Weber Klaus, Domènech Anna, Kegler Kristel, Kreutzer Robert, Mayoral Francisco José, Okazaki Yoshimasa, Ortega Paula, Polledo Laura, Razinger Tanja, Richard Olivia Kristina, Sanchez Raúl, Warfving Nils, Vallejo Raquel, de Miguel Ricardo
AnaPath Services GmbH, Liestal, Switzerland.
AnaPath Research S.A.U., Barcelona, Spain.
Front Vet Sci. 2024 May 21;11:1378609. doi: 10.3389/fvets.2024.1378609. eCollection 2024.
Death initiates a cascade of physiological and biochemical alterations in organs and tissues, resulting in microscopic changes that challenge the histopathological evaluation. Moreover, the brain is particularly susceptible to artifacts owing to its unique composition and its location within the cranial vault. The aim of this study was to compile and illustrate the microscopic changes in the central nervous system (CNS) of rats subjected to delayed postmortem fixation. It also scrutinizes the influence of exsanguination and cooling methods on the initiation and progression of these alterations. Twenty-four Wistar Han outbred rats (RccHan: WIST) were sacrificed and stored either at room temperature (18-22°C) or under refrigeration (2-4°C). Necropsies were conducted at different time points postmortem (i.e., 0.5 h, 1 h, 4 h, 8 h, 12 h, 24 h, 36 h, 48 h, 7 days and 14 days). Brain sections underwent simultaneous digital evaluation by 14 pathologists until a consensus was reached on terminology, key findings, and intensity levels. Microscopic observations varied among cell types. Glial cells were similarly affected throughout the CNS and showed pericellular halo, chromatin condensation and nuclear shrinkage. Neurons showed two types of postmortem changes as most of them showed progressive shrinkage, cytoplasmic dissolution and karyorrhexis whereas others acquired a dark-neuron-like appearance. Neuronal changes showed marked differences among neuroanatomical locations. Additional postmortem changes encompassed: granulation and microcavitation in neuropil and white matter; retraction spaces; detachment of ependyma, choroid plexus, and leptomeninges. Severity of findings after 48 h at room temperature was higher than after seven days under refrigeration and similar to or slightly lower than after 14 days under refrigeration. No clear differences were observed related to the sex or weight of the animals or their exsanguination status. This work elucidates the onset and progression of autolytic changes in the brains of Wistar Han rats, offering insights to accurately identify and enhance the histopathological evaluation.
死亡会引发器官和组织中一系列生理和生化改变，导致微观变化，这对组织病理学评估构成挑战。此外，由于大脑独特的组成结构及其在颅腔内的位置，它特别容易出现人为假象。本研究的目的是汇编并展示延迟尸检固定后大鼠中枢神经系统（CNS）的微观变化。同时，本研究还仔细审查了放血和冷却方法对这些改变的起始和进展的影响。处死24只Wistar Han远交系大鼠（RccHan: WIST），并将其储存在室温（18 - 22°C）或冷藏（2 - 4°C）环境中。在不同的死后时间点（即0.5小时、1小时、4小时、8小时、12小时、24小时、36小时、48小时、7天和14天）进行尸检。14名病理学家对脑切片进行同步数字评估，直至就术语、关键发现和强度水平达成共识。微观观察结果因细胞类型而异。整个中枢神经系统中的胶质细胞受到类似影响，表现为细胞周围晕圈、染色质凝聚和核固缩。神经元呈现出两种死后变化，大多数神经元表现为渐进性萎缩、细胞质溶解和核碎裂，而其他神经元则呈现出暗神经元样外观。神经元变化在神经解剖位置之间存在显著差异。额外的死后变化包括：神经纤维网和白质中的颗粒形成和微空泡化；退缩间隙；室管膜、脉络丛和软脑膜的脱离。室温下48小时后的发现严重程度高于冷藏7天后的情况，与冷藏14天后的情况相似或略低。未观察到与动物性别、体重或放血状态相关的明显差异。这项工作阐明了Wistar Han大鼠大脑自溶变化的起始和进展，为准确识别和加强组织病理学评估提供了见解。
