Nerve agents (NAs) produce acute and long‐term brain injury and dysfunction, as evident from the Japan and Syria incidents. Magnetic resonance imaging (MRI) is a versatile technique to examine such chronic anatomical, functional, and neuronal damage in the brain. The objective of this study was to investigate long‐term structural and neuronal lesion abnormalities in rats exposed to acute soman intoxication. T2‐weighted MRI images of 10 control and 17 soman‐exposed rats were acquired using a Siemens MRI system at 90 days after soman exposure. Quantification of brain tissue volumes and T2 signal intensity was conducted using the Inveon Research Workplace software and the extent of damage was correlated with histopathology and cognitive function. Soman‐exposed rats showed drastic hippocampal atrophy with neuronal loss and reduced hippocampal volume (HV), indicating severe damage, but had similar T2 relaxation times to the control group, suggesting limited scarring and fluid density changes despite the volume decrease. Conversely, soman‐exposed rats displayed significant increases in lateral ventricle volumes and T2 times, signifying strong cerebrospinal fluid expansion in compensation for tissue atrophy. The total brain volume, thalamic volume, and thalamic T2 time were similar in both groups, however, suggesting that some brain regions remained more intact long‐term after soman intoxication. The MRI neuronal lesions were positively correlated with the histological markers of neurodegeneration and neuroinflammation 90 days after soman exposure. The predominant MRI hippocampal atrophy (25%) was highly consistent with massive reduction (35%) of neuronal nuclear antigen–positive (NeuN+) principal neurons and parvalbumin‐positive (PV+) inhibitory interneurons within this brain region. The HV was significantly correlated with both inflammatory markers of GFAP+ astrogliosis and IBA1+ microgliosis. The reduced HV was also directly correlated with significant memory deficits in the soman‐exposed cohort, confirming a possible neurobiological basis for neurological dysfunction. Together, these findings provide powerful insight on long‐term region‐specific neurodegenerative patterns after soman exposure and demonstrate the feasibility of in vivo neuroimaging to monitor neuropathology, predict the risk of neurological deficits, and evaluate response to medical countermeasures for NAs.

中文翻译：

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神经毒剂梭曼暴露后长期神经病理学的磁共振成像分析：与组织病理学和神经功能障碍的相关性

从日本和叙利亚事件中可以明显看出，神经毒剂 (NAs) 会产生急性和长期脑损伤和功能障碍。磁共振成像 (MRI) 是一种多功能技术，可用于检查大脑中的这种慢性解剖、功能和神经元损伤。本研究的目的是调查暴露于急性梭曼中毒的大鼠的长期结构和神经元损伤异常。在 soman 暴露后 90 天，使用 Siemens MRI 系统获取 10 只对照和 17 只 soman 暴露大鼠的 T2 加权 MRI 图像。使用 Inveon Research Workplace 软件对脑组织体积和 T2 信号强度进行量化，并且损伤程度与组织病理学和认知功能相关。暴露于 Soman 的大鼠表现出严重的海马萎缩，神经元丢失和海马体积 (HV) 减少，表明严重损伤，但 T2 弛豫时间与对照组相似，表明尽管体积减少，但疤痕和液体密度变化有限。相反，暴露于索曼的大鼠侧脑室容积和 T2 时间显着增加，表明脑脊液强烈膨胀以补偿组织萎缩。然而，两组的总脑容量、丘脑容量和丘脑 T2 时间相似，但这表明某些脑区在索曼中毒后长期保持更完整。暴露于索曼 90 天后，MRI 神经元病变与神经变性和神经炎症的组织学标志物呈正相关。主要的 MRI 海马萎缩 (25%) 与该大脑区域内神经元核抗原阳性 (NeuN+) 主要神经元和小清蛋白阳性 (PV+) 抑制性中间神经元的大量减少 (35%) 高度一致。HV 与 GFAP+ 星形胶质细胞增生和 IBA1+ 小胶质细胞增生的炎症标志物显着相关。降低的 HV 也与暴露于 soman 的队列中的显着记忆缺陷直接相关，证实了神经功能障碍的可能的神经生物学基础。总之，这些发现为索曼暴露后长期区域特异性神经退行性模式提供了强有力的见解，并证明了体内神经影像学监测神经病理学、预测神经功能缺损风险和评估对 NA 医学对策的反应的可行性。