Cell activation and nerve regeneration following peripheral nerve injury

The effect of short time vibration exposure and tourniquet compression on nerve regeneration in rats was studied with special reference to cell activation. One of the hindlimbs was conditioned by either vibration exposure (5 hours / day - 5 consecutive days) or compression (150-300 mmHg for 30-120 minutes), which was followed by a recovery period of 0-7 days. Test crush lesions or a transplantation of a conditioned nerve segment into a freshly made gap in the contralateral nerve (and vice versa after vibration), were performed. Axonal regeneration distances were measured after an additional 3-8 days. Furthermore the reaction of neuronal cellbodies, in the dorsal root ganglia, and non-neuronal cells was studied following compression. Vibration exposure, and tourniquet compression in particular, increased axonal regeneration lengths after both test crush lesions and transplantation (up to 36%). This so called conditioning effect, which may be regarded as a sign of injury, was in one experiment prevented by treatment with D600, a calcium channel blocker. The non-neuronal cells, which were mainly Schwann cells, increased their proliferation following compression along with an upregulation of the low affinity nerve growth factor receptor (p75). The neuronal cellbodies responded to compression by increased expression of the C-terminal flanking peptide of Neuropeptide Y (CPON). Thus, tourniquet compression and vibration exposure, which are non-invasive methods, can increase the regenerative capacity of neurons. This requires activation of both Schwann cells and neuronal cellbodies. Conversely, the observed effect of such treatments may be regarded as a potentially harmful alarm reaction in the peripheral nervous system. Whether D600 prevents nerve injury caused by vibration exposure or compression remains to be investigated

Reduction of proliferating non-neuronal cells in dried nerve segments partly impairs nerve regeneration

To determine whether drying of nerve grafts can affect axonal outgrowth and proliferation of non-neuronal cells, nerve segments dried for 0-60 min were used as nerve grafts to bridge a gap in transected rat sciatic nerves. Axonal outgrowth was measured by pinch reflex test and confirmed by immunocytochemical staining of neurofilaments. The proliferation of non-neuronal cells was measured by incorporation of BrdU in the dried nerve segments. Drying of the nerve segment for 60 min reduced the length of axonal outgrowth to 66 and 76% 3 and 6 days, respectively, after the grafting procedure. At that time point the number of proliferating cells was reduced by 51%. It is concluded that the number of proliferating non-neuronal cells is reduced in dried nerve segments which only partly impairs axonal outgrowth. Factors other than Schwann cells are probably important for an optimal mileue for regeneration in nerve grafts

Nerve regeneration enhancement by tourniquet

The use of tourniquet compression as a non-invasive method to enhance axonal regeneration was assessed in the rat sciatic nerve. One hind limb of the rat was subjected to compression by a tourniquet set at 300 mmHg for 30 or 120 min followed by bilateral test crush lesions performed either directly or after a conditioning interval of 3 or 6 days, with the non-compressed side serving as a control. Axonal regeneration distances were evaluated after 3 days by the pinch reflex test. We found that compression caused an increased outgrowth length of sensory axons compared to the controls. The effect was most obvious after 120 min of compression with a conditioning interval of 6 days. Tourniquet compression has a conditioning lesion effect on peripheral nerve and may enhance nerve regeneration

Tourniquet compression: a non-invasive method to enhance nerve regeneration in nerve grafts.

One hindlimb of a rat was subjected to tourniquet compression (150, 200 and 300 mmHg; 2 h). After 6 days a 10 mm sciatic or tibial nerve graft from the compressed limb was sutured to bridge a 3-4 mm gap in the sciatic nerve of the non-compressed limb. The distances of regenerating sensory axons were measured 6 days post surgery (tibial grafts, 8 days). Compression at 200 and 300 mmHg led to significantly longer regeneration distances than those seen in controls. Incorporation of BrdU and expression of p75 receptor by non-neuronal cells (Schwann cells) in sciatic nerves 6 days after compression (150 and 300 mmHg; 2 h) was also increased as a sign of Schwann cell activation. Tourniquet compression may be used as a non-invasive method to enhance nerve regeneration in nerve grafts

C-terminal flanking peptide of neuropeptide Y in DRG following nerve compression

The C-terminal flanking peptide of neuropeptide Y (CPON) was studied in dorsal root ganglia (DRG) by immunocytochemistry after different recovery periods (3, 6,14 and 28 days) following tourniquet compression of the rat hindlimb (sciatic nerve; 150 or 300 mmHg; 2 h). Compression induced a transient increase in the number of CPON-positive DRG-neurons (the contralateral uninjured side was devoid of CPON-positive cells). The compression-induced increase in CPON was less than that observed in separate rats subjected to sciatic nerve transection. The results show that compression induces regenerative changes in peripheral neurons and that such an injury of the nerve trunk is not limited to the site of the compression but results in the activation of the entire neuron

Long-term results of syndactyly correction by the trilobed flap technique focusing on hand function and quality of life.

Syndactyly is usually corrected surgically during the first years of life. The trilobed flap, a surgical method that does not require skin grafting, was developed in the 1990s and the short-term results were comparable with previously reported techniques. Here we report on long-term outcomes, focusing on how children perceive their hand function and quality of life when they grow up. A total of 19 patients (29 web spaces) were operated on between 1990 and 2000, and followed-up 16 years later with questionnaires and clinical tests. The patients reported low QuickDASH scores, normal sensibility and dexterity, and minor cold intolerance. Only two reoperations, due to early web creep, were needed. The condition minimally affected the choice of occupations, leisure activities and perceptions of appearance. The trilobed flap technique for release of syndactyly provides a good long-term outcome with good hand function and minimal impact on the quality of life

Experimental nerve compression and upregulation of CPON in DRG

Expression of C-terminal flanking peptide of neuropeptide Y (CPON) in DRG and cell proliferation (incorporation of BrdU) in sciatic nerve of rats following chronic nerve compression (silicone tubes with different internal diameters) was studied by immunocytochemistry. An increased number of CPON-positive neurons and cells incorporating BrdU was induced on the compressed side, most pronounced when a tight tube was used, while no cells expressed CPON or BrdU in intact nerves. The increase was transient and declined with time. Nerve compression induces transient cell proliferation in the nerve and expression of CPON in nerve cell bodies, but this is of a lesser magnitude than those following nerve transection

S-100beta stimulates neurite outgrowth in the rat sciatic nerve grafted with acellular muscle transplants

S-100beta promotes neurite extension in vitro and motoneuron survival in the chicken embryo. We demonstrate here that local administration of S-100beta stimulates the sciatic nerve regeneration into acellular muscle grafts. Normally there is a 8-10 day delay in the regeneration of axons into such grafts. Local administration of S-100beta (0.5-1.0 microg/h) significantly stimulated regeneration into the grafts. In S-100beta treated grafts, the regeneration distance was increased with a factor of about 2.3 times as compared to vehicle treated grafts. The distance of regeneration was monitored with pinch test which detects sensory axons. Regenerating axons were growing outside the necrotic muscle cells as revealed with immunohistochemistry for the neurofilament light weight polypeptide. S-100beta was demonstrated immunocytochemically in motor neurons of the rat lumbar spinal cord and in large and medium sized neurons of the dorsal root ganglia. The results suggest that S-100beta is a physiological growth factor for peripheral nerve axons