影响药物毒性神经病理学评价质量的主要因素

神经毒性是许多药物或化合物常见的毒副作用。在新药研发早期要进行神经毒性筛选。对于可能通过血脑屏障影响神经系统的小分子药物或疫苗类的生物制品在临床前安全性评价中要进行非人灵长类动物的神经毒性评价。毒性病理学或神经病理学评价是临床前药物神经毒性评价的金标准。针对影响药物毒性神经病理学评价质量的几个主要因素,包括神经病理学评价的一般策略、最佳的评价时机、特殊的神经组织屏障系统、神经组织病理制片中的取材方法以及人工假象对神经病理学诊断的干扰,进行详细的解析,以期为我国神经毒性评价指导原则的制定和药物非临床神经毒性研究提供参考。

Major factors influencing quality of neuropathology evaluation of drug toxicology

Neurotoxicity is one common adverse effect caused by many drugs or compounds. In the early phase of new drug development, it is necessary to screen for neurotoxicants. Neurotoxicity studies in nonhuman primates (NHP) are used to evaluate the neurotoxicity of small-molecule drugs or vaccines that may affect the nervous system across the blood-brain barrier during preclinical safety assessment. Toxicologic pathological evaluation or neuropathological examination is the "gold standard" for the evaluation of drug neurotoxicity in preclinical drug safety studies. In this paper, the majory factors influencing the quality of neuropathology evaluation in toxicology, including the general strategy of neuropathology evaluation, the optimal timing of evaluation, the specific blood-brain barrier in the nervous system, the method of sampling in the histopathology of nerve tissue, and the interference of artificial artifacts in diagnosis of neuropathology, were detailly analyzed in order to provide a reference for setting guidelines of neurotoxicity risk assessment in China and pathologists and toxicologists engaged in nonclinical neurotoxicity studies.