Intranasal delivery of neurotrophic factors BDNF, CNTF, EPO, and NT-4 to the CNS.
Intranasal delivery of neurotrophic factors BDNF, CNTF, EPO, and NT-4 to the CNS.
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DOI：
10.3109/10611860903318134
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发表时间：
2010-04
影响因子：
4.5
通讯作者：
McLoon LK
中科院分区：
文献类型：
--
作者：
Alcalá-Barraza SR;Lee MS;Hanson LR;McDonald AA;Frey WH 2nd;McLoon LK
中枢神经系统(CNS)损伤通常会导致严重的神经元死亡和功能丧失。体外实验证明，脑源性神经营养因子(BDNF)、睫状神经营养因子(CNTF)和神经营养因子-4/5(NT-4/5)等神经营养因子可促进神经元存活。然而，由于这些大的蛋白质分子不能有效地穿过血脑屏障，向受损的中枢神经系统输送是困难的。鼻腔注射70μg[125I]放射性标记的脑源性神经营养因子、神经营养因子、神经营养因子-4或促红细胞生成素，可在25分钟内在脑实质内产生0.1nM~1.0nM神经营养素浓度。此外，这些神经营养因子不仅到达中枢神经系统，而且它们的存在浓度足以激活存续的PI3Kinase/Akt途径，即使在较低水平的神经营养因子被测量到的情况下也是如此。目前对中枢神经系统的创伤性、缺血性和压迫性损伤尚无有效的治疗方法。这种方法对于抢救受损的中枢神经系统组织，以维持患者的中枢神经系统功能具有潜在的临床意义。鼻腔给药方法具有以下特点：(1)给药简单，(2)非侵入性给药，(3)相对快速的中枢神经系统给药，(4)易于重复给药，(5)不需要药物修饰，(6)全身暴露最小。
Injury to the central nervous system (CNS) generally results in significant neuronal death and functional loss. In vitro experiments have demonstrated that neurotrophic factors such as brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and neurotrophin-4/5 (NT-4/5) can promote neuronal survival. However, delivery to the injured CNS is difficult as these large protein molecules do not efficiently cross the blood–brain barrier. Intranasal delivery of 70 μg [125I]-radiolabeled BDNF, CNTF, NT-4, or erythropoietin (EPO) resulted in 0.1–1.0 nM neurotrophin concentrations within 25 min in brain parenchyma. In addition, not only did these neurotrophic factors reach the CNS, they were present in sufficient concentrations to activate the prosurvival PI3Kinase/Akt pathway, even where lower levels of neurotrophic factors were measured. Currently traumatic, ischemic and compressive injuries to the CNS have no effective treatment. There is potential clinical relevancy of this method for rescuing injured CNS tissues in order to maintain CNS function in affected patients. The intranasal delivery method has great clinical potential due to (1) simplicity of administration, (2) noninvasive drug administration, (3) relatively rapid CNS delivery, (4) ability to repeat dosing easily, (5) no requirement for drug modification, and (6) minimal systemic exposure.
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影响因子：
3.7
作者：
Benedict, C;Hallschmid, M;Kern, W
通讯作者：
Kern, W
影响因子：
5.3
作者：
Canals, JM;Pineda, JR;Alberch, J
通讯作者：
Alberch, J
DOI：
10.1073/pnas.0500195102
发表时间：
2005-03-08
影响因子：
11.1
作者：
De Rosa, R;Garcia, AA;Cattaneo, A
通讯作者：
Cattaneo, A
DOI：
10.1073/pnas.90.6.2222
发表时间：
1993-03-15
影响因子：
11.1
作者：
CLATTERBUCK, RE;PRICE, DL;KOLIATSOS, VE
通讯作者：
KOLIATSOS, VE
影响因子：
1.7
作者：
DECKNER, ML;FRISEN, J;RISLING, M
通讯作者：
RISLING, M