Peering inside the skull of a mouse to solve meningit...(ts that begins with leakage of fluid fro...)

Date:12/22/2008

ts that begins with leakage of fluid from blood vessels into the meninges, the protective covering of the brain and spinal cord, followed by swelling, which in turn leads to seizures. "T-cells, which are designed to attack the virus, were thought to be the bad guys, but no one understood the exact cellular dynamics involved in infection-induced seizures," explains Dr. Kim, who did the intravital two-photon microscopic imaging in the study, which will be published in the January 8, 2009, issue of Nature. It appeared online last month.

This sort of overreaction by immune cells, called immunopathology, is a factor in numerous conditions in humans, ranging from allergies and autoimmune diseases to stroke and viral infections.

High-Tech Imaging Shows Cells in Action

As the NYU researchers watched the behavior of the T-cells, they noticed something strange. Rather than attacking cells infected with the virus, the T-cells wandered around, apparently unable to recognize their targets. "Up to a point, the T-cells did everything they should do," Dr. Dustin explains. "They made copies of themselves and migrated to where the virus was, but when they got there, they couldn't do the right thing. At least they didn't do what we expected them to, which was to stick tightly to the infected cells."

Intravital two-photon microscopy employs an oscillating infrared laser yielding high-resolution moving pictures. Immune cells appear as bright green lights in the tissue covering the brain of a living mouse. Using surgical methods perfected by at NYU's Skirball Institute for Biomolecular Medicine by Wen Biao Gan, Ph.D., the microscopy produces time-lapse "movies," capturing activity that is not evident in still images made from slices of tissue viewed on a microscope slide.

"A series of frozen images gave the misleading impression that the T-cells were engaging with the infected cells, but intravital microscopy clearly showed that
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Contact: Lordina Klein Lorindaann.Klein@nyumc.org 212-404-3555 NYU Langone Medical Center / New York University School of Medicine Source:Eurekalert

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