Overview

The Department of Neurosciences is chaired by Bruce D. Trapp, PhD and comprises a core of internationally recognized basic, translational and clinical scientists. The Department is divided into several core groups or “Centers” that focus on fundamental aspects of brain function and the pathogenesis of human diseases. Departmental researchers directly investigate the pathogenesis of human central nervous system (CNS) diseases at all levels of analysis. This ranges from strong basic science programs which have resulted in the development of multiple animal models of human neurological and neurodegenerative diseases to the development of a unique rapid autopsy program for the study of multiple sclerosis (MS). The overall goals of the Department are to elucidate the causes of nervous system diseases and to develop therapeutics that stop or delay their progression. The interactions between Staff in the Departments of Neurosciences, Neurology, Neurological Surgery, Radiology and Behavioral Medicine provide a unique environment for reaching these goals.

Nervous System Development, Plasticity and Repair

A major strength of the Department is developmental neurobiology research. Interests range from stem/progenitor cells to the function of disease-related genes including the amyloid precursor protein (APP), chemokines, myelin proteins, neurotransmitter receptors, BACE1 and the reticulins. The Department is noted internationally for its program in glial development. Dr. Trapp has recently discovered a primitive neural cell with stem-cell-like characteristics. These cells show a remarkable capacity to generate new myelin in a rodent model of human myelin disease. Richard Ransohoff, MD recently identified a role for chemokines in oligodendrocyte colonization of the developing rodent brain. Hitoshi Komuro, PhD is internationally known for his work on cerebellar development, especially migration of granule cells. Sanjay Pimplikar, PhD uses both rodent and zebrafish models to study the function of APP during development. Riqiang Yan, PhD investigates the role of BACE1 in myelination. Several recent Staff additions have greatly strengthened research in neuronal plasticity and repair. James Kaltenbach, PhD investigates neuronal plasticity as a basis of central auditory disorders including tinnitus and hyperacusis. Ching-Yi Lin, PhD investigates cellular and molecular mechanisms of neuronal plasticity of the CNS. Yu-Shang Lee, PhD studies the mechanisms and potential treatment of spinal cord injury, with special emphasis on neurorehabilitation and nerve regeneration strategies. Jianguo Cheng, MD, PhD studies motor control and the mechanisms and treatment of pain. Finally, our newset Staff addition, Selva Baltan, MD, PhD focuses on mechanisms of brain cell damage and axonal injury following stroke in a region-specific and age-specific manner.

Multiple Sclerosis Research

The glial research program has close ties with physicians in Cleveland Clinic’s Mellen Center for Multiple Sclerosis Treatment and Research, which houses one of the largest clinical MS programs in the world. Dr. Trapp’s studies on the function of myelin proteins in mice demonstrated that long-term axonal survival depends upon trophic support from myelin. As an extension of these basic science studies, he and colleagues described axonal degeneration as a major cause of neurological disability in MS patients. In collaboration with Susan Staugaitis, MD, PhD, Departments of Neurosciences and Anatomic Pathology, Richard Rudick, MD, Director of the Mellen Center, and Beth Fisher, PhD, Biomedical Engineering, Dr. Trapp developed a rapid autopsy program for individuals with MS. Dr. Staugaitis attends these autopsies and participates in interpretation of research histology. A unique aspect of these autopsies is a postmortem MRI that has been instrumental in defining pathological correlates of MRI abnormalities. Dr. Rudick also directs clinical trials in MS and is interested in outcome measures and surrogate markers for disease progression in MS patients. The MS group is supported by an NIH Program Project Grant (PPG) directed by Dr. Trapp.

Neurodegenerative Diseases

The growing neurodegenerative disease research program includes Riqiang Yan, PhD, Bruce Lamb, PhD, Sanjay Pimplikar, PhD, and Stephen Rao, PhD. Dr. Yan investigates molecular mechanisms of neurodegeneration in Alzheimer’s disease (AD), focusing on the role of β-secretase, its interacting proteins and modification of its activity in disease pathogenesis. Dr. Lamb’s research focuses on the genetic, therapeutic and environmental factors modifying AD pathogenesis using transgenic mouse models of the disease. Dr. Pimplikar examines the normal biological functions of APP in both zebrafish and the mouse and the implications for neurodegenerative disease mechanisms underlying AD. Finally, Dr. Rao has joint appointments in the Departments of Neurology and Neurosciences and is Director of the Schey Center for Cognitive Neuroimaging. Dr. Rao examines the functional neuroimaging correlates of neurodegenerative disease pathogenesis, with interests in AD, Parkinson’s disease (PD) and MS. The program is integrated through journal clubs, fellows’ seminars, and monthly neurodegenerative disease meetings as well as current ongoing plans for a program project grant.

Parkinson's Disease and Movement Disorders

This research group focuses on the functional and physical changes in patients with movement disorders, the mechanisms of deep brain stimulation (DBS), and the development of new applications for DBS. Research incorporates investigators from the Institute’s Departments of Neurosciences and Biomedical Engineering as well as faculty from the Departments of Neurology, Neurological Surgery and Radiology. This group is unique in that it uses a multidisciplinary approach to understanding how neurological diseases arise and progress within the CNS and then works to translate these understandings into clinical therapeutic applications. Andre Machado, MD, PhD, is the Director of the Center for neurological Restoration and he investigates the use of cerebellar stimulation to induce recovery of motor skills following stroke. Dawn Taylor, PhD, works on closed-loop systems for DBS programming and the use of chronic recording from cortical neurons to develop prosthetic devices. John Gale, PhD, investigates pathophysiology of the basal ganglia and the use of deep brain stimulation in the treatment of neurological disorders. Cameron McIntyre, PhD, Biomedical Engineering, models the effect of stimulation on neuronal tissue using finite element models of neural tissue based on anatomical and electrophysiological data from primates with Parkinsonism. Jay Alberts, PhD, Biomedical Engineering, uses quantitative kinematic measures to assess the effects of DBS on motor control and daily living experiences of PD patients, including the interaction between cognitive and motor function and the effect of exercise on PD motor symptoms. Micheal Phillips, MD and Mark Lowe, PhD from the Department of Radiology are also members of the NMRC and study the mechanisms of DBS using functional MRI to evaluate the network changes that take place during DBS in PD patients. Scott Cooper, MD, PhD from the Center for Neurological Restoration studies mechanisms of DBS through imaging, modeling and quantitative kinematic studies in dystonia and PD. Debabrata Ghosh, M.B.B.S, from the Department of Neurology rounds out the investigative team, focusing on mechanisms of DBS.

Neuroinflammation Research Center (NIRC)

Dr. Ransohoff directs the NIRC, which includes four investigators. NIRC scientists conduct multidisciplinary translational research to address neuroinflammation in human disorders including MS, AD, PD, ALS and stroke. Our internationally recognized initiative in MS incorporates Staff from Neurology, Radiology, Immunology and Biomedical Engineering, provides a template for program development and exemplifies bench-to-bedside evolution. Our current foci include neuroimmunology, leukocyte trafficking, blood-brain barrier function, cytokine action and signaling, and innate immune mechanisms (including Toll-like receptors) in furtherance of the mission to understand how the CNS interacts with the hematogenous compartment and the peripheral nervous system. Stephen Stohlman, PhD and Cornelia Bergmann, PhD have established a program of study in viral models of MS. Dr. Bergmann has obtained a PPG to investigate the regulation and function of T cells during viral infections of the CNS associated with demyelination. Dr. Stohlman investigates mechanisms of immune induction, access of CNS immune effectors, and the basis for cell-type-specific antiviral immunity in models of CNS inflammation associated with demyelination. J. Javier Provencio, MD, Cerebrovascular Center with a joint appointment in the NIRC, has developed a new mouse model of cerebral vasospasm to study how inflammatory cells in the cerebrospinal fluid precipitate ischemic stroke in patients who have suffered subarachnoid bleeding.