Luis de Medinaceli

An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks

Abstract There is no widely accepted quantitative method for evaluating the functional effects of peripheral nerve damage in animals. In the present study, a method for evaluating sciatic nerve damage was developed from measurements of the prints of the hind feet of walking rats preserved on X-ray film. Four variables were measured from these tracks, and comparisons between the damaged (experimental) and intact (normal) side were converted to percent deficits and averaged to obtain a “sciatic functional index” (SFI). The SFI was then measured under normal conditions, after nerve transection, nerve crush, and sham procedures. Reliability and repeatability of the SFI were found to be excellent. The effects of sciatic nerve transection and nerve crush evaluated by this method agreed very well with other methods of evaluating nerve damage. We conclude that the SFI provides a simple, accurate, reliable, and repeatable method for evaluating the functional condition of sciatic nerve in rats.

Rat sciatic functional index data management system with digitized input

Quantification of the functional condition of rat sciatic nerve is an important experimental procedure. In the present study, a system for management of the sciatic functional index ( SFI ) data is described. Results obtained with the Sciatic Index Management System (SIMS) were compared with results obtained with other measurement techniques. Validity and reliability of the SIMS were found to be excellent, and speed of data analysis was increased. It is concluded that the SIMS represents a significant advance in the quantification of nerve regeneration data.

Peripheral nerve reconnection: Improvement of long-term functional effects under simulated clinical conditions in the rat

Despite increasing precision of the microsurgical management of peripheral nerve injuries, measured by eventual return of function, there has been no clear improvement in the outcome. By taking into consideration a number of chemical and physical factors that could influence the condition of injured nerves, we developed a reconnection technique and have applied that technique under conditions mimicking those of human nerve injury. Within 4 weeks, all rats treated by reconnection had substantial return of motor function as measured by gait. Seventy-four days after surgery, performance of the animals receiving this reconnection treatment was 66% better than that of the animals treated by conventional microsuturing.

Peripheral nerve reconnection: Inhibition of early degenerative processes through the use of a novel fluid medium

Two pharmacologic manipulations were applied to injured nerves in the rat to minimize the secondary damage that accompanies peripheral nerve transection. It is known that calcium influx into the nerve is responsible for some of the processes that have been termed Wallerian degeneration. These disruptive effects of high intracellular calcium were retarded by chlorpromazine, a potent inhibitor of calmodulin. Our results suggested a new method for reducing posttraumatic neural disruption and supported our hypothesis regarding the involvement of calmodulin or some other Ca2+ binding protein in Wallerian degeneration. The second part of this report describes changes observed at the tips of a severed nerve and their prevention through the use of polyvinyl alcohol. Finally, we showed that neither substance produced functional deficits when injected directly into the sciatic nerve of rats and could thus be used in animal experimentation.

Functional consequences of experimental nerve lesions: Effects of reinnervation blend

In spite of a constant and irrepressible growth of sprouts from the proximal stump of peripheral nerves that have been injured, functional recovery varies greatly from one case to another. To try and understand the reasons for this variability, I have proposed a novel view of the events occurring in a regenerating nerve; based on this view, a probability model was designed that could represent all situations observed after nerve injury. This model, described elsewhere, is based on the assumptions that the guidance role of basal lamina tubes is fundamentally important and that when this guidance fails, regrowth is random. In the present study, this model was tested; behavioral results were measured after various procedures on rat sciatic nerve, and these data were compared with results predicted for similar injuries through the probability model. A good correlation was observed between theoretical and experimental results, indicating that the probability model was reliable. Using this model as the basis for my conclusions, the inconsistent results of current surgical techniques of nerve repair were tentatively explained.

Functional consequences of experimental nerve lesions: Effects of time, location, and extent of damage

The purpose of this experiment was to investigate the part played by each of the four fundamental components of a nerve in functional recovery from injury. In order to single out the role of cellular elements (the neurites), tissular elements (the Schwann cells), structural elements (the basal lamina tubes), and the blood-nerve barrier, various crush lesions were made on sciatic nerves of rats and functional recovery was studied. I examined the effects of the location and number of damaged sites and of the time elapsed between successive injuries. Results were assessed for a post-operative period of 2.5 months by studying tracks obtained from walking rats. This study suggested that (a) as far as neurites were concerned, the location of injury influenced the recovery pattern but the extent of damage did not; (b) the extent of damage to the Schwann cells had no measurable influence; (c) long-lasting deficits could be attributed to disruption of the basal lamina tubes, and (d) damage of the blood-nerve barrier could be responsible for slight and temporary disruption of the recovery pattern. I did not observe any of the possible beneficial effects of conditioning lesions described by some authors. This study emphasized the role of the basal lamina tubes in nerve injury and regeneration.

Is vigor of regeneration a key factor in recovery from peripheral nerve injuries

The nerve-growth-promoting effects of the tricyclic antidepressant, imipramine, were tested on the sympathetic ganglion of chickens and on the sciatic nerve of rats. A powerful neuronotrophic action was observed in vitro, but the utilization of the drug in vivo did not modify the functional recovery from a crush lesion.

An anatomical landmark for procedures on rat thoracic spinal cord

A vein is described that allows easy identification of the fifth thoracic vertebra of the rat. Leading from the dorsal hibernating gland to the azygos vein, the vessel was present in each of 135 rats.

Posttraumatic autoimmune reaction in peripheral nerve: Effect of a single injury

This study was conducted to show that local autoimmune reactions could be observed in rat sciatic nerve after a single injury. Furthermore, we attempted to correlate the intensity of the immunological reaction with the severity of nerve damage, with the type of surgical treatment and with the degree of functional recovery. Through the use of direct immunofluorescence techniques, we found that the severity of the initial damage was associated with the intensity of the local immunological response assessed 2.5 months after surgery. There was an association between type of surgical treatment and intensity of the autoimmune reaction. A correlation between autoimmune reaction and degree of long-term functional impairment was not immediately clear. The probable factors that underlie these results are discussed.

A method for shortening of the rat spine and its neurologic consequences.

Large laboratory animals are the usual choice for complex surgical procedures on the spine and spinal cord, such as shortening of the spine. It would, however, be advantageous to be able to use a small inexpensive mammal like the rat. We describe a procedure which allows thoracic spondylectomy (T8-T9) to be performed in the rat with a satisfactory survival rate (69%). Functional consequences of the procedure on animals with uninjured spinal cord were monitored over a period of six months, at which time histologic examination was performed. There was a good correlation between operative trauma, consisting of mechanical injury to the cord assessed from the surgical notes, and the duration of postoperative spinal shock. Animals for which the cord appeared laminated or deformed at the time of sacrifice tended to show incomplete functional recovery. Cord cavitation developed, in most surviving animals (78%) but did not have a measurable adverse effect on functional outcome. In the present study, the cord was not intentionally injured; however, availability of this procedure may facilitate the future development of methods to implement recovery of function following spinal cord injury.