also did not reduce neurologic deficits. CONCLUSION: Treatment with an sEH inhibitor at 30 min and 24 h after resuscitation from asphyxic CA does not protect neurons or improve acute neurologic outcomes in piglets. FAU - O'Brien, Caitlin E AU - O'Brien CE AUID- ORCID: 0000-0002-5609-1955 AD - Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 1800 Orleans Street, Bloomberg Children's Center Suite 6302, Baltimore, MD, 21287, USA. cobrie19@jhmi.edu. FAU - Santos, Polan T AU - Santos PT AD - Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 1800 Orleans Street, Bloomberg Children's Center Suite 6302, Baltimore, MD, 21287, USA. FAU - Kulikowicz, Ewa AU - Kulikowicz E AD - Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 1800 Orleans Street, Bloomberg Children's Center Suite 6302, Baltimore, MD, 21287, USA. FAU - Lee, Jennifer K AU - Lee JK AD - Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 1800 Orleans Street, Bloomberg Children's Center Suite 6302, Baltimore, MD, 21287, USA. AD - Pathobiology Graduate Training Program, Johns Hopkins University School of Medicine, 1800 Orleans Street, Bloomberg Children's Center Suite 6302, Baltimore, MD, 21287, USA. FAU - Koehler, Raymond C AU - Koehler RC AD - Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 1800 Orleans Street, Bloomberg Children's Center Suite 6302, Baltimore, MD, 21287, USA. FAU - Martin, Lee J AU - Martin LJ AD - Department of Pathology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD, 21287, USA. AD - Pathobiology Graduate Training Program, Johns Hopkins University School of Medicine, 1800 Orleans Street, Bloomberg Children's Center Suite 6302, Baltimore, MD, 21287, USA. LA - eng GR - P50 AG005146/AG/NIA NIH HHS/United States GR - R01 NS113921/NS/NINDS NIH HHS/United States GR - R01 NS109029/NS/NINDS NIH HHS/United States GR - R01 NS107417/NS/NINDS NIH HHS/United States GR - R01 NS060703/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20201031 PL - England TA - BMC Neurosci JT - BMC neuroscience JID - 100966986 RN - 0 (1-trifluoromethoxyphenyl-3-(1-propionylpiperidine-4-yl)urea) RN - 0 (Enzyme Inhibitors) RN - 0 (Phenylurea Compounds) RN - 0 (Piperidines) RN - EC 3.3.2.- (Epoxide Hydrolases) SB - IM MH - Animals MH - Asphyxia/pathology MH - Cell Death MH - Endoplasmic Reticulum Stress MH - Enzyme Inhibitors/*therapeutic use MH - Epoxide Hydrolases/*antagonists & inhibitors MH - Heart Arrest/*complications MH - Male MH - Motor Cortex/pathology MH - Nervous System Diseases/*drug therapy/*etiology MH - Neurons/pathology MH - Phenylurea Compounds/therapeutic use MH - Piperidines/therapeutic use MH - Putamen/pathology MH - Swine MH - Treatment Outcome PMC - PMC7603774 OTO - NOTNLM OT - Basal ganglia OT - Brain damage OT - Cardiac arrest OT - Cell death OT - Neuroprotection OT - Piglet OT - TPPU COIS- The authors declare that they have no competing interests. EDAT- 2020/11/02 06:00 MHDA- 2021/09/03 06:00 PMCR- 2020/10/31 CRDT- 2020/11/01 20:23 PHST- 2020/07/16 00:00 [received] PHST- 2020/10/09 00:00 [accepted] PHST- 2020/11/01 20:23 [entrez] PHST- 2020/11/02 06:00 [pubmed] PHST- 2021/09/03 06:00 [medline] PHST- 2020/10/31 00:00 [pmc-release] AID - 10.1186/s12868-020-00596-y [pii] AID - 596 [pii] AID - 10.1186/s12868-020-00596-y [doi] PST - epublish SO - BMC Neurosci. 2020 Oct 31;21(1):43. doi: 10.1186/s12868-020-00596-y.