17beta-estradiol protects against hypoxic/ischemic white matter damage in the neonatal rat brain.
17beta-estradiol protects against hypoxic/ischemic white matter damage in the neonatal rat brain.
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DOI：
10.1002/jnr.22023
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发表时间：
2009-07
影响因子：
4.2
通讯作者：
Rosenberg, Paul A.
中科院分区：
文献类型：
--
作者：
Gerstner, Bettina;Lee, Joan;DeSilva, Tara M.;Jensen, Frances E.;Volpe, Joseph J.;Rosenberg, Paul A.
发育中的少突胶质细胞（pre-OL）极易受到缺氧缺血性损伤以及相关的兴奋性毒性和氧化应激的影响。17β-雌二醇在中枢神经系统的发育和功能中起重要作用，并具有神经保护作用。出生后循环雌激素的突然下降可能会增加发育中的OL对损伤的易感性。雌激素受体（ER）- α和ER-β均在OLs中表达。我们研究了17β-雌二醇对体外大鼠前OLs的氧-糖剥夺和氧化应激诱导的细胞死亡以及对体内缺氧缺血性脑损伤的影响。在存在或不存在17β-雌二醇的情况下，对培养物中的前OL进行氧-葡萄糖剥夺（OGD）或谷胱甘肽耗竭。LDH释放，Alcohol blue测定和相差显微镜用于评估细胞活力。在6日龄大鼠（P6）中通过单侧颈动脉结扎和缺氧（6%O2持续1小时）产生缺氧缺血性损伤。在手术前12小时，大鼠幼仔接受一次300或600 µg/kg 17β-雌二醇或溶剂腹腔注射。在P10通过髓鞘碱性蛋白（MBP）免疫细胞化学评估损伤。17β-雌二醇对OGD诱导的原代OL细胞死亡（EC 50 = 1.3 ± 0.46 × 10−9 M）和氧化应激具有显著的保护作用。此外，17β-雌二醇减弱了颈动脉结扎同侧P10幼仔中MBP标记的丢失。这些结果表明，雌激素在减轻缺氧缺血性和氧化损伤发展中的OL和在预防脑室周围白质软化症的潜在作用。
Developing oligodendrocytes (pre-OLs) are highly vulnerable to hypoxic-ischemic injury and associated excitotoxicity and oxidative stress. 17β-Estradiol plays an important role in the development and function of the CNS and is neuroprotective. The sudden drop in circulating estrogen after birth may enhance the susceptibility of developing OLs to injury. Estrogen receptor (ER)– α and ER-β are both expressed in OLs. We examined the effect of 17β-estradiol on oxygen-glucose deprivation and oxidative stress–induced cell death in rat pre-OLs in vitro and on hypoxic-ischemic brain injury in vivo. Pre-OLs in culture were subjected to oxygen-glucose deprivation (OGD) or glutathione depletion in the presence or absence of 17β-estradiol. LDH release, the Alamar blue assay, and phase-contrast microscopy were used to assess cell viability. Hypoxic-ischemic injury was generated in 6-day-old rats (P6) by unilateral carotid ligation and hypoxia (6% O2 for 1 hr). Rat pups received one intraperitoneal injection of 300 or 600 µg/kg 17β-estradiol or vehicle 12 hr prior to the surgical procedure. Injury was assessed by myelin basic protein (MBP) immunocytochemistry at P10. 17β-Estradiol produced significant protection against OGD-induced cell death in primary OLs (EC50 = 1.3 ± 0.46 × 10−9 M) and against oxidative stress. Moreover, 17β-estradiol attenuated the loss of MBP labeling in P10 pups ipsilateral to the carotid ligation. These results suggest a potential role for estrogens in attenuation of hypoxic-is-chemic and oxidative injury to developing OLs and in the prevention of periventricular leukomalacia.
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影响因子：
2.9
作者：
Choi, YC;Lee, JH;Lee, KS
通讯作者：
Lee, KS
影响因子：
3.7
作者：
ARAI, Y;MATSUMOTO, A
通讯作者：
MATSUMOTO, A
影响因子：
3.4
作者：
Baud, O;Haynes, RF;Rosenberg, PA
通讯作者：
Rosenberg, PA
影响因子：
2.5
作者：
DOBBING, J;SANDS, J
通讯作者：
SANDS, J
DOI：
10.1016/j.devbrainres.2004.03.006
发表时间：
2004-06-21
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Hilton, GD;Ndubuizu, AN;McCarthy, MM
通讯作者：
McCarthy, MM