Intranasal delivery of bFGF with nanoliposomes enhances in vivo neuroprotection and neural injury recovery in a rodent stroke model.
Intranasal delivery of bFGF with nanoliposomes enhances in vivo neuroprotection and neural injury recovery in a rodent stroke model.
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DOI：
10.1016/j.jconrel.2016.01.017
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发表时间：
2016-02
期刊：
影响因子：
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通讯作者：
Ying-zheng Zhao;Min Lin;Qian Lin;Wei Yang;Xi-chong Yu;Fu-Rong Tian;Kaili Mao;Jing-jing Yang;Cui-tao Lu;H. Wong
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文献类型：
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作者：
Ying-zheng Zhao;Min Lin;Qian Lin;Wei Yang;Xi-chong Yu;Fu-Rong Tian;Kaili Mao;Jing-jing Yang;Cui-tao Lu;H. Wong
碱性成纤维细胞生长因子（bFGF）可以保护中风患者免受脑缺血再灌注（I/R）损伤。在这项研究中，我们报告了在脑 I/R 大鼠模型中鼻内使用新型纳米脂质体向大脑输送 bFGF。与游离bFGF相比，纳米脂质体治疗能够显着改善脑组织中bFGF的积累（p<0.05），包括受影响最严重的缺血半暗带区域（例如海马、大脑皮层）。连续 3 天鼻内 bFGF-纳米脂质体治疗后，观察到神经功能缺损评分和自发运动活动改善所表明的功能恢复，并且中风梗塞体积几乎减半（p < 0.001），并在 21 天后持续存在。这些神经保护作用可以被 PI3-K/Akt 抑制剂 LY294002 阻断，表明 PI3-K/Akt 激活参与了治疗作用。总体而言，我们的结果支持鼻内使用纳米脂质体 bFGF 作为绕过血脑屏障治疗缺血性中风的有效、非侵入性方法。
Basic fibroblast growth factor (bFGF) may protect stroke patients from cerebral ischemia–reperfusion (I/R) injury. In this study, we report the intranasal use of novel nanoliposomes for the brain delivery of bFGF in a rat model of cerebral I/R. Compared with free bFGF, nanoliposomal therapy was able to significantly improve bFGF accumulation in brain tissues (p< 0.05) including the most affected ischemic penumbra regions (e.g.hippocampus, pallium). After intranasal bFGF-nanoliposomal treatment for 3 consecutive days, functional recovery as indicated by improved neurologic deficit score and spontaneous locomotor activity was observed, and the stroke infarct volume was nearly halved (p< 0.001) which persisted after 21 days. These neuroprotective effects could be blocked by the PI3-K/Akt inhibitor LY294002, indicating the involvement of PI3-K/Akt activation in the therapeutic action. Overall, our results support the intranasal use of nanoliposomal bFGF as an efficient, non-invasive means to bypass the blood–brain barrier for ischemic stroke treatment.