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Next generation histology methods for three-dimensional imaging of fresh and archival human brain tissues

Author

Listed:
  • Hei Ming Lai

    (The University of Hong Kong
    Imperial College London, Burlington Danes Building, Hammersmith Campus)

  • Alan King Lun Liu

    (The University of Hong Kong
    Imperial College London, Burlington Danes Building, Hammersmith Campus)

  • Harry Ho Man Ng

    (The University of Hong Kong)

  • Marc H. Goldfinger

    (Imperial College London, Burlington Danes Building, Hammersmith Campus)

  • Tsz Wing Chau

    (Imperial College London, Burlington Danes Building, Hammersmith Campus)

  • John DeFelice

    (Imperial College London, Burlington Danes Building, Hammersmith Campus)

  • Bension S. Tilley

    (Imperial College London, Burlington Danes Building, Hammersmith Campus)

  • Wai Man Wong

    (The University of Hong Kong)

  • Wutian Wu

    (The University of Hong Kong
    GMH Institute of CNS Regeneration, Jinan University
    Re-Stem Biotechnology Co., Ltd)

  • Steve M. Gentleman

    (Imperial College London, Burlington Danes Building, Hammersmith Campus)

Abstract

Modern clearing techniques for the three-dimensional (3D) visualisation of neural tissue microstructure have been very effective when used on rodent brain but very few studies have utilised them on human brain material, mainly due to the inherent difficulties in processing post-mortem tissue. Here we develop a tissue clearing solution, OPTIClear, optimised for fresh and archival human brain tissue, including formalin-fixed paraffin-embedded material. In light of practical challenges with immunostaining in tissue clearing, we adapt the use of cresyl violet for visualisation of neurons in cleared tissue, with the potential for 3D quantification in regions of interest. Furthermore, we use lipophilic tracers for tracing of neuronal processes in post-mortem tissue, enabling the study of the morphology of human dendritic spines in 3D. The development of these different strategies for human tissue clearing has wide applicability and, we hope, will provide a baseline for further technique development.

Suggested Citation

  • Hei Ming Lai & Alan King Lun Liu & Harry Ho Man Ng & Marc H. Goldfinger & Tsz Wing Chau & John DeFelice & Bension S. Tilley & Wai Man Wong & Wutian Wu & Steve M. Gentleman, 2018. "Next generation histology methods for three-dimensional imaging of fresh and archival human brain tissues," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03359-w
    DOI: 10.1038/s41467-018-03359-w
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    Cited by:

    1. Jingtan Zhu & Xiaomei Liu & Zhang Liu & Yating Deng & Jianyi Xu & Kunxing Liu & Ruiying Zhang & Xizhi Meng & Peng Fei & Tingting Yu & Dan Zhu, 2024. "SOLID: minimizing tissue distortion for brain-wide profiling of diverse architectures," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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