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Children, in contrast to adults, show an excellent clinical recovery after a peripheral nerve injury, which may be explained by better peripheral nerve regeneration and a superior plasticity in the young brain. Our aim was to study the long-term electrophysiological outcome after nerve repair in children and young adults and to compare it with the clinical outcome. Forty-four patients, injured at an age younger than 21 years, were assessed by electrophysiology (amplitude, conduction velocity and distal motor latency) at a median of 31 years after a complete median or ulnar nerve injury at the level of the forearm. Electrophysiological evaluation showed pathology in all parameters and in all patients, irrespective of age at injury. No significant differences were observed in the electrophysiological results between those injured in childhood, that is, before the age of 12 years, and those injured in adolescence, that is, between 12 and 20 years of age. In contrast, the clinical nerve function was significantly better for those injured in childhood (87% of complete recovery, P=0.002) compared with those injured in adolescence. We conclude that the mechanism behind the superior clinical outcome in children is not located at the periphery, but is explained by cerebral plasticity.

Phosphorylation of extracellular-signal-regulated kinase 1/2 (p-ERK 1/2) was investigated by immunohistochemistry at 30 min, 1 h, and 48 h after nerve transection in the sciatic nerve of healthy and diabetic [streptozotocin (STZ)-induced diabetes mellitus and BioBreeding (BB; i.e. DR.lyp/lyp or BBDP)] rats. Transection injury increased the intensity of p-ERK 1/2 in nerve stumps at all time points. Staining was confined to Schwann cells with occasional faint staining in single axons. In diabetic rats, a lower intensity of p-ERK 1/2 was found at 1 and 48 h in the distal and proximal nerve stumps compared with healthy rats. STZ-induced diabetic rats were not different from BB rats. p-ERK 1/2 is activated differentially in Schwann cells after nerve injury in diabetic rats, whereas activation in STZ-induced diabetic rats did not differ from BB rats.

The aim was to investigate the relation between axonal outgrowth (neurofilaments) and Schwann cell activation (activating transcription factor 3) and apoptosis (caspase 3) 10 days after nerve repair with no, minor (3 mm defect) and moderate (6 mm defect) tension in rat sciatic nerve using immunohistochemistry. After repair with no tension, axons grew 11.75 mm, but repair with minor and moderate tension impaired axonal outgrowth by 29 and 48%, respectively, with a reduced number of activating transcription factor 3 stained and an increased number of caspase 3 stained Schwann cells. Axonal outgrowth correlated with activation of and inversely with apoptosis of Schwann cells. Tension induces impaired activation of Schwann cells, and a higher amount of apoptotic Schwann cells, with a subsequent deteriorated axonal outgrowth.

N-CAM, expressed by non-myelinating Schwann cells, was investigated by immunohistochemistry in transected rat femoral nerves, which were repaired either using a straight or a crossed over technique. N-CAM staining covered 30 and 11% of the cross-sectional area of sensory and motor branches, respectively, in uninjured nerves. After 3 days there was a transient smaller area of N-CAM staining following both the repairs. After a straight repair N-CAM area increased to the control values in both branches. In contrast, a crossed over repair resulted in a continuous increase of N-CAM in the motor branch, whereas the area in the sensory branch returned slowly to control values. N-CAM is influenced by an intentionally misdirected outgrowth of motor and sensory axons after nerve repair.

Expression of transcription factor ATF3 in sensory neurons in dorsal root ganglion and in Schwann cells in sciatic nerve of diabetic (BB and Goto-Kakizaki rats; experimental models of types 1 and 2 diabetes, respectively) and healthy rats were examined by immunocytochemistry after nerve compression (silicone tube) for 3, 6 or 14 days. ATF3-stained sensory neurons in dorsal root ganglia and Schwann cells at compression site were more frequent in diabetic BB rats. Decompression of nerves in Goto-Kakizaki rats did not reduce number of ATF3-stained cells. Diabetes (BB; i.e. type 1) confers on the peripheral nerve an increased susceptibility to nerve compression indicated by an increased expression of stained ATF3 neurons and Schwann cells.

Activation of extracellular-signal-regulated kinase-1/2 (Erk1/2) by phosphorylation to p-Erk1/2, and proliferation of Schwann cells were investigated in the rat sciatic nerve by immunohistochemistry. Axotomy in vivo and culturing of nerve segments in vitro resulted in a rapid (30 min) increase of p-Erk1/2 in Schwann cells with peaks at 2 and 24 h. Proliferation measured by bromodeoxy uridine incorporation and immunostaining in vivo and in vitro 48 h after axotomy showed an increase in Schwann cell proliferation at the sites of Erk1/2 activation. The Erk1/2 inhibitor U0126 inhibited both the increase in p-Erk1/2 and the bromodeoxy uridine incorporation. We suggest that an increase in p-Erk1/2 is required for nerve injury-induced proliferation of Schwann cells.

Galanin is probably involved in nociceptive sensory processing in spinal cord. We investigated whether a common injury, peripheral nerve compression, induced up-regulation of galanin (immunocytochemistry) in sensory neurons in rats 6 or 14 days post-injury and compared the response with other nerve injuries. Sciatic nerve compression increased the number of galanin positive sensory neurons as compared to uninjured and contralateral dorsal root ganglia. Complete transection was more efficient than a partial transection and a slight compression injury as an inducer of galanin. Mainly small diameter sensory neurons became positive but also some large diameter neurons. We conclude that nerve compression up-regulates galanin in sensory neurons. The extent of the induction could be related to the severity of nerve injury.

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.

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.

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.

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.