Fabricius Katrine, Barkholt Pernille, Jelsing Jacob, Hansen Henrik H
Gubra, Hoersholm, Denmark.
Front Neuroanat. 2017 Dec 8;11:109. doi: 10.3389/fnana.2017.00109. eCollection 2017.
Stereological analysis is the optimal tool for quantitative assessment of brain morphological and cellular changes induced by neurotoxic lesions or treatment interventions. Stereological methods based on random sampling techniques yield unbiased estimates of particle counts within a defined volume, thereby providing a true quantitative estimate of the target cell population. Neurodegenerative diseases involve loss of specific neuron types, such as the midbrain tyrosine hydroxylase-positive dopamine neurons in Parkinson's disease and in animal models of nigrostriatal degeneration. Therefore, we applied an established automated physical disector principle in a fractionator design for efficient stereological quantitative analysis of tyrosine hydroxylase (TH)-positive dopamine neurons in the substantia nigra pars compacta of hemiparkinsonian rats with unilateral 6-hydroxydopamine (6-OHDA) lesions. We obtained reliable estimates of dopamine neuron numbers, and established the relationship between behavioral asymmetry and dopamine neuron loss on the lesioned side. In conclusion, the automated physical disector principle provided a useful and efficient tool for unbiased estimation of TH-positive neurons in rat midbrain, and should prove valuable for investigating neuroprotective strategies in 6-OHDA model of parkinsonism, while generalizing to other immunohistochemically-defined cell populations.
体视学分析是定量评估由神经毒性损伤或治疗干预引起的脑形态和细胞变化的最佳工具。基于随机抽样技术的体视学方法能够对限定体积内的颗粒数量进行无偏估计，从而对目标细胞群体进行真正的定量估计。神经退行性疾病涉及特定神经元类型的丧失，例如帕金森病以及黑质纹状体变性动物模型中的中脑酪氨酸羟化酶阳性多巴胺神经元。因此，我们将一种既定的自动物理分割器原理应用于分样器设计中，以对单侧6-羟基多巴胺（6-OHDA）损伤的偏侧帕金森病大鼠黑质致密部中酪氨酸羟化酶（TH）阳性多巴胺神经元进行高效的体视学定量分析。我们获得了多巴胺神经元数量的可靠估计值，并建立了行为不对称与损伤侧多巴胺神经元丢失之间的关系。总之，自动物理分割器原理为无偏估计大鼠中脑TH阳性神经元提供了一种有用且高效的工具，对于研究帕金森病6-OHDA模型中的神经保护策略应具有重要价值，同时也可推广应用于其他免疫组织化学定义的细胞群体。
