Global Pathology and Investigative Toxicology, Pfizer Inc, Groton, CT, USA.
Department of Statistics, Pfizer Inc, Cambridge, MA, USA.
Toxicol Pathol. 2020 Jul;48(5):694-701. doi: 10.1177/0192623320926475. Epub 2020 Jun 1.
Axonal dystrophy (AD) is a common age-related neurohistological finding in vertebrates that can be congenital or induced by xenobiotics, vitamin E deficiency, or trauma/compression. To understand the incidence and location of AD as a background finding in Beagle dogs used in routine toxicity studies, we examined central nervous system (CNS) and selected peripheral nervous system (PNS) tissues in twenty 18- to 24-month-old and ten 4- to 5-year-old control males and females. Both sexes were equally affected. The cuneate, gracile, and cochlear nuclei and the cerebellar white matter (rostral vermis) were the most common locations for AD. Incidence of AD increased with age in the cuneate nucleus, cerebellar white matter (rostral vermis), trigeminal nuclei/tracts, and lumbar spinal cord. Axonal dystrophy in the CNS was not accompanied by neuronal degeneration/necrosis, nerve fiber degeneration, and/or glial reaction. Axonal dystrophy was not observed in the PNS (sciatic nerve, vagus nerve branches, or gastrointestinal mural autonomic plexuses).
轴突变性(AD)是脊椎动物中一种常见的与年龄相关的神经组织学发现,可由先天因素或外源性物质、维生素 E 缺乏、创伤/压迫引起。为了了解 AD 在常规毒性研究中使用的比格犬作为背景发现的发生率和位置,我们检查了中枢神经系统(CNS)和选定的周围神经系统(PNS)组织,这些组织来自 20 只 18-24 个月大和 10 只 4-5 岁的雄性和雌性对照犬。两种性别的犬均受到同等影响。楔束核、薄束核和耳蜗核以及小脑白质(蚓部)是 AD 最常见的部位。AD 的发生率在楔束核、小脑白质(蚓部)、三叉神经核/束和腰椎脊髓中随年龄增长而增加。CNS 中的轴突变性不伴有神经元变性/坏死、神经纤维变性和/或神经胶质反应。PNS(坐骨神经、迷走神经分支或胃肠道壁自主神经丛)中未观察到轴突变性。