Using dynamic Magnetic Resonance Imaging (dMRI), blood-brain barrier (BBB) permeability (kPSp) and tissue interstitial leakage space (ve) were evaluated in zinc-deficient (ZnDF) male weanling Wistar rats following 3 days exposure to hyperoxia (85% O2). Temporal monitoring of T1-weighted MR image changes, following a bolus intravenous injection of gadolinium-DTPA, allowed estimation of BBB integrity. Three-day exposure of hyperoxia caused a marginal loss of BBB integrity, reflected in a slight increase in kPSp and ve, observed in both the animals fed adequate zinc (ZnAL) and pair-fed controls (ZnPF). However, zinc deficiency resulted in a significant increase in both kPSp and ve, indicating a severely disturbed BBB. In addition MR-visible free water was elevated in ZnDF brains following hyperoxia treatment indicating that a loss of BBB integrity may be associated with neuronal edema. The diminished BBB integrity may be free-radical mediated as the ratio of oxidized to reduced glutathione (GSSG:GSH) was significantly elevated.
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References
1.
CarneyJM, Starke-ReedPE, OliverCN, LandumRW, ChengMS, WuJF, FloydRA. Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss of temporal and spatial memory by chronic administration of the spin trapping compound N-tert-butyl-α-phenylnitrone. Proc Natl Acad Sci U S A88: 36333636, 1991.
2.
TyralaEE. Zinc and copper balances in preterm infants. Pediatrics77: 513517, 1986.
3.
KellyFJ. Free radical disorders of preterm infants. Br Med Bull49: 668678, 1993.
4.
GrazianiLJ, MitchellDG, KornhauserM, PidcockFS, MertonDA, StanleyC, McKeeL. Neurodevelopment of preterm infants: Neonatal neurosonographic and serum bilirubin studies. Pediatrics89: 229234, 1992.
5.
VolpeJJ. Brain injury in the premature infant: Is it preventable?Pediatr Res27: S28S33, 1990.
6.
BetzL. Oxygen free radicals and the brain microvasculature. In: PartridgeWM, Ed. The Blood-Brain Barrier. New York: Raven Press, p 303, 1993.
7.
BrayTM, BettgerWJ. The physiological role of zinc as an antioxidant. Free Radic Biol Med8: 281291, 1990.
8.
CunnaneSC. Zinc Clinical and Biochemical Significance. Boca Raton, FL: CRC Press, p 99, 1988.
9.
HammermuellerJD, BrayTM, BettgerWJ. Effect of zinc and copper deficiency in microsomal NADPH-dependent active oxygen generation in rat lung and liver. J Nutr117: 894901, 1987.
10.
OliverCN, Starke-ReedPE, StadtmanER, LiuGJ, CarneyJM, FloydRA. Oxidative damage to brain proteins, loss of glutamine synthetase activity, and production of free radicals during ischemia/reperfusion-induced injury to gerbil brain. Proc Natl Acad Sci U S A87: 51445147, 1990.
11.
LowryOH, RosebroughNJ, FarrAL, RandallRJ. Protein measurement with the Folin phenol reagent. J Biol Chem193: 265275, 1951.
12.
TietzeF. Enzymatic method for quantitative determination of nanogram amounts of total and oxidized glutathione: Applications to mammalian blood and other tissues. Anal Biochem27: 502522, 1969.
13.
ToftsPS, KermodeAG. Measurement of the blood-brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts. Magn Reson Med17: 357367, 1991.
14.
ToftsPS, BerkowitzB, SchnallMD. Quantitative analysis of dynamic Gd-DTPA enhancement in breast tumours using a permeability model. Magn Reson Med33: 564568, 1995.
15.
WeinmannHJ, GriesG, SpeckU. Gd-DTPA and low osmolar Gd chelates. In: RungeVM, Ed. Enhanced Magnetic Resonance Imaging. Toronto: CV Mosby Co., p 74, 1989.
16.
WeinmannJH, BraschRC, PressWR, WesbeyGE. Characteristics of gadolinium DTPA: A potential NMR contrast agent. Am J Roentgenol142: 619624, 1984.
CefaluWT, WangZQ, WerbelS, Bell FarrowA, CrouseJRIII, HinsonWH, TerryJG, AndersonR. Contribution of visceral fat mass to the insulin resistance of aging. Metab Clin Exp44: 954959, 1995.
20.
FullerMF, FowlerPA, McNeillG, FosterMA. Imaging techniques for the assessment of body composition. J Nutr124: 1546S1550S, 1994.
21.
JonesSJ, TuranoG, KrissA, ShawkatF, KendallB, ThompsonAJ. Visual evoked potentials in phenylketonuria: Association with brain MRI, dietary state, and IQ. J Neurol Neurosurg Psychiatry59: 260265, 1995.
22.
MollerHE, VermathenP, UllrichK, WeglageJ, KochHG, PetersPE. In vivo NMR spectroscopy in patients with phenylketonuria: Changes of cerebral phenylalanine levels under dietary treatment. Neuropediatrics26: 199202, 1995.
23.
FredstromS, RogosheskeJ, GuptaP, BumsLJ. Extrapyramidal symptoms in a BMT recipient with hyperintense basal ganglia and elevated manganese. Bone Marrow Transplant15: 989992, 1995.
24.
TaylorCG, TownerRA, JanzenEG, BrayTM. MRI detection of hyperoxia-induced lung edema in zinc-deficient rats. Free Radic Biol Med9: 229233, 1990.
25.
TaylorCG, BrayTM. Increased lung copper-zinc-superoxide dismutase activity and absence of magnetic resonance imaging-detectable lung damage in copper-deficient rats exposed to hyperoxia. J Nutr121: 467473, 1991.
26.
Weisglas-KuperusN, KootHM, BaertsW, FetterWP, SauerPJ. Behaviour problems of very low-birthweight children. Dev Med Child Neurol35: 406416, 1993.
27.
RossG, LipperEG, AuldPA. Educational status and school-related abilities of very low-birthweight, premature children. Pediatrics88: 11251134, 1991.
28.
NoseworthyMD, BrayTA. Effect of oxidative stress on brain damage detected by MRI and in vivo 31P-NMR. Free Radic Biol Med24: 942951, 1998.
29.
ShuklaA, ShuklaR, DikshitM, SrimalRC. Alterations in free radical scavenging mechanisms following blood-brain barrier disruption. Free Radic Biol Med15: 97100, 1993.
30.
TasdemirogluE, ChristenberryPD, ArdellJL, ChronisterRB, TaylorAE. Effects of antioxidants on the blood-brain barrier and postischemic hyperemia. Acta Neurochir131: 302309, 1994.
31.
PfisterHW, KoedelU, LorenzlS, TomaszA. Antioxidants attenuate microvascular changes in the early phase of experimental pneumococcal meningitis in rats. Stroke23: 17981804, 1992.
32.
BettgerWJ, O'dellBL. Physiological roles of zinc in the plasma membrane of mammalian cells. J Nutr Biochem4: 194207, 1993.
33.
RapoportSI. A model for brain edema. In: InabaY, KlatzoI, SpatzM, Eds. Brain Edema. Proceedings of the Sixth International Symposium. Berlin: Springer-Verlag, p 59, 1985.
34.
RothHP, KirchgessnerM. Calmodulin, zinc, and calcium concentration in tissues of zinc- and calcium-deficient rats. J Trace Elem Electrolytes Health Dis2: 7378, 1988.
35.
OteizaPI, HurleyLS, LonnerdalB, KeenCL. Effects of marginal zinc deficiency on microtubule polymerization in the developing rat brain. J Nutr118: 735738, 1988.
36.
DubinskyJM. Examination of the role of calcium in neuronal death. Ann N Y Acad Sci679: 3442, 1993.
37.
OkaA, BelliveauMJ, RosenbergPA, VolpeJJ. Vulnerability of oligodendroglia to glutamate: Pharmacology, mechanisms, and prevention. J Neurosci13: 14411453, 1993.
38.
GolubMS, TakeuchiPT, KeenCL, GershwinME, HendrickxAG, LonnerdalB. Modulation of behavioral performance of prepubertal monkeys by moderate dietary zinc deprivation. Am J Clin Nutr60: 238243, 1994.
39.
GuidolinD, PolatoP, VenturinG, ZanottiA, MocchegianiE, FabrisN, NunziMG. Correlation between zinc level in hippocampal mossy fibers and spatial memory in aged rats. Ann N Y Acad Sci673: 187193, 1992.
40.
DreostiIE. Neurobiology of zinc. In: MillsCF, Ed. Zinc and Human Biology. New York: Springer-Verlag, p 235, 1989.
41.
BushAI, PettingellWH, MulthaupG, ParadisMD, VonsattelJP, GusellaJF, BeyreutherK, MastersCL, TanziRE. Rapid induction of Aß amyloid formation by zinc. Science265: 14641467, 1994.
