Animal models of peripheral nerve injury
Section snippets
Chronic nerve banding in the lower extremity
A series of studies by Mckinnon et al looked at peripheral nerve injury. In their 1986 article in Hand Clinics, they reviewed their experience with banding the rat sciatic nerve.1, 11 Interval diameter tubes of 0.6, 0.9, 1.1, and 1.5 mm were used in nerve conduction/electromyography (EMG) changes observed after chronic banding of sciatic nerves exposed with the mean diameter of 1.3 mm. In the bands that were “tight” (0.6 + 0.9 mm), Wallerian degeneration was noted at 1 month. These cuffs
Chronic nerve banding in the upper extremity
In 1985, Mckinnon et al described a primate model for chronic nerve compression by using the sciatic nerve banding technique with silastic tube at the carpal tunnel.5 Four animals underwent the experiment with 6 months of tube compression. Carpal tunnel release was evaluated with or without internal neurolysis and evaluation of mean fiber diameter and percentage of neural tissue per specimen. These studies provided an interesting window into the effects of particular types of physical
Double crush syndrome
Dellon et al also used the banding techniques to evaluate the “double crush syndrome,” in which injury to the nerve at one level potentiates injury to the nerve at a second level of the peripheral nerve. In these studies, the rat sciatic nerves was banded with a silastic band × 7 months and then a second band applied either proximally or distally; at 5 months after conversion to double banding, the animals were killed. Their conclusion was that two sites of injury cause more diminution in
Pneumatic balloon compression
Other approaches have been employed to evaluate compression and its effect on the peripheral nerve. The classic study is by Rydevick et al.6 This in vivo study of the rabbit tibial nerve employed a pneumatic mini-compression device. With this device, the rabbit tibial nerve was dissected out and observed under an operating microscope with variable pressures over various time points. They observed interference with venular blood flow around the rabbit tibial nerve at a pressure of 20 to 30 mm
Short-term effects of nerve compression with pressure cuffs
Persistent intraneural edema has been observed in animal models after short-term compression at low pressures by Rydevik et al.18 In one of these studies, the extraneural pressure around the sciatic nerve of rats was elevated to 4.0 kPa (30 mm of mercury) for periods of 2, 4, 6, and 8 hours by the use of miniature pressure cuffs.19 In sham controls, the cuff was applied and left in place for 2 to 8 hours but was not inflated. Endoneurial fluid pressure was measured with a micropipette at 1 hour
Short-term compression studies
The biological effects of a brief, controlled nerve compression were studied in the rat sciatic nerve with small, inflatable cuffs.22, 23 In 91 rats, pressures of either 0, 30, or 80 mm Hg were applied for 2 hours to the nerve, and then the cuff was removed and the incision closed. At regular intervals up to 28 days, the nerves were removed and examined for evidence of injury. Within 4 hours, endoneurial edema formed within all compressed nerves and persisted for the entire time of the study.
Long-term effects of nerve compression
The same model was used to study the long-term effects of only 2 hours of extraneural compression applied to the sciatic nerve of rats.22 A pressure of 10.7 kPa (80 mm of mercury) was applied to animals in one group, and the nerve was excised for histological analysis at intervals of 4 hours and 1, 2, 7, 10, 14, and 28 days. In another smaller group of animals, pressures of 1.3 and 4.0 kPa (10 and 30 mm of mercury) were applied, and the follow-up intervals were 5, 6, and 7 days. Contralateral
Other mechanical effects on nerve function
Another fascinating study was performed by Szabo and Sharkey. In this study, a rat tibial nerve was subjected to 20,000 cycles of pressure (20, 30, and 50 mm Hg). The effect on the nerve to the effect of a static pressure equal the mean value of the pressure waveforms. Thus, a cyclic type of loading of a nerve can in some ways resemble the effect of a static loading at a given pressure. Other effects of loading on a peripheral nerve have been studied in terms of the effect of tension.29 In
Chronic compression models
To create a more directly applicable animal model for carpal tunnel syndrome with limited surgical dissection and a pneumatic device technique, Diao et al32 developed a nerve compression model using the rabbit. Although the rabbit paw anatomy is not the same as the human wrist, the rabbit paw has a carpal tunnel that is bounded by a flexor retinaculum and carpal bones and contains four tendons and a median nerve (Fig. 1). An angioplasty balloon catheter was inserted into the rabbit carpal
Repetitive loading model
Additionally, some models of repetitive use causing mechanical stress on peripheral nerves have been described. Thirty Sprague-Dawley rats were trained to pull on a bar with 60% maximum force 4 times per minute, 2 hours per day, 3 days per week, for 12 weeks. Model behavior and limb withdrawal threshold force were characterized weekly. Median nerves were harvested after 12 weeks and examined with immunohistochemistry for ED1-positive macrophages, collagen, and connective tissue growth factors.
Crush injuries, lacerations and effects of other physical modalities
Nerve crush has been performed in animal peripheral nerves, and the effect both on pain, motor function, and other aspects of peripheral nerve function has been evaluated by behavioral observation, nerve conduction/EMG studies, and nerve histology. Some of the crush injuries studies have identified some interesting modalities that may be potentiate motor neuron regeneration. In a study by Brushart et al,35 Sprague-Dawley rat thermal nerves were transected and repaired. This is based on the
Conclusions
The critical compression pressures that alter blood flow in the nerve are known; effects on the venous flow are observed at pressures as low as 20 mm Hg. A delayed nerve injury is observed after pressures as low as 30 mm Hg are applied to the nerve for 2 hours. These pressures initially cause capillary leakage, the accumulation of intra- and extra-neurial edema, and a persistently increased intraneurial pressure. These initial inflammatory reactions include fibrosis, demyelination, and axonal
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