PURPOSE: Wallerian degeneration (WD) is an antegrade degenerative process distal to peripheral nerve injury. Numerous genes are differentially regulated in response to the process. However, the underlying mechanism is unclear, especially the early response. We aimed at investigating the effects of sciatic nerve injury on WD via CLDN 14/15 interactions in vivo and in vitro. METHODS: Using the methods of molecular biology and bioinformatics analysis, we investigated the molecular mechanism by which claudin 14/15 participate in WD. Our previous study showed that claudins 14 and 15 trigger the early signal flow and pathway in damaged sciatic nerves. Here, we report the effects of the interaction between claudin 14 and claudin 15 on nerve degeneration and regeneration during early WD. RESULTS: It was found that claudin 14/15 were upregulated in the sciatic nerve in WD. Claudin 14/15 promoted Schwann cell proliferation, migration and anti-apoptosis in vitro. PKCα, NT3, NF2, and bFGF were significantly upregulated in transfected Schwann cells. Moreover, the expression levels of the β-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK signaling pathways were also significantly altered. CONCLUSION Claudin 14/15 affect Schwann cell proliferation, migration, and anti-apoptosis via the β-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK pathways in vitro and in vivo. The results of this study may help elucidate the molecular mechanisms of the tight junction signaling pathway underlying peripheral nerve degeneration.
Animals ; Claudins ; Nerve Regeneration ; Peripheral Nerve Injuries ; Rats ; Schwann Cells/pathology* ; Sciatic Nerve ; Wallerian Degeneration/pathology*

OBJECTIVE: To find out the incidence of reduced median conduction velocity of forearm (MNCV-F) in carpal tunnel syndrome (CTS) and to compare clinical and electrophysiologic characteristics of CTS with reduced MNCV-F and to observe the changes of reduced MNCV-F after carpal tunnel release. METHOD: One hundred and fifty nine hands with CTS are divided into two groups; MNCV-F of 50 m/sec and above as group I and that of below 50 m/sec as group II. For the electrophysiologic comparison, median sensorimotor distal latency, peak-to-peak amplitudes and abnormal spontaneous activity of abductor pollicis brevis were observed and for clinical comparison, sensorimotor symptoms, Phalen and Tinel sign were observed. Twenty four hands which had successful carpal tunnel release were examined for the changes of MNCV-F. RESULTS: The hands with reduced MNCV-F were 29 among 159 hands. Sensorimotor distal latency were significantly prolonged and sensorimotor amplitudes also significantly reduced in group II. Sensory change and Phalen signs were more frequently observed in group II. MNCV-F in group I had not changed after carpal tunnel release, but MNCV-F in group II was improved significantly. The changes MNCV-F in group II were much delayed than the improvement of parameters of distal conduction studies. CONCLUSION: The incidence of reduced MNCV-F in CTS was 18.24%. Patients with reduced MNCV-F had more severe CTS both electrophysiologically and clinically. Reduced MNCV-F had improved significantly, but there was significant time gap between the electrophysiologic improvements of distal and proximal portions of nerve. This findings may suggest that retrograde degeneration may play a partial role in reduced forearm motor nerve conduction velocity of the median nerve in CTS.
Carpal Tunnel Syndrome* ; Forearm* ; Hand ; Humans ; Incidence ; Median Nerve* ; Neural Conduction ; Retrograde Degeneration

A nerve block is an effective tool for diagnostic and therapeutic methods. If a diagnostic nerve block is successful for pain relief and the subsequent therapeutic nerve block is effective for only a limited duration, the next step that should be considered is a nerve ablation or modulation. The nerve ablation causes iatrogenic neural degeneration aiming only for sensory or sympathetic denervation without motor deficits. Nerve ablation produces the interruption of axonal continuity, degeneration of nerve fibers distal to the lesion (Wallerian degeneration), and the eventual death of axotomized neurons. The nerve ablation methods currently available for resection/removal of innervation are performed by either chemical or thermal ablation. Meanwhile, the nerve modulation method for interruption of innervation is performed using an electromagnetic field of pulsed radiofrequency. According to Sunderland's classification, it is first and foremost suggested that current neural ablations produce third degree peripheral nerve injury (PNI) to the myelin, axon, and endoneurium without any disruption of the fascicular arrangement, perineurium, and epineurium. The merit of Sunderland's third degree PNI is to produce a reversible injury. However, its shortcoming is the recurrence of pain and the necessity of repeated ablative procedures. The molecular mechanisms related to axonal regeneration after injury include cross-talk between axons and glial cells, neurotrophic factors, extracellular matrix molecules, and their receptors. It is essential to establish a safe, long-standing denervation method without any complications in future practices based on the mechanisms of nerve degeneration as well as following regeneration.
Axons ; Classification ; Denervation ; Electromagnetic Fields ; Extracellular Matrix ; Myelin Sheath ; Nerve Block ; Nerve Degeneration ; Nerve Fibers ; Nerve Growth Factors ; Nerve Regeneration ; Neuroglia ; Neurons ; Peripheral Nerve Injuries ; Peripheral Nerves ; Pulsed Radiofrequency Treatment ; Recurrence ; Regeneration* ; Sympathectomy ; Wallerian Degeneration

BACKGROUND: To understand the fundamentals of neural tissue injury, experiments on the nano-structured nerve system of animals are essential. This study was designed to reveal the nanostructure changes of an isolated ligatured rat sciatic nerve using the synchrotron small-angle X-ray scattering (SAXS) technique. METHODS: Male Sprague-Dawley rats (weighing approximately 250 grams) were used in this study. The SAXS patterns of 1 week after ligatured nerves (N = 5) and the normal sciatic nerves (N = 5) for the control were acquired after extracted approximately 15 mm before the experiment. Experiments were conducted at the 4C1 beam line at the Pohang Accelerator Laboratory in Korea. The exposure time was 60 sec, and 8 to 12 images per sample were acquired in 0.5 mm intervals, including the regions above, around and below the ligatured position. RESULTS: The periodic peaks of the myelin sheath and the interfibrillar space of collagen completely disappeared at the ligatured position. Farther from the ligatured point, weak and quite different SAXS patterns were observed for the myelin sheath and interfibrillar space. However, the collagen fiber peaks appeared at all positions, although they were weaker near the ligatured position. CONCLUSIONS: The ligature treatment totally destroyed the myelin sheath and interfibrillar space of collagen. In addition, retrograde degeneration developed 2 mm above the ligatured site. The myelin sheath and interfibrillar space of collagen were damaged 6 mm below the ligatured site. However, the collagen fiber structure was not significantly affected by the ligature, indicating a much different structural organization.
Animals ; Collagen ; Gyeongsangbuk-do ; Humans ; Korea ; Ligation ; Male ; Myelin Sheath ; Nanostructures ; Rats* ; Rats, Sprague-Dawley ; Retrograde Degeneration ; Sciatic Nerve* ; Synchrotrons*

Slowing in forearm median nerve conduction in patients with carpal tunnel syndrome(CTS) has been described. But the cause of slowing is still unclear whether it is related to a technical artifact on electrodiagnostic appr oach or pathophysiologic changes in the proximal segment of median nerve. To investigate the possible retrograde degeneration of median nerve in the forearm segment(wrist to elbow) in patients with known carpal tunnel syndrome, the median nerve conduction studies were performed in 23 normal persons as control and 25 patients with carpal tunnel syndrome. To evaluate the median nerve conductions in the forearm, the recording bar-electrode were placed at the volar aspect of the wrist and stimulating electrodes were applied at the elbow area. The mixed nerve action potentials and conduction velocities were measured. The median mixed nerve action potential(FNAP) amplitudes recorded at the wrist and motor nerve conduction velocity(MMCV) in patients with carpal tunnel syndrome patients were significantly reduced compared to those of control group(p<0.05). However, the median mixed nerve conduction velocity(FNCV) was not reduced significantly. The median mixed nerve action potential amplitudes demonstrated positive correlation with the decrease of motor and sensory action potential amplitudes and velocities. This result suggests that the retrograde degeneration progresses as the carpal tunnel syndrome progresses and the retrograde degeneration may play a major role in reduced motor nerve conduction velocity of the median nerve in the forearm. We propose that FNAP amplitude and MMCV might be used to evaluate the severity of retrograde degeneration in patients with carpal tunnel syndrome.
Action Potentials ; Artifacts ; Carpal Tunnel Syndrome* ; Elbow ; Electrodes ; Forearm ; Humans ; Median Nerve ; Neural Conduction ; Retrograde Degeneration ; Wrist

After general anesthesia with intra-venous pentothal sodium, half of the optic nerve was sectioned on both sides with special care to preserve vessels of the optic nerve. To observe retrograde degeneration of the optic nerve, the animals were sacrifised 1, 2, 3, 4, and 5 weeks after nene section. Eye ball and optic nerve was removed and fixed in 10% formalin solution. Eye baIl and optic nerve was cut and stained with Hematoxylin Eosin and Luxol Fast Blue stain for light microscopic examination. Until 2 weeks. no significant pathologic changes were observed. Specimens 3 weeks after optic nerve section showed decreased retinal ganglion cell numbers and gliosis and myelin loss in optic nerve and these changes were intensified on 4th and 5th weeks specimens. So, I observed the followings: 1. Retrograde degeneration of the optic nerve occurred simultaneously through out the length of the nerve fibers instead progressively from the cut end toward the ganglion cell. 2. The retrograde degeneration of the optic nerve started 3 weeks after section.
Anesthesia, General ; Animals ; Atrophy* ; Eosine Yellowish-(YS) ; Formaldehyde ; Ganglion Cysts ; Gliosis ; Hematoxylin ; Myelin Sheath ; Nerve Fibers ; Optic Nerve* ; Rabbits* ; Retinal Ganglion Cells ; Retrograde Degeneration ; Sodium ; Thiopental

OBJECT: There have been some controversies about the nature of peripheral neuropathy in patients with subacute comblned degeneration. Mayer concluded that the neuropathy was essentially demyelinating. And other reports which were based on pathologic or electrophyslological filldings have been saying axonopathy. We tried to find the nature of perlpheral neuropathy by doing conventional nerve conduction studies in 19 patients with subacute combined degeneration. SUBJECT AND METHOD: We included 19 patients with subacute combined degeneration, who were diagnosed by decreased serum vitamin B12(200pg/ml) and abnormal neurologic symptoms and/or signs. The patients were between 26 and 86 years of age. Eleven of them were male. We performed conventional nerve conduction studies Including H-reflex, When nerve conduction parameters deviated by more than 2SD from the normal mean value, they were consider as abnormal. RESULTS: nerve conduction studies were abnormal in 13/19. 11/13 with abnormal nerve conduction studies showed the pattern of peripheral polyneuropathy. Ten of them showed decreased amplitudes of sensory nerve action potentials or compound nerve action potentials with/wlthout mild slowing of nerve condcution. The abnormalities of the three patients with nerve conduction parameters of demyelinating range were confined to the distal segments of the median nerves. CONCLUSION: We thought that the results of the nerve conduction studies of our cases were compatible with axonopathy rather than demyelinopathy as a principal ]esion of the peripheral nervous system.
Action Potentials ; H-Reflex ; Humans ; Male ; Median Nerve ; Neural Conduction* ; Neurologic Manifestations ; Peripheral Nervous System ; Peripheral Nervous System Diseases ; Polyneuropathies ; Subacute Combined Degeneration ; Vitamins

Recently nerve entrapments or nerve root compressions are common clinical symdromes. However, a clear understanding of both pathophysiological and morphological changes is lacking and it may not be completely established in the experimental model for chronic nerve compression, compared with a surprising review of peripheral nerve exposed to various acute damage. Adult Sprague-Dawley rats weighing 250 to 300g were used as the experimental model to elucidate histopathological changes in chronic nerve compression, which were produced by banding the sciatic nerve(normally 1.2mm in diameter) with the length of 1cm silastic tubings with inner diameter, 0.6mm(Group I), 0.9mm(Group II) and 1.5mm(Group III) in each. Specimens were obtained for light and electron microscopic studies postoperatively at 1 and 3 months following by nerve conduction study. Grossly in group I, the sciatic nerve was compressed to approximately 50% of its normal in cuff area and in thin strand on distal part at 1 month and more progressed at 3 months. The sciatic nerve of group II demonstrated 75% of control and distal part in 50% compression at 1 month, but the nerve seemed not to be affected by tubing. Light microscopic findings revealed Wallerian degeneration and diminished large myelinated fiber particularly in the periphery of nerves with 34% of transverse nueral percentage in group I at postoperative 1 month. Above findings were progressed to epineurial scarring and fibrosis at 3 months. There were marked diminution and deformity in large myelinated fiber in group II, but it was not more severe than the ones of group I. Electron microscopic findings in this group revealed the appearance of small regenerating unit clusters and thinly myelinated fibers. In group III, histological findings were not much different from that of normal nerve. Nerve conduction study revealed the decrease in conduction velocity to mean 10 M/sex in group I at 1 month and no electrical conduction at 3 months. In group II, diminution of conduction velocity in 73% of normal range at 1 month was noted, and 82% at 3 months. These findings explain correspondingly the histopathological changes in part of chronic nerve entrapment syndromes and appeal the need of further investigation in this experimental model.
Adult ; Cicatrix ; Congenital Abnormalities ; Fibrosis ; Humans ; Models, Theoretical ; Myelin Sheath ; Nerve Compression Syndromes ; Neural Conduction ; Peripheral Nerves ; Radiculopathy ; Rats, Sprague-Dawley ; Reference Values ; Sciatic Nerve ; Wallerian Degeneration

It is well known that leprosy bacilli have a special affinity for peripheral nerves, especially Schwann cells but also including perineurial cells and endothelial cells of endoneurial blood vessels. The Schwann cells, after invasion by and saturation with multiplied M. leprae, are destroyed and segmental demyelination and Wallerian degeneration follow. This condition, then is known to be the main neural pathogenosis in early leprosy. It is rarely observed that the progressive paralysis occurs in arrested leprosy patients under adequate treatment. Therefore, the authors performed a histopathologic study of 80 peripheral nerves obtained from the autopsies of 10 old lepromatous leprosy patients including two active cases whose disease durations ranged from 6 to 49 years. The authors arbitrarily divided all the histopathologic findings into 5 grades on the basis of 1) difference in pathological findings in relation to disease duration and bacterial index, and 2) the coexistence of various lesions within the same nerve trunk. As the disease progresses the destroyed nerve fibers are replaced by fibrous and granulation tissue while the perineurial reaction increases. The cellular reaction is minimal in the low grades. There is a slightly early increased vasculature probably due to M. leprae and later a more pronounced increase with large vessels indicating the presence of the granulation process. There is minimum to moderate interfascicular reaction throughout every grade, ie. increased cellularity, vessel wall thickening and increased numbers of vessels with fibrosis. Acid-fast bacilli were demonstrated only in the active cases. The coexistence of different fascicular lesions within the same nerve trunk of peripheral nerve and of femoral nerves mear the spinal cord indicates the presence of some perineurial inhibitory effect which, while promoting the centripetal spread of, prevents the transfascicular spread of M. leprae for some time.
Autopsy ; Blood Vessels ; Demyelinating Diseases ; Endothelial Cells ; Femoral Nerve ; Fibrosis ; Granulation Tissue ; Humans ; Leprosy* ; Leprosy, Lepromatous ; Nerve Fibers ; Paralysis ; Peripheral Nerves* ; Schwann Cells ; Spinal Cord ; Wallerian Degeneration

Neuropathy is a serious and disabling complication that contributes to increased morbidity and mortality in diabetic patients. There is progressive distal to proximal axonal atrophy that ultimately leads to Wallerian degeneration. This study was performed to identify the effect of soy bean on diabetic neuropathy using morphometry. Male Sprague-Dawley rats were grouped into control, diabetic with red chow diet and diabetic with soy bean diet. The myelinated nerve fibers were counted and fiber size distributions were evaluated in each group at 4 and 8 weeks, respectively. Diabetic neuropathy didn't develop in streptozotocin-induced diabetic rats at four weeks. At 8 weeks, the myelinated nerve fiber in diabetic with soy bean diet was larger in number than that in diabetic to which did not be administered insulin. The number of myelinated nerve fiber was not different between diabetic group with insulin and without insulin. Mean myelinated nerve fiber size was smaller in diabetic with soy bean diet than diabetic with red chow diet and control. Histogram of fiber size distribution was shifted to left in diabetic with red chow and soy bean diet groups compared to control. Light and electron microscopic findings showed marked degeneration of nerve fibers in diabetic with red chow diet but preservation in diabetic with soy bean diet. The level of glucose and HbA1c was lower in diabetic with soy bean diet than red chow diet. Soy bean could be effective in the protection of neuropathy induced by diabetes mellitus.
Animals ; Atrophy ; Axons ; Diabetes Mellitus ; Diabetic Neuropathies* ; Diet* ; Glucose ; Humans ; Insulin ; Male ; Microscopy, Electron ; Mortality ; Nerve Fibers ; Nerve Fibers, Myelinated ; Rats* ; Rats, Sprague-Dawley ; Soybeans* ; Streptozocin ; Wallerian Degeneration