DEXAMETHASONE INDUCES NEURODEGENERATION BUT ALSO UP-REGULATES VASCULAR ENDOTHELIAL GROWTH FACTOR A IN NEONATAL RAT BRAINS
DEXAMETHASONE INDUCES NEURODEGENERATION BUT ALSO UP-REGULATES VASCULAR ENDOTHELIAL GROWTH FACTOR A IN NEONATAL RAT BRAINS
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DOI：
10.1016/j.neuroscience.2008.10.024
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发表时间：
2009-01-23
期刊：
影响因子：
3.3
通讯作者：
Bhatt, A. J.
中科院分区：
文献类型：
--
作者：
Feng, Y.;Rhodes, P. G.;Bhatt, A. J.
在早产儿中使用地塞米松（Dex）预防和/或治疗支气管肺发育不良可能会对早期神经发育产生不利影响，并可能导致脑容量损失。血管内皮生长因子A（VEGF），特别是VEGF（164）亚型具有神经营养、神经保护和神经发生促进作用。以前的研究表明，地塞米松通常下调VEGF。在本研究中，我们研究了地塞米松对新生大鼠脑生长和VEGF的影响。将每窝幼仔分为溶剂组（n=84）或Dex给药组（n=98）。Dex组中的大鼠幼崽接受三种不同的i. p. Dex方案之一，包括在出生后第3-6天逐渐减少剂量（分别为0.5、0.25、0.125和0.06 mg/kg），或在出生后第4-6天重复给药0.5或1 mg/kg/天，或单次给药0.031、0.06、0.125、出生后第6天0.25或0.5 mg/kg。分别采用酶联免疫吸附试验和实时逆转录聚合酶链反应测定大鼠幼鼠脑中三种主要VEGF剪接变体（VEGF（120）、VEGF（164）和VEGF（188））的总VEGF蛋白和mRNA表达。Dex治疗显著降低了体重和脑重量的增加。Dex的逐渐减量和重复剂量显著增加caspase-3活性、VEGF蛋白以及VEGF（164）和VEGF（188）剪接变体的mRNA表达，但单次剂量没有。我们的结论是，地塞米松是神经退行性的发育中的大脑，但也增加VEGF，这可能发挥神经营养和神经保护作用。(c)2009年IBRO。由爱思唯尔有限公司出版。保留所有权利。
The use of dexamethasone (Dex) in premature infants to prevent and/or treat bronchopulmonary dysplasia can adversely affect early neurodevelopment and probably result in loss of cerebral volume. Vascular endothelial growth factor A (VEGF), specifically VEGF(164) isoform has neurotrophic, neuroprotective and neurogenesis enhancing effects. Previous studies have demonstrated that Dex usually down-regulates VEGF. In the present study we investigated the effect of Dex on brain growth and VEGF in the neonatal rat brain. The pups in each litter were divided into the vehicle (n=84) or Dex-treated (n=98) groups. Rat pups in the Dex group received one of three different regimens of i.p. Dex which included tapering doses on postnatal days 3-6 (0.5, 0.25, 0.125 and 0.06 mg/kg, respectively), or repeated doses of 0.5 or 1 mg/kg/day on postnatal days 4-6 or single dose of 0.031, 0.06, 0.125, 0.25 or 0.5 mg/kg on postnatal day 6. The total VEGF protein and mRNA expression of the three main VEGF splice variants (VEGF(120), VEGF(164), and VEGF(188)) were measured in the rat pup brain using enzyme-linked immunosorbent assay and real-time reverse transcription polymerase chain reaction, respectively. Treatment with Dex significantly decreased the gain of body and brain weight. The tapering and repeated doses of Dex significantly increased caspase-3 activity, VEGF protein and the expression of mRNA of VEGF(164) and VEGF(188) splice variants but the single dose did not. We conclude that Dex is neurodegenerative in the developing brain but also increases VEGF which may play a neurotrophic and neuroprotective role. (c) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.