The DOI matches its Crossref record; 52 of the 53 references it cites were found in a registry or an index.
Effects of Antemortem and Postmortem Variables on Human Brain mRNA Quality: A BrainNet Europe Study
Abstract
Well-characterized and preserved human brain tissue that is prepared and stored in brain banks is an essential resource for research in neurological diseases. This study examined the quality of human brain postmortem tissue from multiple laboratories within the BrainNet Europe brain bank network to identify all possible confounding variables and determine how they may affect RNA quality. Antemortem and postmortem information was retrospectively collected for a large cohort of samples. Total RNA was isolated from anatomically defined brain regions using a standardized procedure; RNA quality was assessed using an Agilent 2100 Bioanalyzer. No significant difference in RNA quality was observed in 6 different brain regions. RNA quality deteriorated with increasing numbers of antemortem events such as hospitalization, coma, respiratory illness, and the use of artificial ventilation; accumulation of such events was associated with elevated hypoxia-inducible factor 1 alpha mRNA expression. Brain pH was found to be a good indicator of RNA quality. There was no correlation of postmortem delay with cerebrospinal fluid pH or RNA quality overall, but some individual RNAs decreased in quality with antemortem events and with postmortem delay. RNA quality did not affect total RNA yield. Determining the factors that are best predictors of RNA quality can help brain banks with selection criteria for storing high-quality brain tissue for research.
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“Additionally, very few transcriptomic studies provide information on acute premortem variables or cause of death, which are particularly important as they may potentially have a much larger effect on RNA quality and gene expression71–76,78–80.”
From Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain (2022) · cites this paper as [76]
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“These findings confirm that highly pure populations of microglia were collected and that PMD had little effect on gene expression.”
From Transcriptomic analysis of purified human cortical microglia reveals age-associated changes (2017) · cites this paper as [20]
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Metadata
- Authors
- Durrenberger, P. F., Fernando, S., Kashefi, S. N., Ferrer, I., Hauw, J.-J., Seilhean, D., Smith, C., Walker, R., Al-Sarraj, S., Troakes, C., Palkovits, M., Kasztner, M., Huitinga, I., Arzberger, T., Dexter, D. T., Kretzschmar, H., & Reynolds, R.
- Affiliations
- Imperial College London (GB)
- Université Pierre-et-Marie-Curie (FR)
- University of Edinburgh (GB)
- King's College London (GB)
- Semmelweis University (HU)
- Netherlands Brain Bank (NL)
- Institut für Neuropathologie (DE)
- Corresponding author
- Durrenberger, Pascal F.
- ORCID
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-01
- Volume
- 69
- Issue
- 1
- Pages
- 70-81
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W2148650719
- Cited by
- 161
- References
- 53
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 10 · 2023: 1 · 2022: 6 · 2021: 13 · 2020: 7 · 2019: 10 · 2018: 13 · 2017: 10 · 2016: 9 · 2015: 12 · 2014: 12 · 2013: 14 · 2012: 13
- FWCI
- 4.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion)
- Funders
- Parkinson's UK (G0909)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Molecular Biology Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- human brain tissue, RNA quality, brain banks, postmortem delay, brain pH, hypoxia-inducible factor-1α, cerebrospinal fluid pH, brain regions, RNA yield
- MeSH terms
- Aged, Aged, 80 and over, Brain, Europe, Female, Humans, Male, Middle Aged, Nervous System Diseases, Organ Preservation, Postmortem Changes, RNA, Messenger, Time Factors, Tissue Banks, Cohort Studies, Linear Models, Reverse Transcriptase Polymerase Chain Reaction
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