Whole-brain three-dimensional imaging for quantification of drug targets and treatment effects in mouse models of neurodegenerative diseases
Henrik H. Hansen
Urmas Roostalu
Jacob Hecksher-S?rensen
1.Gubra,H?rsholm,Denmark2.Gubra,H?rsholm,Denmark3.Gubra,H?rsholm,Denmark
摘要:Quantitative histopathology in preclinical neuroscience: Altered brain functionality in neurodegenerative diseases, including Par-kinson's disease (PD) and Alzheimer's disease (AD), involve com-plex pathological changes and molecular mechanisms which poses a major challenge for development of effective drug treatments. Progressive loss of specific neuron types and projections are hall-marks of PD and AD and proper histological evaluation of relevant disease models therefore requires highly reliable cell detection and quantification methods. Immunohistochemistry is the prevail-ing method of choice to visualize and quantify histopathological changes in brain tissue sections. Although stereology applied to se-rially sampled sections is considered the gold standard for unbiased three-dimensional (3D) estimation of histomorphometric changes and therapeutic effects in neurodegeneration models, the elaborate sequence of histological processing steps can be time-intensive and limit analyses to a few preselected brain areas. Whereas physical tis-sue sections may provide higher structural resolution for any given 2D plane, the advantage of volume imaging is to facilitate 3D inves-tigation of brain structures and cell populations in the intact brain. In this respect, clinical whole-brain 3D imaging has continued to provide valuable insights in early detection, diagnosis and interpre-tation of PD and AD in humans, yet it has remained challenging to establish in preclinical research and drug discovery.
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论文发表日期:2020-12-28
在线出版日期:2025-08-15(本平台首次上网日期,不代表文献的发表时间)
页数:3( 2255-2257 )
