A mouse model of graded contusive spinal cord injury.

A mouse model of spinal cord injury (SCI) could further increase our basic understanding of the mechanisms involved in injury and recovery by taking advantage of naturally-occurring and genetically engineered mutations available in mice. We have, therefore, investigated whether methods used to produce and evaluate graded experimental contusive SCI in the rat could be modified to produce a mouse model of traumatic SCI. C57BL6 mice were anesthetized with 2,2,2-tribromoethanol and a restricted laminectomy performed at the T8 vertebral level. The spinal column was stabilized and a weight drop technique used to produce contusive injury. Experimental groups were distinguished by the amount of weight or the height from which the weight was dropped onto an impounder resting on the dura (1 g x 2.5 cm, 2 g x 2.5 cm, 3 g x 2.5 cm, and 3 g x 5.0 cm). Functional deficits over time were examined up to 28 days after SCI by testing hindlimb reflex responses and coordinated motor function. Chronic lesion histopathology was evaluated by light microscopy and analyzed with morphometric techniques. All groups demonstrated profound functional deficits after injury followed by gradual recovery. Recovery correlated with the weight dropped and percent of white matter spared that was 41.3+/-6.0% (mean +/- SEM) in the 2 g x 2.5 cm group and 24.3+/-5.0% in the 3 g x 2.5 cm group. A replicate experiment confirmed reproducibility of the injury. This new mouse model of contusive SCI could pave the way for in vivo studies of the effect of genetic modifications produced by specific mutations on injury and recovery processes after spinal cord trauma.

Neurotrophic factors increase axonal growth after spinal cord injury and transplantation in the adult rat.

The capacity of CNS neurons for axonal regrowth after injury decreases as the age of the animal at time of injury increases. After spinal cord lesions at birth, there is extensive regenerative growth into and beyond a transplant of fetal spinal cord tissue placed at the injury site. After injury in the adult, however, although host corticospinal and brainstem-spinal axons project into the transplant, their distribution is restricted to within 200 micron of the host/transplant border. The aim of this study was to determine if the administration of neurotrophic factors could increase the capacity of mature CNS neurons for regrowth after injury. Spinal cord hemisection lesions were made at cervical or thoracic levels in adult rats. Transplants of E14 fetal spinal cord tissue were placed into the lesion site. The following neurotrophic factors were administered at the site of injury and transplantation: brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), ciliary-derived neurotrophic factor (CNTF), or vehicle alone. After 1-2 months survival, neuroanatomical tracing and immunocytochemical methods were used to examine the growth of host axons within the transplants. The neurotrophin administration led to increases in the extent of serotonergic, noradrenergic, and corticospinal axonal ingrowth within the transplants. The influence of the administration of the neurotrophins on the growth of injured CNS axons was not a generalized effect of growth factors per se, since the administration of CNTF had no effect on the growth of any of the descending CNS axons tested. These results indicate that in addition to influencing the survival of developing CNS and PNS neurons, neurotrophic factors are able to exert a neurotropic influence on injured mature CNS neurons by increasing their axonal growth within a transplant.

Motor function analysis of myelin mutant mice using a rotarod.

We have examined motor control in normal and shiverer mutant mice using the rotarod assay, a forced motor activity which tests for balance and co-ordination. Shiverer mice carry a deletion of the myelin basic protein (MBP) gene, resulting in CNS dysmyelination and characteristic motor dysfunction. Homozygous mutant mice had a significant increase in cumulative falls from the rotarod relative to heterozygous mice. Non-acclimated animals of both genotypes showed progressive improvement in performance when tested on successive days. The rotarod test also discriminated shiverer mutants from animals that received gene therapy intervention. Shiverer animals carrying an MBP transgene showed gene-dosage-dependent improvements in motor function, and mutants which received thalamic transplants of wild type oligodendrocyte precursor cells showed improvement relative to sham operated and non-transplanted controls. Thus the rotarod is a sensitive measure of motor function in hypomyelinated mice, and may be useful for assessing the results of experimental manipulations including transgenic gene therapy and cell transplantation.

The relationship between the ingestion of hot coffee and intraoesophageal temperature.

Temperatures at the lower end of the oesophagus were taken during the ingestion of hot coffee at varying temperatures and varying volume, by using a modified duodenal tube. TEMPERATURES HIGHER THAN EXPECTED WERE FOUND: of 209 measurements on 17 patients and one volunteer, standardized for size of sip and temperature of coffee, 43% were 44 degrees C or higher (up to 53 degrees C). Statistical analysis showed a linear relationship between the intraoesophageal and the initial coffee temperatures.Volume has a larger effect than the temperature at which the coffee is taken.The average increase in intraoesophageal temperatures at the point of measurement was 0.381 degrees C per ml coffee ingested. Some implications of the findings are discussed from the epidemiological point of view.