A close-up take a look at human brain tissue utilizing a brand-new method established by Benjamin Creekmore and coworkers. Credit: Benjamin Creekmore.
Improving the method researchers can see the tiny structures of the brain can enhance our understanding of a host of brain illness, like Alzheimer's or numerous sclerosis. Studying these illness is tough and has actually been restricted by precision of offered designs.
To see the tiniest parts of cells, researchers typically utilize a strategy called electron microscopy. Electron microscopy traditionally includes including chemicals and physically cutting the tissue. This method can alter the method the cells and structures look, annoying their natural state, and can restrict resolution.
An option technique, called cryo-electron tomography (cryo-ET), supplies clearer pictures of the brain's tiniest parts in a more native state, nevertheless, it needs freezing. Freezing samples to cryogenic temperature levels should be done thoroughly or ice crystals can form, interfering with the native anatomy.
Brand-new research study by Benjamin Creekmore in Yi-Wei Chang and Edward Lee's laboratories at the University of Pennsylvania reveals a brand-new strategy to study the human brain's ultrastructure. They provide their research study at the 68th Biophysical Society Annual Meeting, held February 10– 14, 2024 in Philadelphia, Pennsylvania.
Creekmore and coworkers acquired brain tissue from autopsies, flash froze it straight on unique grids with liquid ethane, and utilized an effective tool called a xenon plasma focused ion beam (FIB) to cut thin pieces for imaging. This technique permitted them to take a look at the brain tissue in its near-natural state without cutting with a knife blade, including chemicals, or slower freezing, all of which can result in modifications in the structures.
“The most typical method to maintain tissue at a time of autopsy is to put it in a freezer and after that utilize it later on. Letting it freeze gradually and then warming it up and then refreezing it likewise interrupts the tissue. Membranes break and you can lose the typical architecture,” Creekmore described.
One unexpected part of the brand-new approach is that it lets them more quickly and quickly freeze much thicker samples– in the previous samples were restricted to 10 microns utilizing comparable methods. “We had the ability to freeze samples approximately 250 microns thick without ice crystals,” Creekmore stated. The procedure of getting thick samples prepared for high-resolution imaging is much faster than with other strategies. This speed-up can enable analysis of a broader variety of samples.
By using this method to brain tissue from people with Alzheimer's illness, they had the ability to observe undamaged structures within cells, such as tau fibrils, a trademark of Alzheimer's illness, and cellular elements that attempt to break down these fibrils. The group likewise imagined and determined myelin, a sheath that's crucial for nerve function however that breaks down in specific illness, such as several sclerosis.
“Techniques for imaging human tissue traditionally have actually been fairly low resolution and they interrupt the native architecture. We wished to attempt to come up with a manner in which we might design and study brain illness in their natural context,” Creekmore stated.
