In vivo multiphoton microscopy of microvasculature and inflammation: Lessons from the brain and a look at the heart
Abstract
In vivo multiphoton microscopy enables the visualization of dynamics at the cellular scale and is an ideal tool for studying the interactions of cells in vivo. Such imaging has revealed the importance of maintaining vascular health, even in the smallest blood vessels and the capillary bed. In an example in the brain, we found in mouse models of Alzheimer’s disease (AD), that stalled blood flow in a small number of capillaries caused by neutrophils plugs had a surprisingly large effect on total blood flow. Rescue of blood flow led to rapid improvements in short-term memory. We also used laser-induced lesions to study the effects of small-vessel occlusions on inflammation and on amyloid-beta deposits. We discovered rapid alterations in plaques, both dissolution and increase in deposits, that were previously thought to be stable structures. We recently adapted these experimental capabilities to organs with motion including the heart. In models of heart failure, intravital imaging of cardiac vasculature suggests that leukocyte obstruction of capillaries may play a role in the disease. Intravital vital imaging also enables measurements of calcium dynamics and contraction in cardiomyocytes and concurrent dynamics in inflammatory cells.
Biography
Nozomi Nishimura is an Associate Professor in the Meinig School of Biomedical Engineering at Cornell University and develops optical tools for studying in vivo cell behaviors in disease. Her PhD is in physics from the University of California at San Diego with Prof. David Kleinfeld where she studied blood flow in the brain of rodents and developing laser-based models of small stroke. She came to Biomedical Engineering at Cornell in 2006 to do a postdoc with Prof. Chris Schaffer and later joined the faculty in 2013.To study the complex actions of cells in vivo, her lab develops intravital multiphoton microscopy imaging methods that reveal how cells function, move and interact. Injury triggers the recruitment and activation of many immune and inflammatory cell types that, together with the local cells, determine the course of the disease progression. The goal is to develop methods to visualize all of these cells at once and quantify cell actions and function. She applies these tools in many systems, but has particular interests in studying the effects of microvascular dysfunction in the brain. Her lab studies the role of microvascular occlusions in Alzheimer’s disease and neurodegeneration. These methods were recently adapted for the beating mouse heart providing new capabilities to study single cell function and cardiac microvasculature. Recent work expanding into the intestine revealed novel behaviors such as motion and force actuation by stem cells in response to injury.
Sponsored by the Berns Family LAser and Microbeam Program
Sponsored by the Michael and Roberta Berns Laser Microbeam Program
