Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, United States of America.
Department of Radiology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States of America.
PLoS One. 2020 Jan 24;15(1):e0228109. doi: 10.1371/journal.pone.0228109. eCollection 2020.
Irradiation of food at 50-55 kGy results in a profound, chronic demyelinating-remyelinating disease of the entire central nervous system (CNS) in cats, named Feline Irradiated Diet-Induced Demyelination (FIDID). This study examines the early stages of demyelination and long-term consequences of demyelination and remyelination on axon survival or loss. Myelin vacuolation is the primary defect leading to myelin breakdown, demyelination then prompt remyelination in the spinal cord and brain. There is no evidence of oligodendrocyte death. The spinal cord dorsal column is initially spared yet eventually becomes severely demyelinated with subsequent loss of axons in the core and then surface of the fasciculus gracilis. However remyelination of the sub-pial axons in the dorsal column results in their protection. While there was a lack of biochemical evidence of Vitamin B12 deficiency, the pathological similarities of FIDID with sub-acute combined degeneration (SCD) led us to explore treatment with Vitamin B12. Treatment led to recovery or improvement in some cats and neurologic relapse on cessation of B12 therapy. While the reason that irradiated food is myelinotoxic in the cat remains unresolved, nonetheless the neuropathological changes match exactly what is seen in SCD and its models and provide an ideal model to study the cellular and molecular basis of remyelination.
在 50-55kGy 的辐射下,猫的整个中枢神经系统(CNS)会发生一种深刻的、慢性的脱髓鞘-再髓鞘疾病,这种疾病被命名为猫放射诱导饮食性脱髓鞘(FIDID)。本研究检查了脱髓鞘的早期阶段以及脱髓鞘和再髓鞘对轴突存活或丢失的长期后果。髓鞘空泡形成是导致髓鞘破裂的主要缺陷,随后在脊髓和大脑中迅速发生脱髓鞘和再髓鞘。没有证据表明少突胶质细胞死亡。脊髓背柱最初幸免,但最终变得严重脱髓鞘,随后核心和随后的薄束中的轴突丢失。然而,背柱软脑膜下轴突的再髓鞘导致了它们的保护。虽然缺乏维生素 B12 缺乏的生化证据,但 FIDID 与亚急性联合变性(SCD)的病理相似性促使我们探索维生素 B12 的治疗方法。治疗导致一些猫的恢复或改善,以及在停止 B12 治疗后出现神经学复发。虽然导致猫的辐照食物具有髓鞘毒性的原因仍未解决,但神经病理学变化与 SCD 及其模型完全一致,为研究再髓鞘化的细胞和分子基础提供了理想的模型。