Abstract
Introduction:
The aim of this study was to test whether dexamethasone (Dex) and betamethasone (Beta), two of the most commonly used corticosteroids, protect against lipopolysaccharide (LPS)-induced white matter damage and neurobehavioral dysfunction.
Methods:
LPS or sterile saline was injected into the brain white matter of rat pups at postnatal day 5 (P5), and Dex or Beta was given intraperitoneally to the rat pups 1 h before the LPS microinjection. Brain inflammatory response, brain damage, and myelination were examined at P6, P8, and P14. Neurobehavioral tests were performed from P3 through P22.
Results:
Our results demonstrate that Dex and Beta markedly diminish the LPS-induced brain inflammatory response, restore myelin basic protein (MBP) expression, and alleviate lateral ventricle dilation. Both corticosteroids demonstrate significant protection against most LPS-induced behavioral deficits, including those in rearing, vibrissa-elicited forelimb-placing, beam walking, learning, and elevated plus-maze test. Of note, only Beta improved the locomotion and stereotype dysfunction. In contrast to their beneficial effects, neither drug prevented LPS-induced delay in body weight gain from P6 through P21.
Discussion:
Our study suggests that if their adverse effects are minimized, corticosteroids may be the potential candidate drugs to prevent brain damage in premature infants.
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References
Leviton A, Dammann O . Coagulation, inflammation, and the risk of neonatal white matter damage. Pediatr Res 2004;55:541–5.
Dammann O, Leviton A . Inflammation, brain damage and visual dysfunction in preterm infants. Semin Fetal Neonatal Med 2006;11:363–8.
Khwaja O, Volpe JJ . Pathogenesis of cerebral white matter injury of prematurity. Arch Dis Child Fetal Neonatal Ed 2008;93:F153–61.
Pang Y, Cai Z, Rhodes PG . Disturbance of oligodendrocyte development, hypomyelination and white matter injury in the neonatal rat brain after intracerebral injection of lipopolysaccharide. Brain Res Dev Brain Res 2003;140:205–14.
Fan LW, Pang Y, Lin S, et al. Minocycline reduces lipopolysaccharide-induced neurological dysfunction and brain injury in the neonatal rat. J Neurosci Res 2005;82:71–82.
Cai Z, Lin S, Fan LW, Pang Y, Rhodes PG . Minocycline alleviates hypoxic-ischemic injury to developing oligodendrocytes in the neonatal rat brain. Neuroscience 2006;137:425–35.
Vexler ZS, Yenari MA . Does inflammation after stroke affect the developing brain differently than adult brain? Dev Neurosci 2009;31:378–93.
Cavalieri RL, Cohen WR . Antenatal steroid therapy: have we undervalued the risks? J Matern Fetal Neonatal Med 2006;19:265–9.
Lee BH, Stoll BJ, McDonald SA, Higgins RD; National Institute of Child Health and Human Development Neonatal Research Network. Adverse neonatal outcomes associated with antenatal dexamethasone versus antenatal betamethasone. Pediatrics 2006;117:1503–10.
Craig A, Ling Luo N, Beardsley DJ, et al. Quantitative analysis of perinatal rodent oligodendrocyte lineage progression and its correlation with human. Exp Neurol 2003;181:231–40.
Pang Y, Campbell L, Zheng B, Fan L, Cai Z, Rhodes P . Lipopolysaccharide-activated microglia induce death of oligodendrocyte progenitor cells and impede their development. Neuroscience 2010;166:464–75.
Cassatella MA, Gasperini S, Russo MP . Cytokine expression and release by neutrophils. Ann N Y Acad Sci 1997;832:233–42.
Grau AJ, Berger E, Sung KL, Schmid-Schönbein GW . Granulocyte adhesion, deformability, and superoxide formation in acute stroke. Stroke 1992;23:33–9.
Fan LW, Tien LT, Zheng B, et al. Dopaminergic neuronal injury in the adult rat brain following neonatal exposure to lipopolysaccharide and the silent neurotoxicity. Brain Behav Immun 2011;25:286–97.
Mann SA, Versmold B, Marx R, et al. Corticosteroids reverse cytokine-induced block of survival and differentiation of oligodendrocyte progenitor cells from rats. J Neuroinflammation 2008;5:39.
Melcangi RC, Cavarretta I, Magnaghi V, Ciusani E, Salmaggi A . Corticosteroids protect oligodendrocytes from cytokine-induced cell death. Neuroreport 2000;11:3969–72.
Ikeda T, Yang L, Ikenoue T, Mallard C, Hagberg H . Endotoxin-induced hypoxic-ischemic tolerance is mediated by up-regulation of corticosterone in neonatal rat. Pediatr Res 2006;59:56–60.
Lee BH, Stoll BJ, McDonald SA, Higgins RD; National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental outcomes of extremely low birth weight infants exposed prenatally to dexamethasone versus betamethasone. Pediatrics 2008;121:289–96.
Yeh TF, Lin YJ, Lin HC, et al. Outcomes at school age after postnatal dexamethasone therapy for lung disease of prematurity. N Engl J Med 2004;350:1304–13.
Abbasi S, Hirsch D, Davis J et al. Effect of single versus multiple courses of antenatal corticosteroids on maternal and neonatal outcome. Am J Obstet Gynecol 2000;182:1243–9.
Watson RE, Desesso JM, Hurtt ME, Cappon GD . Postnatal growth and morphological development of the brain: a species comparison. Birth Defects Res B Dev Reprod Toxicol 2006;77:471–84.
Altman J, Sudarshan K, Das GD, McCormick N, Barnes D . The influence of nutrition on neural and behavioral development. 3. Development of some motor, particularly locomotor patterns during infancy. Dev Psychobiol 1971;4:97–114.
Hermans RH, Hunter DE, McGivern RF, Cain CD, Longo LD . Behavioral sequelae in young rats of acute intermittent antenatal hypoxia. Neurotoxicol Teratol 1992;14:119–29.
Antoniou K, Papathanasiou G, Panagis G, Nomikos GG, Hyphantis T, Papadopoulou-Daifoti Z . Individual responses to novelty predict qualitative differences in d-amphetamine-induced open field but not reward-related behaviors in rats. Neuroscience 2004;123:613–23.
Woodlee MT, Asseo-García AM, Zhao X, Liu SJ, Jones TA, Schallert T . Testing forelimb placing “across the midline” reveals distinct, lesion-dependent patterns of recovery in rats. Exp Neurol 2005;191:310–7.
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Pang, Y., Fan, LW., Zheng, B. et al. Dexamethasone and betamethasone protect against lipopolysaccharide-induced brain damage in neonatal rats. Pediatr Res 71, 552–558 (2012). https://doi.org/10.1038/pr.2012.9
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DOI: https://doi.org/10.1038/pr.2012.9
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