Intranasal administration of IGF-1 attenuates hypoxic-ischemic brain injury in neonatal rats.
Intranasal administration of IGF-1 attenuates hypoxic-ischemic brain injury in neonatal rats.
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DOI：
10.1016/j.expneurol.2009.03.021
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发表时间：
2009-06
影响因子：
5.3
通讯作者：
Cai, Zhengwei
中科院分区：
文献类型：
--
作者：
Lin, Shuying;Fan, Lir-Wan;Rhodes, Philip G.;Cai, Zhengwei
关键词：
为了确定鼻内给药（iN）重组人胰岛素样生长因子-1（rhIGF-1）是否对脑缺氧缺血（HI）后的新生大鼠脑提供神经保护，两个剂量的rhIGF-1在有或没有预先HI损伤的情况下，将50 μg（以1小时间隔）输注到出生后第7天（P7）大鼠幼仔的右鼻孔中（右颈总动脉结扎，随后暴露于8%氧气2小时）。我们的结果表明，rhIGF-1通过iN给药后30分钟成功地将其递送到脑中。在以下研究中，在HI后0、1或2 h以上述剂量向P7大鼠幼仔给予rhIGF-1。对照组中的幼仔接受脑HI和溶剂处理。接受假手术和溶剂处理的幼仔作为假手术组。HI后2、15 d观察脑组织病理学变化。我们的研究结果表明，rhIGF-1治疗脑HI后1小时有效地减少脑损伤相比，在车辆处理的大鼠。此外，rhIGF-1治疗改善了HI幼年大鼠的神经行为表现（在P5-P21测试）。我们的结果进一步表明，rhIGF-1抑制凋亡细胞死亡，可能通过激活Akt信号转导通路。rhIGF-1也促进脑HI后神经元和少突胶质祖细胞的增殖。这些数据表明IGF-1的iN施用具有用于临床治疗的潜力。
To determine whether intranasal administration (iN) of recombinant human insulin-like growth factor-1 (rhIGF-1) provides neuroprotection to the neonatal rat brain following cerebral hypoxia-ischemia (HI), two doses of rhIGF-1 (50 μg at a 1 h interval) were infused into the right naris of postnatal day 7 (P7) rat pups with or without a prior HI insult (right common carotid artery ligation, followed by an exposure to 8% oxygen for 2 h). Our result showed that rhIGF-1 administered via iN was successfully delivered into the brain 30 min after the second dose. In the following studies rhIGF-1 was administered to P7 rat pups at 0, 1 or 2 h after HI at the dose described above. Pups in the control group received cerebral HI and vehicle treatment. Pups that underwent sham operation and vehicle treatment served as the sham group. Brain pathological changes were evaluated 2 and 15 d after HI. Our results showed that rhIGF-1 treatment up to 1 hr after cerebral HI effectively reduced brain injury as compared to that in the vehicle-treated rats. Moreover, rhIGF-1 treatment improved neurobehavioral performance (tested on P5-P21) in juvenile rats subjected to HI. Our results further showed that rhIGF-1 inhibited apoptotic cell death, possibly through activating the Akt signal transduction pathway. rhIGF-1 enhanced proliferation of neuronal and oligodendroglial progenitors after cerebral HI as well. These data suggest that iN administration of IGF-1 has the potential to be used for clinical treatment.
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影响因子：
4.7
作者：
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