Intranasal Administration of Interferon Beta Attenuates Neuronal Apoptosis via the JAK1/STAT3/BCL-2 Pathway in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy.
Intranasal Administration of Interferon Beta Attenuates Neuronal Apoptosis via the JAK1/STAT3/BCL-2 Pathway in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy.
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DOI：
10.1177/1759091416670492
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发表时间：
2016-10
期刊：
影响因子：
4.7
通讯作者：
Tang J
中科院分区：
文献类型：
--
作者：
Dixon BJ;Chen D;Zhang Y;Flores J;Malaguit J;Nowrangi D;Zhang JH;Tang J
新生儿缺氧缺血性脑病（HIE）是一种常导致有害神经功能缺损的损伤。目前，对于HIE尚无既定的治疗方法，开发在HIE后提供保护的治疗方法至关重要。本研究的目的是探讨干扰素β（IFNβ）在HIE后提供神经保护和减少细胞凋亡的能力。出生后第10天的大鼠幼崽接受单侧颈动脉结扎，随后暴露于缺氧环境（8% O₂）2.5小时。在HIE发生2小时后进行人重组IFNβ鼻腔给药，并使用梗死体积、体重、神经行为测试、组织学、免疫组织化学、脑含水量、血脑屏障通透性、酶联免疫吸附测定和蛋白质印迹等方法来评估各种参数。结果显示，HIE后IFNβ和1型干扰素受体的表达均降低。人重组IFNβ鼻腔给药能够在中枢神经系统中被检测到，并且能够在HIE后24小时减少脑梗死体积并改善神经行为测试。蛋白质印迹分析还显示，人重组IFNβ治疗刺激了Stat3和Bcl - 2的表达，导致HIE后裂解的caspase - 3表达降低。Fluoro - Jade C阳性染色也表明IFNβ治疗能够减少神经元凋亡。此外，当应用Stat3抑制剂时，IFNβ治疗的有益效果被逆转。而且，向全身给药人重组IFNβ（腹腔给药）无法产生与鼻腔IFNβ治疗相同的保护效果。
Neonatal hypoxic-ischemic encephalopathy (HIE) is an injury that often leads to detrimental neurological deficits. Currently, there are no established therapies for HIE and it is critical to develop treatments that provide protection after HIE. The objective of this study was to investigate the ability of interferon beta (IFNβ) to provide neuroprotection and reduce apoptosis after HIE. Postnatal Day 10 rat pups were subjected to unilateral carotid artery ligation followed by 2.5 hr of exposure to hypoxia (8% O2). Intranasal administration of human recombinant IFNβ occurred 2 hr after HIE and infarct volume, body weight, neurobehavioral tests, histology, immunohistochemistry, brain water content, blood–brain barrier permeability, enzyme-linked immunosorbent assay, and Western blot were all used to evaluate various parameters. The results showed that both IFNβ and the Type 1 interferon receptor expression decreases after HIE. Intranasal administration of human recombinant IFNβ was able to be detected in the central nervous system and was able to reduce brain infarction volumes and improve neurological behavior tests 24 hr after HIE. Western blot analysis also revealed that human recombinant IFNβ treatment stimulated Stat3 and Bcl-2 expression leading to a decrease in cleaved caspase-3 expression after HIE. Positive Fluoro-Jade C staining also demonstrated that IFNβ treatment was able to decrease neuronal apoptosis. Furthermore, the beneficial effects of IFNβ treatment were reversed when a Stat3 inhibitor was applied. Also an intraperitoneal administration of human recombinant IFNβ into the systemic compartment was unable to confer the same protective effects as intranasal IFNβ treatment.
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影响因子：
6.9
作者：
Chen, Hank;Burris, Michael;Fajilan, Adrain;Spagnoli, Fred;Zhang, John H.;Tang, Jiping
通讯作者：
Tang, Jiping
影响因子：
8.3
作者：
Chen W;Ma Q;Suzuki H;Hartman R;Tang J;Zhang JH
通讯作者：
Zhang JH
影响因子：
2.9
作者：
Askalan, Rand;Gabarin, Nadia;Yager, Jerome Y.
通讯作者：
Yager, Jerome Y.
影响因子：
6.9
作者：
Chen, Qianwei;Zhang, Jianbo;Chen, Zhi
通讯作者：
Chen, Zhi
影响因子：
6.9
作者：
Doycheva, Desislava;Shih, Gary;Chen, Hank;Applegate, Richard;Zhang, John H.;Tang, Jiping
通讯作者：
Tang, Jiping