PMID- 23540655 OWN - NLM STAT- MEDLINE DCOM- 20140115 LR - 20211021 IS - 1097-685X (Electronic) IS - 0022-5223 (Print) IS - 0022-5223 (Linking) VI - 146 IP - 6 DP - 2013 Dec TI - Rodent brain slice model for the study of white matter injury. PG - 1526-1533.e1 LID - S0022-5223(13)00269-9 [pii] LID - 10.1016/j.jtcvs.2013.02.071 [doi] AB - OBJECTIVE: Cerebral white matter (WM) injury is common after cardiac surgery in neonates and young infants who have brain immaturity and genetic abnormalities. To understand better the mechanisms associated with WM injury, we tested the adequacy of a novel ex vivo brain slice model, with a particular focus on how the maturational stage modulates the injury. METHODS: To replicate conditions of cardiopulmonary bypass, we transferred living brain slices to a closed chamber perfused by artificial cerebrospinal fluid under controlled temperature and oxygenation. Oxygen-glucose deprivation (OGD) simulated circulatory arrest. The effects of maturation were investigated in 7- and 21-day-old mice (P7, P21) that are equivalent in maturation stage to the human fetus and young adult. RESULTS: There were no morphologic changes in axons after 60 minutes of OGD at 15 degrees C in both P7 WM and P21 WM. Higher temperature and longer duration of OGD were associated with significantly greater WM axonal damage, suggesting that the model replicates the injury seen after hypothermic circulatory arrest. The axonal damage at P7 was significantly less than at P21, demonstrating that immature axons are more resistant than mature axons. Conversely, a significant increase in caspase3(+) oligodendrocytes in P7 mice was identified relative to P21, indicating that oligodendrocytes in immature WM are more vulnerable than oligodendrocytes in mature WM. CONCLUSIONS: Neuroprotective strategies for immature WM may need to focus on reducing oligodendrocyte injury. The brain slice model will be helpful in understanding the effects of cardiac surgery on the immature brain and the brain with genetic abnormalities. CI - Copyright (c) 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved. FAU - Murata, Akira AU - Murata A AD - Children's National Heart Institute, Children's National Medical Center, Washington, DC; Center for Neuroscience Research, Children's National Medical Center, Washington, DC. FAU - Agematsu, Kota AU - Agematsu K FAU - Korotcova, Ludmila AU - Korotcova L FAU - Gallo, Vittorio AU - Gallo V FAU - Jonas, Richard A AU - Jonas RA FAU - Ishibashi, Nobuyuki AU - Ishibashi N LA - eng GR - P01 NS062686/NS/NINDS NIH HHS/United States GR - P30 HD040677/HD/NICHD NIH HHS/United States GR - P30HD040677/HD/NICHD NIH HHS/United States GR - R01HL104173/HL/NHLBI NIH HHS/United States GR - P01 NS0626860/NS/NINDS NIH HHS/United States GR - R01NS045702/NS/NINDS NIH HHS/United States GR - R01 HL060922/HL/NHLBI NIH HHS/United States GR - R01 HL104173/HL/NHLBI NIH HHS/United States GR - R01 NS045702/NS/NINDS NIH HHS/United States GR - R01HL060922/HL/NHLBI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20130327 PL - United States TA - J Thorac Cardiovasc Surg JT - The Journal of thoracic and cardiovascular surgery JID - 0376343 RN - 0 (Bacterial Proteins) RN - 0 (Luminescent Proteins) RN - 0 (enhanced green fluorescent protein) RN - 0 (yellow fluorescent protein, Bacteria) RN - 147336-22-9 (Green Fluorescent Proteins) RN - EC 3.4.22.- (Casp3 protein, rat) RN - EC 3.4.22.- (Caspase 3) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Age Factors MH - Animals MH - Axons/metabolism/pathology MH - Bacterial Proteins/biosynthesis/genetics MH - Brain/growth & development/metabolism/*pathology MH - Cardiopulmonary Bypass/*adverse effects MH - Caspase 3/metabolism MH - Cell Hypoxia MH - Circulatory Arrest, Deep Hypothermia Induced/*adverse effects MH - Glucose/deficiency MH - Green Fluorescent Proteins/biosynthesis/genetics MH - In Vitro Techniques MH - Leukoencephalopathies/etiology/metabolism/*pathology/prevention & control MH - Luminescent Proteins/biosynthesis/genetics MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Oligodendroglia/metabolism/pathology MH - Perfusion MH - Temperature MH - Time Factors PMC - PMC3724768 MID - NIHMS451569 OTO - NOTNLM OT - 19 OT - 20 OT - 25 OT - 2',3'-cyclic nucleotide 3'phosphodiesterase OT - CHD OT - CNP OT - CPB OT - DHCA OT - OGD OT - PBS OT - WM OT - aCSF OT - artificial cerebrospinal fluid OT - cardiopulmonary bypass OT - congenital heart disease OT - deep hypothermic circulatory arrest OT - oxygen-glucose deprivation OT - phosphate-buffered saline OT - white matter COIS- Conflict of Interest: None EDAT- 2013/04/02 06:00 MHDA- 2014/01/16 06:00 PMCR- 2014/12/01 CRDT- 2013/04/02 06:00 PHST- 2012/12/25 00:00 [received] PHST- 2013/02/13 00:00 [revised] PHST- 2013/02/28 00:00 [accepted] PHST- 2013/04/02 06:00 [entrez] PHST- 2013/04/02 06:00 [pubmed] PHST- 2014/01/16 06:00 [medline] PHST- 2014/12/01 00:00 [pmc-release] AID - S0022-5223(13)00269-9 [pii] AID - 10.1016/j.jtcvs.2013.02.071 [doi] PST - ppublish SO - J Thorac Cardiovasc Surg. 2013 Dec;146(6):1526-1533.e1. doi: 10.1016/j.jtcvs.2013.02.071. Epub 2013 Mar 27.