神經(jīng)毒性是許多藥物或化合物常見的毒副作用。在新藥研發(fā)早期要進行神經(jīng)毒性篩選。對于可能通過血腦屏障影響神經(jīng)系統(tǒng)的小分子藥物或疫苗類的生物制品在臨床前安全性評價中要進行非人靈長類動物的神經(jīng)毒性評價。毒性病理學(xué)或神經(jīng)病理學(xué)評價是臨床前藥物神經(jīng)毒性評價的金標準。針對影響藥物毒性神經(jīng)病理學(xué)評價質(zhì)量的幾個主要因素，包括神經(jīng)病理學(xué)評價的一般策略、最佳的評價時機、特殊的神經(jīng)組織屏障系統(tǒng)、神經(jīng)組織病理制片中的取材方法以及人工假象對神經(jīng)病理學(xué)診斷的干擾，進行詳細的解析，以期為我國神經(jīng)毒性評價指導(dǎo)原則的制定和藥物非臨床神經(jīng)毒性研究提供參考。

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.

十二五國家科技重大專項（2015ZX09501004-002，2015ZX09501007-004）