Center for Neurotrauma Research (CNTR)
The Medical College of Wisconsin recently launched the Center for Neurotrauma Research (CNTR) with the Department of Neurosurgery. The CNTR’s multidimensional mission is to advance the science of neurological trauma and related diseases, enhance the translation of brain and spinal trauma research into clinical care innovations, foster the professional development of future scientists, and improve the health of communities throughout the region and state. Within MCW, the CNTR functions as a collaborative hub for neurotrauma research and will create a synergistic collaboration with other MCW Centers such as the Comprehensive Injury Center, Neuroscience Research Center and the Center for Imaging Research.
The CNTR builds upon the successful track record of the neurotrauma research program in the Department of Neurosurgery spanning more than 25 years, including dramatic growth over the past 10 years. The creation of the CNTR reflects MCW’s scientific progress in this field and the program’s current standing in the international neurotrauma research community. The CNTR is co-directed by Shekar Kurpad, MD, PhD, Sanford J. Larson Professor and Chair of Neurosurgery; and Michael McCrea, PhD, Professor of Neurosurgery, Eminent Scholar, Vice Chair of Research and Director of Brain Injury Research.
Other Labs & Research Facilities
The Biomechanics Laboratories include an overhead swinging pendulum laboratory capable of speeds up to 12 m/s with mini-sled apparatus on linear precision bearings with 3-m run-out. Materials testing laboratory has one electrohydraulic piston apparatus with a 25 cm stroke and dynamic capabilities, and a second piston with dual motion (rotation and vertical) capabilities for smaller construct evaluations. Six high-intensity lights (4 kW each). Data Acquisition System (TDAS, Diversified Technical Systems, Seal Beach, CA), 128 channels at 12.5 kz/channel sample rate. Both data acquisition systems have pre-amplifiers and antialiasing filters. Vicon motion analysis system with nine high resolution cameras (Vicon Corp., Oxford Metrice, Oxford, England), capable of measuring sub-millimeter motions and angulations. Five Phantom (Vision Research Inc., Wayne, NJ) digital video cameras capable of imaging at 1,000 to 10,000 frames/second. Kodak high-speed video camera system capable of up to 4,500 full frames/second and a high-speed, high-resolution digital video camera capable of 1,000 frames/second data acquisition. Motion Analysis Corp., four-camera, 3-D high-resolution motion tracking system. Hybrid III ATD with force and acceleration transducers. Force, displacement, and acceleration transducers, Kistler 3-axis force plate, Denton 6-axis force transducers, 3-axis motion transducer, Endevco and Entran accelerometers. Heavy-duty cryomicrotome device with electronic control (Leica Inc., Deerfield, IL).
Portable x-ray machine and C-arm x-ray. Pure-moment testing rig capable of applying pure moments to spinal motion segments, cervical spines, or intact head-neck complexes, measuring six axis forces and moments, and three-dimensional kinematics. Vicon motion analysis system with six high resolution cameras (Vicon Corp., Oxford Metrice, Oxford, England), capable of measuring sub-millimeter motions and angulations.
The Histology Laboratory is fully equipped and staffed, capable of all routine techniques, including silver stains, Trichrome stains, paraffin sectioning and cryostat sectioning.
- Leica LaborLux D microscope
- Cryostat for autoradiography and routine frozen sectioning, rotary microtome, sliding microtome, Autotechnicon tissue embedder, and Buehler diamond saw
- Nicolet evoked potential monitoring system
- NYU spinal cord injury impactor device. Two Forma water-jacketed incubators
- Two isolated SterilGARD hoods (Baker Co. Inc.)
- Thermo IEC Centra-CLR3 centrifuge
- High-resolution Nikon dissecting microscope, fiber optic light illuminator source
- Nikon TE2000 inverted microscope with epi- and fluorescent illumination
- Nikon E600 upright microscope with epi- and fluorescent illumination, Spot II digital camera system, imaging monitor, and MetaMorph image analysis software
- Dedicated refrigerator and freezer for storing culture media supplies
- NYU spinal cord injury impactor device
- Surgical microscope, (Moller Wedel Inc.)
- Dell Dimension workstation computer system
- BioRad I-cycler real-time thermocycler
- Denver balance, microwave
- Fisher microcentrifuge
- pH meter
- BioRad semi-dry gel transfer apparatus
- BioRad mini-protein gel electrophoresis tanks with power supplies
- Owl DNA/RNA electrophoresis tanks
- Harvard Apparatus blood pressure-monitoring machine
- Harvard Apparatus pulse oximeter
- American Optical 2-headed teaching microscope
- Designated refrigerator/freezer
- Nanopure Infinity water system
- Ultraviolet gel-viewing table
- Eppendorf refrigerated microcentrifuge
- Hot plates, stirrers, platform shaker, vortexers, glassware, plasticware, incubator oven and water bath
- Vicon nine-camera, high-speed motion capture system and software for 3D motion analysis
The Neurosurgery Research Facility (NRF) consists of a Seattle Safety designed horizontal acceleration impact sled. The sled has a nominal force of 1.4MN, with a 2000 mm stroke, maximum velocity of 75 kph, and peak acceleration of 80 Gs. The sled is computer controlled from the control room adjacent to the test pad. The input pulse is entered in digital format. Individual crash pulses can be programmed to a high degree of accuracy. The system “learns” from prior tests with the same programmed input, and fine tunes the firing and breaking pressure for the next test. This allows for a greater accuracy in delta-V, acceleration, and pulse width. Prior to firing, a servo-brake holds the sled in position while the pneumatic actuator is charged. With the input pulse loaded, and the actuator fill valves filled, the sled can then be fired. If an abort situation is needed, a “cancel” button in the software, and an emergency stop button on the charge enable box will immediately bleed the firing pressure, disarm the system, and abort the test. The NRF’s test track is also leveled with laser precision, high-intensity lights are used for lighting, and heating/air-conditioning controls the temperature and humidity. Around the sled, there is adequate space for placement of high-speed digital video cameras and a Vicon motion analysis system.
Computer Analysis and Data Server facilities consist of desktop and laptop PC and Macintosh computers throughout the labs. A dedicated and secure 4TB server that is serviced by the MCW IT department is housed in the laboratory that all authenticated users have access to. Storage locations for each project are secured with permissions that allow only registered users that are included on approved project protocols. Data is backed up nightly with long-term data storage off-site. Software includes MatLab computational package with tool boxes, STATA statistical package, ABAQUS (6.3 standard and explicit), Motion Analysis Package Motion Analysis Corp. 2-D system and 3-D software, and ImageExpress.
SCI is a relatively frequent event; estimates suggest that 12,500 new cases of SCI occur every year in the US alone. In the US, approximately 276,000 persons live with SCI, which has a huge impact on their lives and families, and has tremendous socioeconomic and medical costs. The main causes for SCI are motor vehicle accidents (38%), falls (30%), acts of violence (14%) and sports injuries (9%) (National SCI Database).
The type and degree of disability that is caused by SCI is determined by the location and extent of the injury. Spinal cord tissue is damaged in the injury process and this damage is occurring in two steps. The initial damage, the primary injury, is caused by the mechanical trauma to the spinal cord during the accident.
This is followed by the secondary injury, which is caused by a number of events including hemorrhage and inflammation. While acute inflammation is observed in all tissues as a response to injury and is an important prerequisite for the healing process, prolonged and unresolved inflammation, as it is present after SCI, strongly contribute to the tissue damage. Immune cells in the tissue produce factors that maintain and stimulate the inflammatory response and produce factors that contribute to tissue damage.
Red blood cells (RBCs), which are present in the spinal cord tissue due to the hemorrhage, are taken up by phagocytic cells like macrophages. This can result in increased production of pro-inflammatory cytokines and chemokines, factors that activate immune cells. Previous experiments have shown the relevance of some of these factors after SCI. For example, the absence of one of these cytokines, TNF, leads to a better recovery in mice after SCI and reduces inflammatory activation of cells at the injury site. However, these extent of these results suggests that other factors also contribute to the tissue damage.
We are now attempting to investigate further mechanisms contributing to the secondary tissue damage, including other cytokines and chemokines which may play a role after SCI. We aim to modulate these and investigate the effect on recovery after SCI.
Ultimately, our goal is a translational treatment approach to reduce secondary damage after injury and to improve the outcome and quality of life after SCI.
In summary, the broad goal of my research is to investigate and modulate the inflammatory tissue response after spinal cord injury (SCI) with the aim to reduce the secondary damage and thereby to improve the functional outcome after SCI.