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      The Sun Health Research Institute Brain Donation Program: Description and Eexperience, 1987–2007

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          Abstract

          The Brain Donation Program at Sun Health Research Institute has been in continual operation since 1987, with over 1000 brains banked. The population studied primarily resides in the retirement communities of northwest metropolitan Phoenix, Arizona. The Institute is affiliated with Sun Health, a nonprofit community-owned and operated health care provider. Subjects are enrolled prospectively to allow standardized clinical assessments during life. Funding comes primarily from competitive grants. The Program has made short postmortem brain retrieval a priority, with a 2.75-h median postmortem interval for the entire collection. This maximizes the utility of the resource for molecular studies; frozen tissue from approximately 82% of all cases is suitable for RNA studies. Studies performed in-house have shown that, even with very short postmortem intervals, increasing delays in brain retrieval adversely affect RNA integrity and that cerebrospinal fluid pH increases with postmortem interval but does not predict tissue viability.

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          Most cited references52

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          Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI.

          We have used restriction isotyping (restriction enzyme isoform genotyping) for rapid typing of common apolipoprotein E isoforms (E2, E3, E4). ApoE restriction isotyping used oligonucleotides to amplify apolipoprotein E gene sequences containing amino acid positions 112 and 158. The amplification products were digested with HhaI and subjected to electrophoresis on polyacrylamide gels. Each of the isoforms was distinguished by a unique combination of HhaI fragment sizes that enabled unambiguous typing of all homozygotic and heterozygotic combinations. HhaI cleaves at GCGC encoding 112arg (E4) and 158arg (E3, E4), but does not cut at GTGC encoding 112cys (E2, E3) and 158cys (E2).
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            Stereological methods for estimating the total number of neurons and synapses: issues of precision and bias.

            Bruce West (1999)
            The emergence of a new generation of stereological techniques for counting objects in histological sections has prompted a debate about whether or not these methods are better than previously available techniques when they are used to make estimates of the total numbers of neurons and synapses in a neural structure. During this debate, the concepts of an unbiased estimate and that of a precise estimate have often been confused. A full understanding of the distinction between these two separate aspects of an estimate is required in order to be able to appreciate the virtues of these new counting methods and to apply them correctly. This review intends to make the fundamental issues of this debate more clear, and describes (1) the fundamental differences between the newer design-based counting techniques and previously available assumption-based techniques, and (2) the distinction between an unbiased estimate and a precise estimate.
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              Human postmortem tissue: what quality markers matter?

              Postmortem human brain tissue is used for the study of many different brain diseases. A key factor in conducting postmortem research is the quality of the tissue. Unlike animal tissue, whose condition at death can be controlled and influenced, human tissue can only be collected naturalistically. This introduces potential confounds, based both on pre- and postmortem conditions, that may influence the quality of tissue and its ability to yield accurate results. The traditionally recognized confounds that reduce tissue quality are agonal factors (e.g., coma, hypoxia, hyperpyrexia at the time of death), and long postmortem interval (PMI). We measured tissue quality parameters in over 100 postmortem cases collected from different sources and correlated them with RNA quality (as indicated by the RNA Integrity Number (RIN)) and with protein quality (as measured by the level of representative proteins). Our results show that the most sensible indicator of tissue quality is RIN and that there is a good correlation between RIN and the pH. No correlation developed between protein levels and the aforementioned factors. Moreover, even when RNA was degraded, the protein levels remained stable. However, these correlations did not prove true under all circumstances (e.g., thawed tissue, surgical tissue), that yielded unexpected quality indicators. These data also suggest that cases whose source was a Medical Examiner's office represent high tissue quality.
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                Author and article information

                Contributors
                thomas.beach@sunhealth.org
                Journal
                Cell Tissue Bank
                Cell and Tissue Banking
                Springer Netherlands (Dordrecht )
                1389-9333
                1573-6814
                18 March 2008
                September 2008
                : 9
                : 3
                : 229-245
                Affiliations
                Sun Health Research Institute, Sun City, 85351 USA
                Article
                9067
                10.1007/s10561-008-9067-2
                2493521
                18347928
                bd5b9798-78c5-49cc-97ff-202186e71145
                © The Author(s) 2008
                History
                : 23 August 2007
                : 8 November 2007
                Categories
                Article
                Custom metadata
                © Springer Science+Business Media B.V. 2008

                postmortem interval,postmortem,cerebrospinal fluid,rna,autopsy,ph,tissue banking,neuropathology,brain banking

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