Autopsy at 2 months after death: Brain is satisfactorily preserved for neuropathology

Gelpí, Ellen; Preusser, Matthias; Bauer, Gregor; Budka, Herbert

doi:10.1016/j.forsciint.2006.07.017

Cited by 12 publications

(8 citation statements)

References 17 publications

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“…Some macroscopically visible surface deterioration had occurred; histologically, however, normal brain structures were preserved, including all important cell types (neurons, astrocytes, oligodendrocytes, and microglia), neuropil, axons, and myelin sheaths. 17 These studies support the view that, at both the macroscopic and microscopic level, complete ischemia does not result in instantaneous and complete disappearance of brain structure. The process of brain death is a gradual one that begins with the loss of brain ion homeostasis, 18 followed by the cessation of brain metabolism, postmortem up and downregulation of genes, 19 proceeding to the loss of the viability of individual brain organelles.…”

Section: Scientific Backgroundsupporting

confidence: 71%

Ultrastructural Characterization of Prolonged Normothermic and Cold Cerebral Ischemia in the Adult Rat

Wolf¹,

Phaedra²,

Perry

et al. 2020

Rejuvenation Research

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The ultrastructural effects of prolonged normothermic and cold ischemia on the cerebral cortex of the adult rat were investigated. Complete cerebral ischemia was produced by cardiac arrest and the animals' temperature was maintained at 37°C for periods ranging from 0 to 81 hours before electron microscopy preparation. Electron micrographs of cold cerebral ischemia were generated after stabilizing the rat's temperature at 0°C after cardiac arrest for periods ranging from 0 hours to 6 months. A qualitative examination of the electron micrographs shows structural signatures of energy depletion such as vessel leaking and chromatin clumping after 1 hour at 37°C and after 24 hours at 0°C, followed by synapse degradation after 6 hours at 37°C and 1 week at 0°C. Evidence of advanced necrosis was observed after 36 hours at 37°C and 2 months at 0°C. A deep learning algorithm was introduced that demonstrates the temperature dependence of ischemia-induced ultrastructural changes and that can also successfully distinguish between early ischemic changes and advanced necrosis.

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Section: Scientific Backgroundsupporting

confidence: 71%

Ultrastructural Characterization of Prolonged Normothermic and Cold Cerebral Ischemia in the Adult Rat

Wolf¹,

Phaedra²,

Perry

et al. 2020

Rejuvenation Research

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“…It has previously been reported that choice of Ab and use of methodology are of significant importance. The community should be aware of the multitude of issues that influence the staining outcome (fixative, fixation time, storage time of sections) and that this influence varies from one epitope to another (McNicol and Richmond 1998;Shi et al 2001;Gelpi et al 2007;D'Amico et al 2009;Pikkarainen et al 2010a;Karlsson and Karlsson 2011;Kovacs et al 2012). Another issue that the BNE consortium has become aware of is the need for precise detailed instructions.…”

Section: Discussionmentioning

confidence: 99%

“…IHC methodology is prone to considerable variability that might cause differing results, as was elegantly reported by Mackenzie et al (2006b). Today, it is acknowledged that use of the IHC methods requires knowledge and competence both regarding methodology and interpretation of the result obtained (McNicol and Richmond 1998;Shi et al 2001;Gelpi et al 2007;D'Amico et al 2009;Pikkarainen et al 2010a; Karlsson and Karlsson 2011;Kovacs et al 2012). In addition, the agreement rate for the designation of a specific type of a disease by numerous investigators might be less optimal, as previously reported by BrainNet Europe (BNE) (Alafuzoff et al 2008b(Alafuzoff et al , 2009a.…”

Section: Introductionmentioning

confidence: 99%

Neuropathological assessments of the pathology in frontotemporal lobar degeneration with TDP43-positive inclusions: an inter-laboratory study by the BrainNet Europe consortium

et al. 2014

Self Cite

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The BrainNet Europe consortium assessed the reproducibility in the assignment of the type of frontotemporal lobar degeneration (FTLD) with TAR DNA-binding protein (TDP) 43 following current recommendations. The agreement rates were influenced by the immunohistochemical (IHC) method and by the classification strategy followed. p62-IHC staining yielded good uniform quality of stains, but the most reliable results were obtained implementing specific Abs directed against the hallmark protein TDP43. Both assessment of the type and the extent of lesions were influenced by the Abs and by the quality of stain. Assessment of the extent of the lesions yielded poor results repeatedly; thus, the extent of pathology should not be used in diagnostic consensus criteria. Whilst 31 neuropathologists typed 30 FTLD-TDP cases, inter-rater agreement ranged from 19 to 100 per cent, being highest when applying phosphorylated TDP43/IHC. The agreement was highest when designating Type C or Type A/B. In contrast, there was a poor agreement when attempting to separate Type A or Type B FTLD-TDP. In conclusion, we can expect that neuropathologist, independent of his/her familiarity with FTLD-TDP pathology, can identify a TDP43-positive FTLD case. The goal should be to state a Type (A, B, C, D) or a mixture of Types (A/B, A/C or B/C). Neuropathologists, other clinicians and researchers should be aware of the pitfalls whilst doing so. Agreement can be reached in an inter-laboratory setting regarding Type C cases with thick and long neurites, whereas the differentiation between Types A and B may be more troublesome.

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“…Second, insoluble Aß deposits are known to resistant to postmortem tissue/protein degradation. In fact, amyloid pathology can been detected in human brains collected months even years after death [ 117 – 119 ]. On the other hand, histological integrity and biological molecules including normal neural proteins are decomposed rapidly if brain samples are not preserved by tissue fixation on time [ 117 ].…”

Section: Main Textmentioning

confidence: 99%

Can brain impermeable BACE1 inhibitors serve as anti-CAA medicine?

Huang

Liu

et al. 2017

BMC Neurol

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BackgroundCerebral amyloid angiopathy (CAA) is characterized by the deposition of ß-amyloid peptides (Aß) in and surrounding the wall of microvasculature in the central nervous system, together with parenchymal amyloid plaques collectively referred to as cerebral amyloidosis, which occurs in the brain commonly among the elderly and more frequently in patients with Alzheimer’s disease (AD). CAA is associated with vascular injury and may cause devastating neurological outcomes. No therapeutic approach is available for this lesion to date.Main bodyß-Secretase 1 (BACE1) is the enzyme initiating Aß production. Brain permeable BACE1 inhibitors targeting primarily at the parenchymal plaque pathology are currently evaluated in clinical trials. This article presents findings in support of a role of BACE1 elevation in the development of CAA, in addition to plaque pathogenesis. The rationale, feasibility, benefit and strategic issues for developing BACE1 inhibitors against CAA are discussed. Brain impermeable compounds are considered preferable as they might exhibit sufficient anti-CAA efficacy without causing significant neuronal/synaptic side effects.ConclusionEarly pharmacological intervention to the pathogenesis of CAA is expected to provide significant protection for cerebral vascular health and hence brain health. Brain impermeable BACE1 inhibitors should be optimized and tested as potential anti-CAA therapeutics.

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Autopsy at 2 months after death: Brain is satisfactorily preserved for neuropathology

Cited by 12 publications

References 17 publications

Ultrastructural Characterization of Prolonged Normothermic and Cold Cerebral Ischemia in the Adult Rat

Ultrastructural Characterization of Prolonged Normothermic and Cold Cerebral Ischemia in the Adult Rat

Neuropathological assessments of the pathology in frontotemporal lobar degeneration with TDP43-positive inclusions: an inter-laboratory study by the BrainNet Europe consortium

Can brain impermeable BACE1 inhibitors serve as anti-CAA medicine?

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