中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (10): 1025-1030.doi: 10.4103/1673-5374.133161

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

神经生长因子鼻腔给药修复损伤的脊髓神经元

  

  • 收稿日期:2014-03-20 出版日期:2014-05-26 发布日期:2014-05-26

Intranasal nerve growth factor bypasses the blood-brain barrier and affects spinal cord neurons in spinal cord injury

Luigi Aloe 1, Patrizia Bianchi 1, Alberto De Bellis 2, Marzia Soligo 3, Maria Luisa Rocco 1   

  1. 1 Cellular Biology and Neurobiology Institute, National Research Council (CNR), Rome, Italy
    2 Maria Rosaria Maglione Foundation Onlus, Napoli, Italy
    3 Intitute of Translational Pharmacology, National Research Council (CNR), Rome, Italy
  • Received:2014-03-20 Online:2014-05-26 Published:2014-05-26
  • Contact: Luigi Aloe, Cellular Biology and Neurobiology Institute, National Research Council (CNR), Via del Fosso di Fiorano 64/65, 00143 Rome, Italy,luigi.aloe@inmm.cnr.it.
  • Supported by:

    This study was supported by Proj. PRIN prot. 2007AF3XH4_005, “Fondazione Cassa di Risparmio di Roma”, and “Ministero della Salute” Grant No. RF-FGB-2005-150198.

摘要:

神经生长因子可安全地经鼻腔进入大脑,从而成为治疗脑疾病的可能方法。我们假设神经生长因子鼻腔给药也可透过血脑屏障到达脊髓,逆转脊髓神经元损伤。实验结果发现,健康大鼠在单次给予神经生长因子24h后,脊髓中神经生长因子含量及其受体的表达均明显上升。神经生长因子给药3周后,不但提高了脊髓神经生长因子及其受体含量,而且改善了脊髓损伤大鼠运动功能。这些结果显示,神经生长因子鼻腔给药可透过血脑屏障,营养损伤的脊髓神经元。研究结果为神经生长因子鼻腔给药修复脊髓损伤提供了实验依据。

关键词: 神经再生, 脊髓损伤, 神经生长因子, 神经生长因子受体, 鼻腔给药, 血脑屏障, 运动功能, 瘦素, 神经保护, 大鼠

Abstract:

The purpose of this work was to investigate whether, by intranasal administration, the nerve growth factor bypasses the blood-brain barrier and turns over the spinal cord neurons and if such therapeutic approach could be of value in the treatment of spinal cord injury. Adult Sprague-Dawley rats with intact and injured spinal cord received daily intranasal nerve growth factor administration in both nostrils for 1 day or for 3 consecutive weeks. We found an increased content of nerve growth factor and enhanced expression of nerve growth factor receptor in the spinal cord 24 hours after a single intranasal administration of nerve growth factor in healthy rats, while daily treatment for 3 weeks in a model of spinal cord injury improved the deficits in locomotor behaviour and increased spinal content of both nerve growth factor and nerve growth factor receptors. These outcomes suggest that the intranasal nerve growth factor bypasses blood-brain barrier and affects spinal cord neurons in spinal cord injury. They also suggest exploiting the possible therapeutic role of intranasally delivered nerve growth factor for the neuroprotection of damaged spinal nerve cells.

Key words: nerve regeneration, spinal cord injury, nerve growth factor, intranasal delivery, blood-brain barrier, motor function, leptin, neuroprotection, rats, neural regeneration