title: Extracellular amino acids and lipid peroxidation products in periventricular white matter during and after cerebral ischemia in preterm fetal sheep.
abstract: It is widely hypothesized that accumulation of excitatory amino acids, and oxygen free radicals during or after exposure to hypoxia-ischemia play a pivotal role in preterm periventricular white matter injury; however, there is limited evidence in the intact brain. In preterm fetal sheep (0.65 gestation; term 147 days) we found no significant increase in extracellular levels of excitatory amino acids measured by microdialysis in the periventricular white matter during cerebral ischemia induced by bilateral carotid occlusion. There was no significant change in 8-isoprostane or malondialdehyde levels in the early phase of recovery after occlusion. In contrast, there was a significant delayed increase in most amino acids and in malondialdehyde (but not 8-isoprostane) that was maximal approximately 2-3 days after occlusion. The increase in glutamate was significantly correlated with a secondary increase in cortical impedance, an index of cytotoxic edema, and with white matter damage 3 days post-insult. In conclusion, no significant accumulation of cytotoxins was found within immature white matter during cerebral ischemia. Although a minority of fetuses showed a delayed increase in some cytotoxins, this occurred many days after ischemia, in association with secondary cytotoxic edema, strongly suggesting that these changes are mainly a consequence of evolving cell death.
authors.affiliation: Liggins Institute, University of Auckland, Auckland, New Zealand. m.fraser@auckland.ac.nz
authors.forename: Mhoyra
authors.initials: M
authors.lastname: Fraser
authors.forename: Laura
authors.initials: L
authors.lastname: Bennet
authors.forename: Pierre L
authors.initials: PL
authors.lastname: Van Zijl
authors.forename: Tessa J
authors.initials: TJ
authors.lastname: Mocatta
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Williams
authors.forename: Peter D
authors.initials: PD
authors.lastname: Gluckman
authors.forename: Christine C
authors.initials: CC
authors.lastname: Winterbourn
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Gunn
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000196:embryology / Q000378:metabolism*; D002552:Cerebral Ventricles / Q000378:metabolism; D018846:Excitatory Amino Acids / Q000378:metabolism*; D045604:Extracellular Fluid / Q000378:metabolism*; D005260:Female; D005315:Fetal Diseases / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000502:physiology*; D017551:Microdialysis; D009413:Nerve Fibers, Myelinated / Q000378:metabolism*; D011247:Pregnancy; D012756:Sheep
chemical_list: D018846:Excitatory Amino Acids