Postnatal glucocorticoid-induced hypomyelination, gliosis, and neurologic deficits are dose-dependent, preparation-specific, and reversible.
Postnatal glucocorticoid-induced hypomyelination, gliosis, and neurologic deficits are dose-dependent, preparation-specific, and reversible.
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产后糖皮质激素诱导的低切髓和神经系统缺陷是剂量依赖性的，具有准备性的且可逆的。
DOI：
10.1016/j.expneurol.2014.09.013
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发表时间：
2015-01
影响因子：
5.3
通讯作者：
Ballabh, Praveen
中科院分区：
文献类型：
--
作者：
Zia, Muhammad T. K.;Vinukonda, Govindaiah;Vose, Linnea R.;Bhimavarapu, Bala B. R.;Iacobas, Sanda;Pandey, Nishi K.;Beall, Ann Marie;Dohare, Preeti;LaGamma, Edmund F.;Iacobas, Dumitru A.;Ballabh, Praveen
Postnatal glucocorticoids (GCs) are widely used in the prevention of chronic lung disease in premature infants. Their pharmacologic use is associated with neurodevelopmental delay and cerebral palsy. However, the effect of GC dose and preparation (dexamethasone versus betamethasone) on short and long-term neurological outcomes remains undetermined, and the mechanisms of GC-induced brain injury are unclear. We hypothesized that postnatal GC would induce hypomyelination and motor impairment in a preparation- and dose-specific manner, and that GC receptor (GR) inhibition might restore myelination and neurological function in GC-treated animals. Additionally, GC-induced hypomyelination and neurological deficit might be transient. To test our hypotheses, we treated prematurely delivered rabbit pups with high (0.5 mg/kg/day) or low (0.2 mg/kg/day) doses of dexamethasone or betamethasone. Myelin basic protein (MBP), oligodendrocyte proliferation and maturation, astrocytes, transcriptomic profile, and neurobehavioral functions were evaluated. We found that high-dose GC treatment, but not low-dose, reduced MBP expression and impaired motor function at postnatal day 14. High-dose dexamethasone induced astrogliosis, betamethasone did not. Mifepristone, a GR antagonist, reversed dexamethasone-induced myelination, but not astrogliosis. Both GCs inhibited oligodendrocyte proliferation and maturation. Moreover, high-dose dexamethasone altered genes associated with myelination, cell-cycle, GR, and Mitogen-activated protein kinase. Importantly, GC-induced hypomyelination, gliosis, and motor-deficit, observed at day 14, completely recovered by day 21. Hence, high-dose, but not low-dose, postnatal GC causes reversible reductions in myelination and motor functions. GC treatment induces hypomyelination by GR-dependent genomic mechanisms, but astrogliosis by non-genomic mechanisms. GC-induced motor impairment and neurodevelopmental delay might be transient and recover spontaneously in premature infants.
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影响因子：
8
作者：
Gross, SJ;Anbar, RD;Mettelman, BB
通讯作者：
Mettelman, BB
影响因子：
158.5
作者：
Baud, O;Foix-L'Helias, L;Lacaze-Masmonteil, T
通讯作者：
Lacaze-Masmonteil, T
影响因子：
2.9
作者：
Duksal, Fatma;Kilic, Ilknur;Akdogan, Ilgaz
通讯作者：
Akdogan, Ilgaz
影响因子：
8
作者：
Durand, M;Mendoza, ME;McEvoy, C
通讯作者：
McEvoy, C
DOI：
10.1016/s0736-5748(01)00026-0
发表时间：
2001-07-01
影响因子：
1.8
作者：
Huang, WL;Harper, CG;Dunlop, SA
通讯作者：
Dunlop, SA