Butt Mark T
Tox Path Specialists, LLC, Frederick, MD, USA.
Toxicol Pathol. 2020 Jan;48(1):10-18. doi: 10.1177/0192623319862540. Epub 2019 Jul 25.
Many preclinical investigations limit the evaluation of the peripheral nervous system (PNS) to paraffin-embedded sections/hematoxylin and eosin-stained sections of the sciatic nerve. This limitation ignores several key mechanisms of toxicity and anatomic differences that may interfere with an accurate assessment of test article effects on the neurons/neurites peripheral to the brain and spinal cord. Ganglion neurons may be exposed to higher concentrations of the test article as compared to neurons in the brain or spinal cord due to differences in capillary permeability. Many peripheral neuropathies are length-dependent, meaning distal nerves may show morphological changes before they are evident in the mid-sciatic nerve. Paraffin-embedded nerves are not optimal to assess myelin changes, notably those leading to demyelination. Differentiating between axonal or myelin degeneration may not be possible from the examination of paraffin-embedded sections. A sampling strategy more consistent with known mechanisms of toxicity, atraumatic harvest of tissues, optimized fixation, and the use of resin and paraffin-embedded sections will greatly enhance the pathologist's ability to observe and characterize effects in the PNS.
许多临床前研究将外周神经系统（PNS）的评估局限于坐骨神经石蜡包埋切片/苏木精-伊红染色切片。这种局限性忽略了几种关键的毒性机制以及可能干扰准确评估受试物对脑和脊髓外周神经元/神经突影响的解剖学差异。由于毛细血管通透性的差异，神经节神经元可能比脑或脊髓中的神经元接触到更高浓度的受试物。许多周围神经病变是长度依赖性的，这意味着远端神经可能在坐骨神经中部出现明显变化之前就表现出形态学改变。石蜡包埋的神经对于评估髓鞘变化并非最佳选择，尤其是那些导致脱髓鞘的变化。通过检查石蜡包埋切片可能无法区分轴突或髓鞘变性。一种更符合已知毒性机制的采样策略、无创伤性获取组织、优化固定以及使用树脂和石蜡包埋切片将极大地提高病理学家观察和描述PNS中效应的能力。
