title: Rodent brain slice model for the study of white matter injury.
abstract: 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°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.
authors.affiliation: Children's National Heart Institute, Children's National Medical Center, Washington, DC; Center for Neuroscience Research, Children's National Medical Center, Washington, DC.
authors.forename: Akira
authors.initials: A
authors.lastname: Murata
authors.forename: Kota
authors.initials: K
authors.lastname: Agematsu
authors.forename: Ludmila
authors.initials: L
authors.lastname: Korotcova
authors.forename: Vittorio
authors.initials: V
authors.lastname: Gallo
authors.forename: Richard A
authors.initials: RA
authors.lastname: Jonas
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ishibashi
mesh_terms: D000367:Age Factors; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D001921:Brain / Q000254:growth & development / Q000378:metabolism / Q000473:pathology*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia; D050792:Circulatory Arrest, Deep Hypothermia Induced / Q000009:adverse effects*; D005947:Glucose / Q000172:deficiency; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D066298:In Vitro Techniques; D056784:Leukoencephalopathies / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D010477:Perfusion; D013696:Temperature; D013997:Time Factors
chemical_list: D001426:Bacterial Proteins; D008164:Luminescent Proteins; C485184:enhanced green fluorescent protein; C054562:yellow fluorescent protein, Bacteria; D049452:Green Fluorescent Proteins; C505410:Casp3 protein, rat; D053148:Caspase 3; D005947:Glucose
keywords: 19; 20; 25; 2′,3′-cyclic nucleotide 3′phosphodiesterase; CHD; CNP; CPB; DHCA; OGD; PBS; WM; aCSF; artificial cerebrospinal fluid; cardiopulmonary bypass; congenital heart disease; deep hypothermic circulatory arrest; oxygen-glucose deprivation; phosphate-buffered saline; white matter
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