A new imaging tool recently developed by researchers at the Institute for Stroke and Dementia Research at Ludwig Maximilians University in Munich may markedly improve our understanding of how brain lesions can lead to the development of chronic diseases such as dementia or epilepsy.
The tool, described in the study “Shrinkage-mediated imaging of entire organs and organisms using uDISCO,” published in Nature Methods, will allow researchers to visualize the entire spinal cord of mice under the microscope and to study the complex cellular network that constitutes the central nervous system (CNS).
Nerve cells extend long projections, called axons, through which they transmit electrical impulses. In many neurons, these projections can extend from the brain stem to as far as the base of the spinal column, and damage to these neurons can affect the function of CNS regions that are remote from the actual site of injury.
Evaluating the entire CNS is crucial for repair strategies following CNS damage. But until recently, screening the entire CNS to address damages induced by traumatic brain damage, stroke, or age-related functional decline was a challenging task.
In recent years, researchers have found ways to turn the organs, and even whole organisms, transparent, which, in combination with fluorescent protein tags, allowed the visualization of complex cellular networks deep inside the organs, without the need for sectioning. However, when the tissues were too large, researchers still had problems in visualizing entire organs.
In this study, researchers developed a novel technique called uDISCO that clears the tissues and reduces their size up to 65 percent compared to their original size, while preserving the fluorescence of the protein tags for several months.
The new technique allowed researchers to visualize entire bodies of adult mice to determine long-distance neuronal projections. In addition, the research team revealed that uDISCO could be used provide information at the level of single cells, suggesting that it can help researchers map the complex neuronal networks in 3D, and understand how these networks are disrupted upon certain CNS lesions, resulting in chronic pathologies.
Also, because all cell types can be specifically labeled with the appropriate fluorescent markers, the new method can be a useful tool in a variety of biomedical settings, including cancer cell detection or providing information on the localization of transplanted stem cells.
“Since it allows individual cells to be localized, the method could be used to detect and characterize metastatic tumors at an earlier stage than is now feasible, or to monitor how stem cells behave in the body following a bone-marrow transplant,” Ali Ertürk, who heads a research group at the Institute for Stroke and Dementia Research at the LMU Medical Center, and the study’s lead author, said in a press release.
The research team is now hoping to assemble an online archive that is available for other researchers, which should help reduce an unnecessary duplication of studies.
