Resources at PENN
Institutional Training Grants
PENN has several institutional training grants that are especially useful to the mission of the CENT. Three important ones are:
Research Training in Neurologic Rehabilitation (T32 HD07425; Richard Salcido, MD, PI). This NIH/NICHD-supported program supports 6 fellows at a time and promotes postdoctoral research training in a broad range of skills relevant to rehabilitation of persons with neurological disabilities, from the molecular biology of neural regeneration to the cell biology of pressure sore wound healing to the design of rehabilitation outcomes measures. Established in 1992 with Dr. Selzer as PI, the program is now under the leadership of Dr. Richard Salcido, Chair of the Department of PM&R. This highly successful collaboration between PENN and the MossRehab hospital, with Dr. John Whyte serving as co-PI for MossRehab and Dr. Michael Selzer as co-PI for PENN, brings together over 30 faculty from PENN and MossRehab, and has trained MDs and PhDs, physiatrists and neurologists, physical therapists and bioengineers. Most trainees have gone on to academic positions and are active in research.
Brain Injury Training Grant (T32 NS043126; M. Sean Grady, MD, PI). This program marshals the research expertise of 24 faculty members University-wide to train 4 postdoctoral fellows at a time in the neuroscience of traumatic brain injury, aimed at protecting the brain from secondary neuronal damage and promoting recovery of structure and function. The program also provides short term research experiences for two medical students. This training grant, and its faculty, apply basic science skills to one of the major classes of disorders leading to long term disability in the US and around the world.
Research Cores and Centers
The Penn Center for Brain Injury and Repair (previously called the Head Injury Center), Douglas H. Smith, MD, Director, has been in existence for more than 30 years and is one of only five designated Brain Injury Centers nationwide, an honor bestowed by the National Institutes of Health. More than 20 principal investigators and their research personnel form the Center for Brain Injury and Repair. They represent a diversity of disciplines that span Neurosurgery, Bioengineering, Pharmacology, Pathology, Neurology, Pediatrics, Neuroradiology, Rehabilitation and Emergency Medicine. This team comprises one of the strongest, most integrated research teams in the world. Working in a highly collaborative environment, these researchers are studying ways to significantly improve the quality of life for people suffering from traumatic brain injury (TBI) and to prevent the "secondary" or delayed injuries that are initiated by brain trauma. Work from the Center has been documented in over 300 peer-reviewed articles published in international scientific and medical journals. We have made significant progress in understanding brain trauma over the past three decades. For example, we now know that cell damage and death might continue for many weeks and even years after TBI. Thus, the potential recovery period for patients with TBI and opportunity for therapeutic intervention is much longer than previously believed. Other accomplishments include:
Discovery of the mechanisms causing diffuse axonal injury (diffuse damage to nerve fibers), the most important and debilitating aspect of traumatic brain injury.
Discovery that damage to axons in the white matter is the source of post-traumatic coma.
Discovery of an anatomical link between traumatic brain injury and the development of post-traumatic epileptic seizures.
The first experimental evidence linking traumatic brain injury with Alzheimer's, Parkinson's and other neurodegenerative diseases.
Extensive pre-clinical and clinical evaluation of potential therapies for traumatic brain injury.
The development of novel MRI imaging techniques to better diagnose forms of traumatic brain injury.
A greater understanding of the importance of monitoring the increased pressure on the brain that commonly occurs after injury. This greater understanding led to the development of a device to measure cranial pressure that is now a key component of the management of brain injury.
Discovery of several mechanisms of secondary injury after brain trauma, leading the way towards developing new therapies.
Penn Program for Neuroprotection (Marc A. Dichter, MD, PhD, Director). This university-wide program is focused on translational research in neuroprotection. Many candidate pathways and drugs are being developed in the laboratory, both at PENN and at outside institutions, especially pharmaceutical companies, that are directed at protecting the nervous system from acute or chronic injuries. Despite a large, and increasingly active, effort, no successful strategies have emerged to effectively treat stroke, head trauma, status epilepticus, Alzheimerís disease, Parkinsonís disease, amyotrophic lateral sclerosis, etc. One major obstacle in this effort is the translation of exciting laboratory findings into clinical trials. The Penn Program in Neuroprotection brings together clinical investigators in many areas of both adult and pediatric neurological diseases to facilitate the development of early proof of principle trials that can be used to demonstrate whether promising candidate drugs are likely to work in man.
Center for Dynamic Imaging of Nervous System Function (Two-Photon). Two-photon microscopy will form a vital component of CENT because of its potential for viewing neuronal structures in living tissue, particularly in small animals, such as mice and rats. Fluorescently labeled images up to 150 μm, and in some circumstances 450 μm, below the tissue surface can be viewed on line or reconstructed by computer. Thus for example, neural progenitors injected into a mouse spinal cord can be viewed subsequently by exposing the cord in the anesthetized animal and viewing it with the two-photon microscope. The live transplanted cells could also be viewed in isolated slice preparations. The Center for Dynamic Imaging of Nervous System Function is directed by Dr. Haydon, a member of the CENT Executive Committee, and was founded in 2003 with funds from the National Institutes Of Neurological Disorders and Stroke (NINDS) National Institutes of Health (NIH) with matching support from The Children's Hospital of Philadelphia (CHOP) and The University of Pennsylvania (PENN) School of Medicine, the Departments of Neurology and Neuroscience, and generous support from EXFO Burleigh and Olympus Microscopes. This Dynamic Imaging Center has already catalyzed new studies and augment existing studies in the 21 qualifying NIH-funded laboratories that comprise it. The resultant synergistic interactions between faculty members are revolutionizing our ability to study basic functions of nervous system function and will ultimately enhance our understanding of these functions in human health and disease.
Confocal Laser Imaging Core. The Confocal Imaging Core is administered by Dr. Balice-Gordon, a member of the CENT Executive Committee. By comparison with two-photon microscopy, confocal laser microscopy provides higher resolution but can detect signals to a depth of only approximately 75-150 μm below the surface. Thus it can be used to image neuron processes in tissue slices, in small isolated CNS preparations such as the lamprey spinal cord, and on the surfaces of exposed tissues such as neuromuscular junctions.
Small Animal Imaging Program of the University of Pennsylvania
The small animal imaging program at Penn provides state of the art imaging capabilities to participating investigators in a variety of disciplines -- NMR, Optical Imaging, Positron Emission Tomography (PET), Single Photon Emission Computerized Tomography (SPECT), Computer Tomography (CT) and Ultrasound. The program consists of a core of imaging facilities, ancillary cores and world-class research programs. With the assistance of Dr. Stephen Pickup, the Director of the Small Animal Research Core, as well as through collaboration with imaging experts in the various ancillary cores and research programs, will be able to utilize the full capabilities of the University of Pennsylvania Small Animal Imaging Program. The PET, SPECT and CT components of the this core facility comprise an NIH-funded Small Animal Imaging Center, the PI of which is Dr. R. Nick Bryan, Chairman of the Department of Radiology and a member of the CENT Executive Committee.
University of Pennsylvania Molecular Imaging facility. A, A-PET small animal PET scanner. B, Combined F-18/FDG scan of a rat, with the F-18 revealing bone uptake, while the FDG accumulates in a tumor implanted on the shoulder (arrow). C, Imaging a mouse with Prism 3000XP SPECT camera. D, SPECT scan of tumor in a mouse brain. E, ImTek micro-CT scanner.