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

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.

[1]  R. Yolken,et al.  Multivariate analysis of RNA levels from postmortem human brains as measured by three different methods of RT-PCR , 1997, Journal of Neuroscience Methods.

[2]  B. Winblad,et al.  The patients dying after long terminal phase have acidotic brains; implications for biochemical measurements on autopsy tissue , 2005, Journal of Neural Transmission.

[3]  J. Hardy,et al.  A Comparison of Methodologies for the Study of Functional Transmitter Neurochemistry in Human Brain , 1988, Journal of neurochemistry.

[4]  B. Winblad,et al.  How to run a brain bank: potentials and pitfalls in the use of human post-mortem brain material in research. , 1993, Journal of neural transmission. Supplementum.

[5]  R. Anderson,et al.  Intracellular Brain pH, Indicator Tissue Perfusion, Electroencephalography, and Histology in Severe and Moderate Focal Cortical Ischemia in the Rabbit , 1986, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[6]  R. Chuaqui,et al.  Histologic Assessment of the Age of Recent Brain Infarcts in Man , 1993, Journal of neuropathology and experimental neurology.

[7]  R. Busto,et al.  The dissociation of cerebral blood flow, metabolism, and function in the early stages of developing cerebral infarction , 1980, Annals of neurology.

[8]  Robert E. Anderson,et al.  Acidic Foci Within the Ischemic Penumbra of the New Zealand White Rabbit , 1993, Stroke.

[9]  M. Barrachina,et al.  Brain banks: benefits, limitations and cautions concerning the use of post-mortem brain tissue for molecular studies , 2008, Cell and Tissue Banking.

[10]  J. Hardy,et al.  Agonal status affects the metabolic activity of nerve endings isolated from postmortem human brain. , 1985, Neurochemical pathology.

[11]  Paul J. Harrison,et al.  Terminal coma affects messenger RNA detection in post mortem human temporal cortex. , 1991, Brain research. Molecular brain research.

[12]  R. Ross,et al.  Brain pH has a significant impact on human postmortem hippocampal gene expression profiles , 2006, Brain Research.

[13]  Paul J. Harrison,et al.  The relative importance of premortem acidosis and postmortem interval for human brain gene expression studies: selective mRNA vulnerability and comparison with their encoded proteins , 1995, Neuroscience Letters.

[14]  Carol A. Tamminga,et al.  Human postmortem tissue: What quality markers matter? , 2006, Brain Research.

[15]  C. Finch,et al.  Extensive postmortem stability of RNA from rat and human brain , 1986, Journal of neuroscience research.

[16]  N. Cairns,et al.  Quantifying mRNA in postmortem human brain: influence of gender, age at death, postmortem interval, brain pH, agonal state and inter-lobe mRNA variance. , 2003, Brain research. Molecular brain research.

[17]  P. Mangin,et al.  DNA fingerprinting from tissues after variable postmortem periods. , 1993, Journal of forensic sciences.

[18]  L. Iversen,et al.  DIFFERENTIAL EFFECTS OF AGONAL STATUS ON MEASUREMENTS OF GABA AND GLUTAMATE DECARBOXYLASE IN HUMAN POST‐MORTEM BRAIN TISSUE FROM CONTROL AND HUNTINGTON'S CHOREA SUBJECTS , 1979, Journal of neurochemistry.

[19]  C. Yates,et al.  Enzyme Activities in Relation to pH and Lactate in Postmortem Brain in Alzheimer‐Type and Other Dementias , 1990, Journal of neurochemistry.

[20]  C D Marsden,et al.  Tissue pH as an indicator of mRNA preservation in human post-mortem brain. , 1995, Brain research. Molecular brain research.

[21]  Paul J. Harrison,et al.  Pre‐and Postmortem Influences on Brain RNA , 1993, Journal of neurochemistry.

[22]  R. Anderson,et al.  Brain acidosis, cerebral blood flow, capillary bed density, and mitochondrial function in the ischemic penumbra. , 1999, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[23]  E. Perry,et al.  The influence of agonal status on some neurochemical activities of postmortem human brain tissue , 1982, Neuroscience Letters.

[24]  D. Goldstein,et al.  Postmortem Delay Has Minimal Effect on Brain RNA Integrity , 2007, Journal of neuropathology and experimental neurology.

[25]  W. Paschen,et al.  Lactate and pH in the Brain: Association and Dissociation in Different Pathophysiological States , 1987, Journal of neurochemistry.

[26]  R. Ravid,et al.  Brain banking and the human hypothalamus--factors to match for, pitfalls and potentials. , 1992, Progress in brain research.