Five Cores have been developed over the last 20 years of funding of the Program Project Grant.
The Administrative Core ensures that the complex and interrelated experiments are carried out efficiently and the results communicated and published in a timely fashion. This is achieved through regularly scheduled and highly interactive meetings of the members of the Spinal Cord Center, regular assessment of progress, coordination of consultant and travel activities, and centralized record keeping.
All Projects use behavioral methods to assess the functional significance of the interventions. The Behavior and Biomechanics Core provides a central facility for routine training and testing of animals and designs an appropriate battery of functional assessments for each spinal injury model. A web-based archive of training videos and behavioral protocols has been developed and is maintained. Experienced personnel ensure the standardized testing and analysis required to provide the most reproducible results and to facilitate the comparison of the effects of different treatments. Evaluation of the efficacy of biologically active interventions after spinal injury is the major concern of this Core. Test selection continues to be the subject of considerable debate. Several factors influence these choices such as:
1) Rapid acquisition of data.
2) Test reliability.
3) Test sensitivity.
4) Individual investigator preference.
An ideal test should be rapid, reliable, and sensitive to the location and extent of the injury, the degree to which the intervention improves the integrity of the injured region, and the degree to which intervention affects plasticity beneficially. Because restoration of function is usually incomplete, the tests should assess not only the degree of damage to the intended structure but also residual impairment. A number of convenient sensorimotor tests have been developed that are not altered by repeated testing, do not require training, aversive motivation or food deprivation, and appear to be very useful in established models of spinal cord injury. Food and water deprivation procedures or aversive motivation are required for some tests, but these manipulations may have profound effects on functional outcome.
Usually, it is necessary to test a range of behaviors in each animal, since there will be an evaluation of animals receiving lesions of different sizes and locations, and transplants with different characteristics. Ideally a test will use quantitative methods that can provide some insight into physiological mechanisms and that are reproducible in other laboratories. The majority of these tests requires little or no training of the animals and thus can be administered efficiently. In addition, personnel in this Core will contribute to the development of new tests to evaluate deficits and recovery in bladder and respiratory function. Animals tested by the Core personnel are always coded through the database so that the individuals who test and evaluate the animals are unaware of their group assignment.
The complexity of the Projects in terms of using genetically modified cells for transplantation and delivery of therapeutic genes requires a central facility with technical expertise, equipment and ongoing training. Individual projects will use genetically modified fibroblasts and neural stem cells for the delivery of genes, including neurotrophins, to a spinal cord injury site. The facility also provides access to equipment for molecular analysis and assists with experiment design and data analysis.
The goals of the molecular and cell biology core facility are:
- to provide the necessary cells for grafting experiments
- to centralize the maintenance of cell stocks and recombinant viruses
- to provide quality control
- to develop molecular strategies for genetic modifications using plasmids and recombinant viruses
- to standardize cell biological and molecular procedures
- to assist with molecular analysis
. to train technicians, students and fellows in tissue culture, molecular biology and basic virology
The Molecular and Cell Biology Core facility provides uniform populations of cells with minimal variations. Students and postdoctoral fellows are trained to work with cells and constructs and are encouraged to initiate new applications and pilot projects. Morphology and Image Analysis
The goals of the Morphology and Image Analysis Core are:
1) to manage tissue processing, sectioning and staining to insure standardization of morphometric techniques
2) to supervise and train members of the Spinal Cord Center in the proper methods of image acquisition and analysis.
The centralized maintenance of the Core facilities provides optimum working conditions for investigators and ensures that equipment remains in working order to serve the large number of users. The Core provides standardized techniques and equipment employed in animal perfusion, immunocytochemistry, tract tracing, cell counting, and digital image acquisition. The Core provides structured training for technicians, graduate students and postdoctoral fellows in many techniques including animal perfusion and dissection, tissue processing, immunocytochemistry, tract tracing and image acquisition and stereological analysis
The purpose of this Core is to assure uniformity of surgical procedures and postoperative care, to train staff, graduate students and postdoctoral fellows to perform these procedures and to administer postoperative care. This standardized training improves the correlation between surgical lesions and anatomical and physiological outcomes.
The Surgery Core is responsible for the day-to-day operations and maintenance of the program project rodent database. This web-based, secure data base enables centralized management of all rodent records from purchase through the end of experimentation and tissue processing. The Core also assures that all faculty, staff, graduate students and postdoctoral fellows obtain the species-specific and OSHA certifications required to work with experimental animals. It also functions as the interface with the University Lab Animal Research staff and the veterinarian on all animal procedure issues. The Core maintains a multi-user surgical suite with pre- and post-operative areas procures all necessary surgical supplies and coordinates the scheduling of procedures to be performed in the Core facility.