The VANJHCS researchers have a great deal of experience investigating the underlying mechanisms and treatments for a variety of disorders afflicting Veterans. Tools have included fluorescent microscopes for immunohistochemistry and immunocytochemistry to determine the locations and changes in important cellular factors. The problem is that essential pathological and restorative mechanisms involve morphological shapes, colocalizations, subcellular associations, etc., unattainable in two dimensions and this is limiting our abilities. To obtain a three dimensional picture of what is really happening with respect to tissues, cells, and organelles, while we search for optimal therapeutic strategies for Veterans, a laser scanning confocal microscope is required. Our facility does not have a confocal capability, although several of our investigators have taken advantage of these systems at previous stations in the past. The instrument sought would excite with lasers for probes in the blue, green, red, and infrared ranges. Emissions, spectrally scanned, would be measured with photomultiplier plus higher sensitivity semiconductor detectors. A motorized stage will enable reproducible positioning and automated collection of multiple fields. Capturing involves a galvanometer driven or a resonance, high speed scanner. Our objectives will include a wide field as well as a high resolution, 1.4 N.A. 60 X oil lens. Some of the specific projects that will be aided by the confocal include Dr. Citron's studies of chronic TBI (Preventing TBI-Induced Chronic Functional Loss with a Neuroprotective Antioxidant) and also Gulf War Veteran's neurodegeneration (Neurodegenerative changes after exposure to Gulf War insults), Dr. Beck's studies of Gulf War Veteran's Illnesses (Neuroinflammation and abnormal behavior following combined chemical exposures and bacterial infection), Parkinson's disease (Volatile organic compound effects on brain and behavior), glucose-inhibited neurons (Role of glucose-inhibited orexin neurons in weight regain following dieting), and also opioid use (Determining the relationship between opioid use and avoidance susceptibility), Dr. Chen's research with melanomas (GRM1-induced HIF-1? and reprogramming of glutamine metabolisms in melanoma), Dr. Dowling?s investigations of dementia and neurodegeneration (Novel EPO peptide therapy for a new mouse model of dementia), demyelinating disease (EPO fragments for demyelinating disease treatment), multiple sclerosis, and brain trauma (Short stabilized EPO-peptide as side-effect free therapeutic agents for multiple sclerosis and acute brain trauma), Dr. Pang's evaluation of opioid effects on synaptic plasticity (Hippocampus, synaptic plasticity and anxiety vulnerability) and his studies of traumatic brain injury (mTBI and brainstem modulatory systems: Implications for impulsivity and reinforcement), Dr. Guo's examinations of bile production (Gut bile acids, Fxr, & Fgf15 in total parenteral nutrition-associated cholestasis) and also of liver disease (Role of FGF15 in liver regeneration). The collective experience within our Research & Development service indicates that our very collaborative group would make excellent use of the three dimensional resolution and quantitative capacities provided by a confocal system to best advance our research.
Our researchers study different disorders that are of particular importance to Veterans and all of these investigators are focused on finding ways to improve the health of this population. The discoveries that have been made have been recognized nationally and internationally and include determinations of normal cellular processes and the alterations that occur that cause health problems for our Veterans. By understanding exactly what is 'broken' in these conditions we have been able to develop methods to repair or compensate to improve outcomes. A confocal microscope capability will allow us to more accurately understand the true three dimensional cellular modulations involved with functional loss and treatment design for traumatic brain injury, chronic traumatic encephalopathy, Alzheimer's disease, ALS, melanoma, liver disease, etc.
