Peering Inside the Skull of a Mouse to Solve Meningitis Mystery

NYULangoneMedicalCenter scientists and their collaborators at the Scripps Research Institute in La Jolla, Calif., have discovered an unexpected cause for the fatal seizures seen in mice with viral meningitis, an infection of the central nervous system, according to a study published in the journal Nature. The finding may lead to a new way of thinking about how the human immune system responds to viral diseases.

The NYU researchers, Michael L. Dustin, PhD, the Irene Diamond Professor of Immunology and professor of pathology at NYU School of Medicine, and Jiyun V. Kim, PhD, a scientist in Dustin's laboratory, employed intravital two-photon microscopy to peer inside the skulls of infected mice. This breakthrough technology allows scientists to take moving pictures of immune cells in action. The cells are tagged with a protein that glows fluorescent green when activated by infrared light, which is able to penetrate living tissue without damaging it.

Dustin and Kim collaborated with Dorian McGavern, PhD, associate professor of immunology and Silvia Kang, PhD, at Scripps Research Institute, who provided virology expertise and performed many critical experiments that supported the unexpected findings of the study.

The scientists used lymphocytic choriomeningitis virus (LCMV), which is relatively harmless in humans with a healthy immune system. Other viruses that cause meningitis usually are associated with mild symptoms. By contrast, bacterial meningitis is a much more contagious and serious disease, particularly in young children. If not treated promptly with antibiotics, it may lead to hearing loss, brain damage, and even death.

Mice infected with LCMV suffer fatal seizures. It was known that these seizures are not caused by the virus itself, but by the immune system's response to the infection. Something sets off a chain of events 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.