Neurodegenerative disease and stroke continue to be leading causes of morbidity and mortality in the population, and the cost to families, society and the health care system cannot be overestimated. Significant progress has been made in dissecting the molecular pathways leading to synaptic pathology in neurodegenerative disease and post-stroke reorganization. However, translation of these results into clinically effective treatments remains a major challenge for the neurological disease community today.
The progress in translating basic science findings to clinical practice has been significantly compromised by major differences in the level of description of the physiological phenomena in animals and human studies. As such, most of the available data from mouse models of neurological disease reflect single-cell behavior in cell culture or isolated tissue preparations. However, the health of neurons in the intact brain depends not only on neuron-to-neuron connections but on functional interactions among the neurons, capillaries, and glia, termed the "neurovascular unit” (NVU).
Therefore, our major goal is to develop and apply new cutting-edge imaging technology for studying neuronal, vascular and metabolic activity within the NVU in live animal models of human disease. The NVU approach provides a more integrative answer to neurological damage, which may be closer to modeling the clinical reality.
The lessons learned from live NVU imaging will contribute to understanding neurodegenerative disorders like Alzheimer’s and Parkinson’s disease, multi-infarct dementia, frontotemporal dementia, amyotrophic lateral sclerosis and trinucleotide repeat disorders, in which a deterioration of neurovascular physiology involving alterations in tissue homeostasis contributes to motor and cognitive decline.
The expertise of our team, which includes neuroscientists, clinicians, physicists, engineers and computational scientists, extends beyond the boundaries of traditional biological and clinical sciences. Accordingly, the innovation falls into multiple categories:
- Development of new technologies for imaging and intervention in animal models of human disease.
- Integration of these imaging technologies with novel genetic tools for measurement of vascular and metabolic activity following controlled manipulation of neuronal circuits.
- Application of new imaging tools to basic biological questions of neurovascular physiology in healthy brains and neurovascular pathology in neurological disease and stroke.
- Development of computational frameworks directly applicable to clinical studies.
Imaging studies in animal models of human disease is necessary to establish a defined set of functional markers characterizing the progression of neuropathology. The outcome measures guide the development of novel therapeutic, preventive and diagnostic approaches.
UC San Diego's Neurosciences Department is uniquely positioned to train a new generation of young scientists and clinicians as it combines world-class experts in basic and clinical neuroscience and has a stellar track record in research on neurodegenerative disease. The Neurovascular Special Interest Group is a broad trans-disciplinary collaboration bringing together the necessary expertise and creating a framework for training new generation of scientists capable of interacting across traditional boundaries.