Fine J M, Forsberg A C, Renner D B, Faltesek K A, Mohan K G, Wong J C, Arneson L C, Crow J M, Frey W H, Hanson L R
HealthPartners Institute for Education and Research, St Paul, MN, USA.
HealthPartners Institute for Education and Research, St Paul, MN, USA.
Brain Res. 2014 Jul 29;1574:96-104. doi: 10.1016/j.brainres.2014.05.048. Epub 2014 Jun 10.
Deferoxamine (DFO) has shown therapeutic promise for the treatment of Parkinson׳s disease (PD) as it has reduced both behavioral and biochemical deficits when injected into the brain of rodent models of PD. Intranasally administered DFO targets the brain directly but non-invasively and has been effective in animal models of stroke and Alzheimer׳s disease. In this study we sought to determine whether intranasal (IN) DFO could be neuroprotective for PD in a rat model. PD was induced with a unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle, while sham surgery rats received saline injections. Rats were pre-treated three times with either IN DFO or saline (starting 4 days before 6-OHDA), and post-treated twice/wk for one month before behavioral tests. In the apomorphine-induced rotational test, IN DFO significantly decreased the number of contralateral turns after injection of apomorphine HCl (p<0.05). Also, IN DFO significantly decreased limb asymmetry in the rearing tube as measured with contralateral limb touches (p<0.05). The IN DFO treatment yielded a trend towards decreased contralateral foot-slips on the tapered balance beam, though the difference was not significant. Finally, IN DFO-treated rats had increased preservation of tyrosine hydroxylase immunoreactive neurons in the substantia nigra (p<0.05). These results confirm that DFO is beneficial in a 6-OHDA model and demonstrate improvement in motor deficits and dopaminergic neuronal survival with non-invasive intranasal delivery, making this an attractive potential treatment for PD.
去铁胺（DFO）已显示出治疗帕金森病（PD）的前景，因为将其注入PD啮齿动物模型的大脑后，可减少行为和生化缺陷。经鼻给药的DFO可直接且无创地作用于大脑，并且在中风和阿尔茨海默病动物模型中已显示出效果。在本研究中，我们试图确定经鼻（IN）给予DFO对大鼠PD模型是否具有神经保护作用。通过向内侧前脑束单侧注射6-羟基多巴胺（6-OHDA）诱导PD，而假手术大鼠接受盐水注射。大鼠在注射6-OHDA前4天开始，用IN DFO或盐水预处理3次，并在行为测试前每周后处理2次，持续1个月。在阿扑吗啡诱导的旋转试验中，IN DFO显著减少了注射盐酸阿扑吗啡后的对侧旋转次数（p<0.05）。此外，通过对侧肢体触碰测量，IN DFO显著降低了饲养管中的肢体不对称性（p<0.05）。在锥形平衡木上，IN DFO治疗使对侧足滑有减少的趋势，尽管差异不显著。最后，经IN DFO治疗的大鼠黑质中酪氨酸羟化酶免疫反应性神经元的保存增加（p<0.05）。这些结果证实DFO在6-OHDA模型中有益，并表明无创经鼻给药可改善运动缺陷和多巴胺能神经元存活，使其成为一种有吸引力的PD潜在治疗方法。
