No abstract available.
Brain ; Brain Injuries ; Spinal Cord ; Wallerian Degeneration

New genetic and environmental studies of Parkinson's disease have revealed early problems in synaptic function and connectivity indicating that axonal impairment may be an important hallmark in this disorder. Since many studies suggest that axonal dysfunction precedes cell body loss, it is critical to target axons with treatments aimed at preserving "connectivity" as well as to develop and verify "biomarkers" with which to assess disease progression and drug efficacy.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Axons ; Disease Progression ; Mitochondria ; Parkinson Disease ; Wallerian Degeneration

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*

Wallerian degeneration is well known as the anterograde degeneration of axon and their accompanying myelin sheath from injury to the proximal portion of the axon or its cell body. The most common cause of wallerian degeneration is cerebral infarction. Authors experienced three patients with old hemispheric infarct with typical wallerian degeneration in the brain stem, which was demonstrated by magnetic resonance imaging (MRI) in two cases and CT in one case. This report demonstrates the wallerian degeneration in the corticospinal tract on the MRI and CT with the brief review of the literatures.
Axons ; Brain Stem ; Brain* ; Cell Body ; Cerebral Infarction ; Humans ; Magnetic Resonance Imaging* ; Myelin Sheath ; Pyramidal Tracts ; Wallerian Degeneration*

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

Myelinated Schwann cells in the peripheral nervous system express the p75 nerve growth factor receptor (p75NGFR) as a consequence of Schwann cell dedifferentiation during Wallerian degeneration. p75NGFR has been implicated in the remyelination of regenerating nerves. Although many studies have shown various mechanisms underlying Schwann cell dedifferentiation, the molecular mechanism contributing to the re-expression of p75NGFR in differentiated Schwann cells is largely unknown. In the present study, we found that lysosomes were transiently activated in Schwann cells after nerve injury and that the inhibition of lysosomal activation by chloroquine or lysosomal acidification inhibitors prevented p75NGFR expression at the mRNA transcriptional level in an ex vivo Wallerian degeneration model. Lysosomal acidification inhibitors suppressed demyelination, but not axonal degeneration, thereby suggesting that demyelination mediated by lysosomes may be an important signal for inducing p75NGFR expression. Tumor necrosis factor-alpha (TNF-alpha) has been suggested to be involved in regulating p75NGFR expression in Schwann cells. In this study, we found that removing TNF-alpha in vivo did not significantly suppress the induction of both lysosomes and p75NGFR. Thus, these findings suggest that lysosomal activation is tightly correlated with the induction of p75NGFR in demyelinating Schwann cells during Wallerian degeneration.
Axons ; Cell Dedifferentiation ; Chloroquine ; Demyelinating Diseases ; Lysosomes ; Myelin Sheath ; Nerve Growth Factor ; Peripheral Nervous System ; RNA, Messenger ; Schwann Cells ; Tumor Necrosis Factor-alpha ; Wallerian Degeneration

The purposes of this study were to describe the magnetic resonance(MR) manifestations of wallerian degeneration occurring above and below a spinal cord injury site, to determine the post-injury time interval when the wallerian degeneration becomes evident in MR images, and to correlate the MR findings with post mortem histopathology. Twenty-three postmortem spinal cords, all from patients with cervical(14), thoracic(5), and lumbar(4) cord injuries, were studied with axial TI-and T2-weighted spin-echo MR imaging. Injury to death intervals varied from 8 days to 22 years. We examined these specimen for abnormal cord contour and alteration of signal above and below the injury site. Histological studies of these cords with axon, myelin, and connective tissue stains were performed at levels equivalent to the MR sections. Studies using plastic embedded sections and antibodies to Glial Fibrillary Acetic Protein(GFAP) were also performed on some of the above cords. Pathological-imaging correlations were made. MR images of the cord specimen showed increased signal intensity in the dorsal columns above the injury level as well as in the lateral corticospinal tracts below the injury level in all cases in which cord injury had occurred seven or more weeks premortem. In one case where cord injury had occurred eight days prior to death the MR showed no signal abnormalities, histological analysis showed evidence of early wallerian degeneration in the dorsal columns above the lesion but no change was detected in the lateral columns below the lesion. After 12 days, early stage wallerian degeneration was detected by histological examination in both the lateral columns below the lesion and in the dorsal columns above the lesion. Wallerian degeneration in spinal cords, as demonstrated by histological examination, was identified on MR as areas of increased T2 weighted signal intensity site in the dorsal column above the injury site and in the corticospinal tracts below the injury site in all specimen in which the injury-to-death interval was greater than 7 weeks. The ability to recognize wallerian degeneration on MR allows a more comprehensive analysis of the injury, explains abnormal MR signals at sites that are remote from the epicenter of injury, and may be helpful in the assessing of results of therapeutic interventions.
Antibodies ; Axons ; Coloring Agents ; Connective Tissue ; Humans ; Magnetic Resonance Imaging ; Myelin Sheath ; Plastics ; Pyramidal Tracts ; Spinal Cord Injuries* ; Spinal Cord* ; Wallerian Degeneration*

BACKGROUND: Diffusion tensor MRI (DTI) is a new imaging technique and enables us to analyze the structural damage of fiber pathways and to monitor the time course of Wallerian degeneration of the pyramidal tract in stroke patients. We used DTI to investigate structural changes of the infarct area and the associated descending corticospinal tract in patients with subcortical infarct. METHODS: We examined 24 consecutive patients who presented with acute single cerebral infarct in the subcortical area and who also had undergone an MRI study within 7 days after symptom onset. Clinical outcome was assessed using the National Institutes of Health Stroke Scale (NIHSS) at admission, 7 days, 14 days and 30 days and modified Rankin Scale (mRS) at admission and 30 days. Each of the indices was achieved by post processing the acquired DTI data and correlated with the NIHSS. RESULTS: In infarct region, fractional anisotropy (FA) was significantly decreased compared with matched-contralateral regions (0.39 vs. 0.53, p<0.001). In the distal to the infarct, FA was significantly decreased at internal capsule (0.62 vs. 0.64, p=0.019), not at pons (0.51 vs. 0.53, p=0.103). The decrease of anisotropy at infarct region correlated positively with the NIHSS at 7, 14 and 30 days and mRS at 30 days after stroke, but the decrease of anisotropy at internal capsule did not correlate with the NIHSS. CONCLUSIONS: This study shows the potential of DTI to detect and monitor the structural degeneration of fiber pathways and to establish the prognosis in patients with acute subcortical cerebral infarct.
Anisotropy ; Cerebral Infarction* ; Diffusion* ; Humans ; Internal Capsule ; Magnetic Resonance Imaging* ; National Institutes of Health (U.S.) ; Pons ; Prognosis ; Pyramidal Tracts ; Stroke ; Wallerian Degeneration

The current understanding of the pathophysiology of mild traumatic brain injury (mTBI) is, without doubt, incomplete. Nevertheless, we tried to summarize the state-of-the-art explanation of how the brain is continuously injured even after a single impact. We also reviewed the real struggle of diagnosing mTBI, which culminated in showing the potential of blood-based biomarkers as an alternative or complementary way to overcome this difficulty. Pathophysiology of mTBI is subdivided into primary and secondary injuries. Primary injury is caused by a direct impact on the head and brain. Secondary injury refers to the changes in energy metabolism and protein synthesis/degradation resulting from the biochemical cascades as follows; calcium influx, mitochondrial dysfunction, fractured microtubules, and Wallerian degeneration, neuroinflammation, and toxic proteinopathy. Since the diagnosis of mTBI is made through the initial clinical information, it is difficult and inaccurate to diagnose mTBI without the absence of a witness or sign of head trauma. Blood-based biomarkers are expected to play an important role in diagnosing mTBI and predicting functional outcomes, due to their feasibility and the recent progress of targeted proteomics techniques (i.e., liquid chromatography tandem mass spectrometry [LC-MS/MS]).
Biomarkers* ; Brain ; Brain Concussion ; Brain Injuries* ; Calcium ; Chromatography, Liquid ; Craniocerebral Trauma ; Diagnosis ; Energy Metabolism ; Head ; Microtubules ; Proteomics ; Tandem Mass Spectrometry ; Wallerian Degeneration