Perfusion fixation in brain banking: a systematic review

Acta Neuropathologica Communications - Tập 7 - Trang 1-26 - 2019
Whitney C. McFadden1, Hadley Walsh2, Felix Richter3, Céline Soudant4, Clare H. Bryce2, Patrick R. Hof5,6, Mary Fowkes2, John F. Crary2,5,6,7, Andrew T. McKenzie1,7
1Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA
2Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, USA
3Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, USA
4Gustave L. and Janet W. Levy Library, Mount Sinai Health System, New York, USA
5Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, USA
6Friedman Brain Institute and Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai, New York, USA
7Neuropathology Brain Bank and Research CoRE, Icahn School of Medicine at Mount Sinai, New York, USA

Tóm tắt

Perfusing fixatives through the cerebrovascular system is the gold standard approach in animals to prepare brain tissue for spatial biomolecular profiling, circuit tracing, and ultrastructural studies such as connectomics. Translating these discoveries to humans requires examination of postmortem autopsy brain tissue. Yet banked brain tissue is routinely prepared using immersion fixation, which is a significant barrier to optimal preservation of tissue architecture. The challenges involved in adopting perfusion fixation in brain banks and the extent to which it improves histology quality are not well defined. We searched four databases to identify studies that have performed perfusion fixation in human brain tissue and screened the references of the eligible studies to identify further studies. From the included studies, we extracted data about the methods that they used, as well as any data comparing perfusion fixation to immersion fixation. The protocol was preregistered at the Open Science Framework: https://osf.io/cv3ys/ . We screened 4489 abstracts, 214 full-text publications, and identified 35 studies that met our inclusion criteria, which collectively reported on the perfusion fixation of 558 human brains. We identified a wide variety of approaches to perfusion fixation, including perfusion fixation of the brain in situ and ex situ, perfusion fixation through different sets of blood vessels, and perfusion fixation with different washout solutions, fixatives, perfusion pressures, and postfixation tissue processing methods. Through a qualitative synthesis of data comparing the outcomes of perfusion and immersion fixation, we found moderate confidence evidence showing that perfusion fixation results in equal or greater subjective histology quality compared to immersion fixation of relatively large volumes of brain tissue, in an equal or shorter amount of time. This manuscript serves as a resource for investigators interested in building upon the methods and results of previous research in designing their own perfusion fixation studies in human brains or other large animal brains. We also suggest several future research directions, such as comparing the in situ and ex situ approaches to perfusion fixation, studying the efficacy of different washout solutions, and elucidating the types of brain donors in which perfusion fixation is likely to result in higher fixation quality than immersion fixation.

Tài liệu tham khảo

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