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首页> 外文期刊>IBRO Reports >Remote tissue conditioning is neuroprotective against MPTP insult in mice
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Remote tissue conditioning is neuroprotective against MPTP insult in mice

机译：远程组织调节对小鼠的MPTP损伤具有神经保护作用

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Current treatments for Parkinson’s disease (PD) are primarily symptomatic, leaving a need for treatments that mitigate disease progression. One emerging neuroprotective strategy is remote tissue conditioning, in which mild stress in a peripheral tissue (e.g. a limb) induces protection of life-critical organs such as the brain. We evaluated the potential of two remote tissue conditioning interventions – mild ischemia and photobiomodulation – in protecting the brain against the parkinsonian neurotoxin MPTP. Further, we sought to determine whether combining these two interventions provided any added benefit.Male C57BL/6 mice (n=10/group) were pre-conditioned with either ischemia of the leg (4×5min cycles of ischemia/reperfusion), or irradiation of the dorsum with 670nm light (50mW/cm2, 3min), or both interventions, immediately prior to receiving two MPTP injections 24hours apart (50mg/kg total). Mice were sacrificed 6days later and brains processed for tyrosine hydroxylase immunohistochemistry.Stereological counts of functional dopaminergic neurons in the substantia nigra pars compacta revealed that both remote ischemia and remote photobiomodulation rescued around half of the neurons that were compromised by MPTP (p<0.001). Combining the two interventions provided no added benefit, rescuing only 40% of vulnerable neurons (p<0.01).The present results suggest that remote tissue conditioning, whether ischemia of a limb or photobiomodulation of the torso, induces protection of brain centers critical in PD. The lack of additional benefit when combining these two interventions suggests they may share common mechanistic pathways. Further research is needed to identify these pathways and determine the conditioning doses that yield optimal neuroprotection.
机译：目前针对帕金森氏病（PD）的治疗主要是对症治疗，因此需要缓解疾病进展的治疗方法。一种新兴的神经保护策略是远程组织调节，其中，外周组织（例如肢体）的轻度压力诱导了对生命至关重要的器官（如大脑）的保护。我们评估了两种远程组织调节干预措施（轻度缺血和光生物调节）在保护大脑免受帕金森氏神经毒素MPTP方面的潜力。此外，我们试图确定这两种干预措施的结合是否提供了额外的益处。雄性C57BL / 6小鼠（n = 10 /组）的腿部缺血（4×5min缺血/再灌注周期）或在间隔24小时接受两次MPTP注射之前（共50mg / kg），立即用670nm的光（50mW / cm2，3分钟）照射背部，或同时进行两种干预。 6天后处死小鼠，对大脑进行酪氨酸羟化酶免疫组织化学处理。黑质致密部中功能性多巴胺能神经元的立体计数显示，远端缺血和远端光生物调节都能挽救约一半受MPTP损害的神经元（p <0.001）。两种干预措施的结合并没有带来额外的益处，仅挽救了40％的脆弱神经元（p <0.01）。目前的结果表明，无论是肢体局部缺血还是躯体的光生物调节，远程组织调节都能诱导对PD至关重要的脑中枢的保护。 。将这两种干预措施结合使用时，缺乏额外的益处表明它们可能具有共同的机制途径。需要进一步的研究来鉴定这些途径并确定产生最佳神经保护作用的调节剂量。

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