Temporal Sequence of Autolysis in the Cerebellar Cortex of the Mouse

We explored the involvement of the lectin pathway of complement in post-traumatic brain injury (TBI) pathophysiology in humans. Brain samples were obtained from 28 patients who had undergone therapeutic contusion removal, within 12 h (early) or from >12 h until five days (late) from injury, and from five non-TBI patients. Imaging analysis indicated that lectin pathway initiator molecules (MBL, ficolin-1, ficolin-2 and ficolin-3), the key enzymes MASP-2 and MASP-3, and the downstream complement components (C3 fragments and TCC) were present inside and outside brain vessels in all contusions. Only ficolin-1 was found in the parenchyma of non-TBI tissues. Immunoassays in brain homogenates showed that MBL, ficolin-2 and ficolin-3 increased in TBI compared to non-TBI (2.0, 2.2 and 6.0-times) samples. MASP-2 increased with subarachnoid hemorrhage and abnormal pupil reactivity, two indicators of structural and functional damage. C3 fragments and TCC increased, respectively, by 3.5 - and 4.0-fold in TBI compared to non-TBI tissue and significantly correlated with MBL, ficolin-2, ficolin-3, MASP-2 and MASP-3 levels in the homogenates. In conclusion, we show for the first time the direct presence of lectin pathway components in human cerebral contusions and their association with injury severity, suggesting a central role for the lectin pathway in the post-traumatic pathophysiology of human TBI.

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“…However, the neuronal structures (targets of iC3b/C3b and TCC) are known to be preserved till 48 h post mortem. 56…”

Section: Discussionmentioning

confidence: 99%

Human brain trauma severity is associated with lectin complement pathway activation

Blasio

Fumagalli

Orsini

et al. 2018

J Cereb Blood Flow Metab

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“…The nomenclature proposed in the present work to characterize postmortem findings reflects a shared consensus among the 14 pathologists evaluating the slides. The terminology chosen aims to be simple and descriptive, applying whenever possible pre-existing terms already established in the pathology literature and avoiding the use of specific diagnostic terms ( 7 , 8 , 10 , 16 , 18 , 19 ). Some terms employed in the present work (i.e., chromatin condensation, nuclear shrinkage, nuclear fading) reflect histological features that are also found in physiologic and pathologic processes of cell degeneration and/or cell death (e.g., pyknosis is evinced by chromatin condensation and shrinking; karyolysis is characterized by nuclear fading due to the action of endonucleases) ( 20–22 ).…”

Section: Discussionmentioning

confidence: 99%

Onset and progression of postmortem histological changes in the central nervous system of RccHan™: WIST rats

Weber,

Domènech,

Kegler

et al. 2024

Front. Vet. Sci.

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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.

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“…The main brain region that has been associated with a faster rate of postmortem decomposition is the cerebellum (Averback, 1980;Furukawa et al, 2015;Finnie et al, 2016).…”

Section: Brain Region and Cell Type Heterogeneitymentioning

confidence: 99%

“…Arsénio-Nunes 1973 describe pronounced astrocyte process swelling in the molecular layer and at the level of vascular end feet at 30 min PMI (Arsénio-Nunes et al, 1973). Finnie 2016 reported that Bergmann glia had cytoplasmic swelling much earlier than Purkinje cells in the PMI (Finnie et al, 2016). Del Bigio 2000 describe pronounced swelling of astrocytes and oligodendrocytes during the PMI that could be spatially associated with a hemorrhagic lesion prior to death (Del Bigio et al, 2000).…”

Section: Alterations In Cellular and Subcellular Volumesmentioning

confidence: 99%

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Postmortem changes in brain cell structure: a review

Krassner¹,

Kauffman²,

Sowa³

et al. 2023

Preprint

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Brain cell structure is a key determinant of neural function that is frequently altered in neurobiological disorders. Following the global loss of blood flow to the brain that initiates the postmortem interval (PMI), cells rapidly become depleted of energy and begin to decompose. To ensure that our methods for studying the brain using autopsy tissue are robust and reproducible, there is a critical need to delineate the expected changes in brain cell morphometry during the PMI. We searched multiple databases to identify studies measuring the effects of PMI on the morphometry (i.e. external dimensions) of brain cells. We screened 2119 abstracts, 361 full texts, and included 172 studies. Mechanistically, fluid shifts causing cell volume alterations and vacuolization is an early event in the PMI, while loss of cell membrane visualization altogether is a later event. Decomposition rates are highly heterogenous and depend on the methods for visualization, the structural feature of interest, and modifying variables such as the storage temperature or the species. Geometrically, deformations of cell membranes are common early events that initiate within minutes. On the other hand, topological relationships between cellular features appear to be intact for more extended periods. Taken together, there is an uncertain length of time, usually ranging from several hours to several days, over which cell membrane structure is progressively lost. This review may be helpful for investigators studying human postmortem brain tissue, wherein the PMI is an unavoidable aspect of the research.

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Temporal Sequence of Autolysis in the Cerebellar Cortex of the Mouse

Cited by 5 publications

References 12 publications

Human brain trauma severity is associated with lectin complement pathway activation

Human brain trauma severity is associated with lectin complement pathway activation

Onset and progression of postmortem histological changes in the central nervous system of RccHan™: WIST rats

Postmortem changes in brain cell structure: a review

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