Reinhart Florian, Massri Nabil El, Chabrol Claude, Cretallaz Celine, Johnstone Daniel M, Torres Napoleon, Darlot Fannie, Costecalde Thomas, Stone Jonathan, Mitrofanis John, Benabid Alim-Louis, Moro Cécile
CEA, Leti, and Clinatec Departments, University Grenoble Alpes, Minatec Campus, Grenoble, France; and
Departments of 2 Anatomy and.
J Neurosurg. 2016 Jun;124(6):1829-41. doi: 10.3171/2015.5.JNS15735. Epub 2015 Nov 27.
OBJECT The authors of this study used a newly developed intracranial optical fiber device to deliver near-infrared light (NIr) to the midbrain of 6-hydroxydopamine (6-OHDA)-lesioned rats, a model of Parkinson's disease. The authors explored whether NIr had any impact on apomorphine-induced turning behavior and whether it was neuroprotective. METHODS Two NIr powers (333 nW and 0.16 mW), modes of delivery (pulse and continuous), and total doses (634 mJ and 304 J) were tested, together with the feasibility of a midbrain implant site, one considered for later use in primates. Following a striatal 6-OHDA injection, the NIr optical fiber device was implanted surgically into the midline midbrain area of Wistar rats. Animals were tested for apomorphine-induced rotations, and then, 23 days later, their brains were aldehyde fixed for routine immunohistochemical analysis. RESULTS The results showed that there was no evidence of tissue toxicity by NIr in the midbrain. After 6-OHDA lesion, regardless of mode of delivery or total dose, NIr reduced apomorphine-induced rotations at the stronger, but not at the weaker, power. The authors found that neuroprotection, as assessed by tyrosine hydroxylase expression in midbrain dopaminergic cells, could account for some, but not all, of the observed behavioral improvements; the groups that were associated with fewer rotations did not all necessarily have a greater number of surviving cells. There may have been other "symptomatic" elements contributing to behavioral improvements in these rats. CONCLUSIONS In summary, when delivered at the appropriate power, delivery mode, and dosage, NIr treatment provided both improved behavior and neuroprotection in 6-OHDA-lesioned rats.
目的 本研究的作者使用一种新开发的颅内光纤装置,将近红外光(NIr)照射到6-羟基多巴胺(6-OHDA)损伤大鼠的中脑,该大鼠模型用于模拟帕金森病。作者探究了NIr是否对阿扑吗啡诱导的旋转行为有任何影响,以及它是否具有神经保护作用。方法 测试了两种NIr功率(333 nW和0.16 mW)、照射模式(脉冲和连续)和总剂量(634 mJ和304 J),以及中脑植入部位的可行性,该部位后来考虑用于灵长类动物。在纹状体注射6-OHDA后,将NIr光纤装置通过手术植入Wistar大鼠的中脑中线区域。对动物进行阿扑吗啡诱导的旋转测试,然后在23天后,将其大脑用醛固定以进行常规免疫组织化学分析。结果 结果表明,在中脑没有证据表明NIr具有组织毒性。在6-OHDA损伤后,无论照射模式或总剂量如何,NIr在较强功率下可减少阿扑吗啡诱导的旋转,但在较弱功率下则不然。作者发现,通过中脑多巴胺能细胞中酪氨酸羟化酶的表达评估的神经保护作用,可以解释部分但不是全部观察到的行为改善;与旋转次数较少相关的组并不一定都有更多存活的细胞。这些大鼠行为改善可能还有其他“对症”因素。结论 总之,当以适当的功率、照射模式和剂量进行照射时,NIr治疗可改善6-OHDA损伤大鼠的行为并具有神经保护作用。