pH measurement as quality control on human post mortem brain tissue: a study of the BrainNet Europe consortium

Abstract

Aims Most brain diseases are complex entities. Although animal models or cell culture experiments mimic some disease aspects, human post mortem brain tissue remains essential to advance our understanding of brain diseases using biochemical and molecular techniques. Post mortem artefacts must be properly understood, standardized, and either eliminated or factored into such experiments. Here we examine the influence of several premortem and post mortem factors on pH, and discuss the role of pH as a biochemical marker for brain tissue quality. Methods We assessed brain tissue pH in 339 samples from 116 brains provided by 8 different European and 2 Australian brain bank centres. We correlated brain pH with tissue source, post mortem delay, age, gender, freezing method, storage duration, agonal state and brain ischaemia. Results Our results revealed that only prolonged agonal state and ischaemic brain damage influenced brain tissue pH next to repeated freeze/thaw cycles. Conclusions pH measurement in brain tissue is a good indicator of premortem events in brain tissue and it signals limitations for post mortem investigations.

RNA-Seq and human complex diseases: recent accomplishments and future perspectives

“…23,24 However, although promising, the clear difficulties in obtaining brain tissue and the fragile nature of isolated RNA render transcriptome studies quite difficult. 25,26 Microarray analysis, widely used for ND and neuropsychiatric disorders, provided much information about the transcriptional profiles in pathological states, [27][28][29] although discordant results have been often reported. The lack of convergence could be attributed to microarray drawbacks (discussed in 8,9,15 ), as well as to the variable quality/integrity of RNAs strictly influenced by pH, 25 which may dramatically alter the binding to the nucleotide probes, affecting the measure of gene expression levels.…”

“…25,26 Microarray analysis, widely used for ND and neuropsychiatric disorders, provided much information about the transcriptional profiles in pathological states, [27][28][29] although discordant results have been often reported. The lack of convergence could be attributed to microarray drawbacks (discussed in 8,9,15 ), as well as to the variable quality/integrity of RNAs strictly influenced by pH, 25 which may dramatically alter the binding to the nucleotide probes, affecting the measure of gene expression levels. As ND patients have prolonged agonal state in brain tissue (strongly correlated with pH alterations), differences in RNA integrity may -at some extent -account for aberrant gene expression profiles.…”

Translational Research in Pediatrics IV: Solid Tissue Collection and Processing

“…178,233,236,277 The pH of the tissue can be directly correlated with 8 Iodine uptake method Plasmalogens, plasmenyethanolamine, and plasmenylcholine detection 224 DIGE, polyacrylamide gel electrophoresis; ELISA, enzyme-linked immunosorbent assay; HPLC, high-pressure liquid chromatography; ICPMS, inductively coupled plasma mass spectrometry; IHC, immunohistochemistry.…”

“…A prolonged terminal phase is associated with a significantly lower brain pH compared with that of rapid death. 178 Subjects with pH ≤5.9 exhibit specific changes in gene expression. 236 Tissue pH does not correlate with PMI, time in storage, freezing method, or tissue packing, but it can be influenced by gender.…”

“…10,68 The use of postmortem tissue is often hampered, however, by agonal factors, postmortem intervals (PMIs), and storage conditions that contribute to tissue degradation. 177,178 Solid tissues can be derived from living patient organ donors, as well as from deceased patients, resulting from neurologic or cardiac death. [179][180][181][182][183] Recovery of donor medical information before the donor tissue procurement is ideal, 184 particularly in preregistered cases, and it can be supplemented with archived medical records.…”