"Transparent Brain" Expected to Yield Breakthroughs in Understanding Neurological Disorders

Replacement of the brain's fat content with a clear, permeable gel allows optical, fluorescent, and electron microscope studies as well as immunohistochemical analyses to be carried out on intact tissues that have not been damaged or modified by sample preparation techniques.

Investigators at Stanford University (Palo Alto, CA, USA) developed a novel method for creating a "transparent" brain by replacing fat tissue with a clear, permeable gel. The technique was based on infusing a cocktail of reagents, including a plastic-like polymer and formaldehyde, into a mouse brain. When heated, the solution formed a transparent, porous gel that biochemically integrated with, and physically supported, the brain tissue while excluding the lipids, which were removed via an electrochemical process. The process was named CLARITY for Clear Lipid-exchanged Anatomically Rigid Imaging/Immunostaining-compatible Tissue Hydrogel.

A report in the April 10, 2013, online edition of the journal Nature revealed initial results obtained with a CLARITY-treated mouse brain. These results showed intact-tissue imaging of long-range projections, local circuit wiring, cellular relationships, subcellular structures, protein complexes, nucleic acids, and neurotransmitters. CLARITY also enabled intact-tissue in situ hybridization, immunohistochemistry with multiple rounds of staining and de-staining in nonsectioned tissue, and antibody labeling throughout the intact adult mouse brain.

In addition, CLARITY enabled fine structural analysis of clinical samples, including nonsectioned human tissue from a formaldehyde-preserved postmortem human brain from a person who had autism, establishing a path for the transmutation of human tissue into a stable, intact, and accessible form suitable for probing structural and molecular underpinnings of physiological function and disease.

“CLARITY will help support integrative understanding of large-scale, intact biological systems,” said senior author Dr. Karl Deisseroth, professor of bioengineering and of psychiatry and behavioral sciences at Stanford University. “It provides access to subcellular proteins and molecules, while preserving the continuity of intact neuronal structures such as long-range circuit projections, local circuit wiring, and cellular spatial relationships.”

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