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*

In this study, the effects of Radio Electric Asymmetric Conveyer (REAC), a non-invasive physical treatment, on neuroinflammatory responses in a mouse model of parkinsonism induced by intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), were investigated in vivo. We found that the REAC tissue optimization treatment specific for neuro-regenerative purposes (REAC TO-RGN-N) attenuated the inflammatory picture evoked by MPTP-induced nigro-striatal damage in mice, decreasing the levels of pro-inflammatory molecules and increasing anti-inflammatory mediators. Besides, there was a significant reduction of both astrocyte and microglial activation in MPTP-treated mice exposed to REAC TO-RGN-N. These results indicated that REAC TO-RGN-N treatment modulates the pro-inflammatory responses and reduces neuronal damage in MPTP-induced parkinsonism.
Animals ; Corpus Striatum ; pathology ; Electric Stimulation ; methods ; Inflammation ; pathology ; Male ; Mice ; Nerve Degeneration ; pathology ; Nerve Regeneration ; physiology ; Parkinsonian Disorders ; pathology

Hypertrophic olivary degeneration resulting from lesions of the dento-rubro-olivary pathway, also called Guillain-Mollaret-triangle, has been described previously in a number of cases. Reports about bilateral hypertrophic olivary degeneration of the inferior olivary nuclei are very limited, and the magnetic resonance imaging findings of hypertrophic olivary degeneration in Wilson disease have not yet been described to the best of our knowledge. Herein, we present the first report of bilateral hypertrophic olivary degeneration diagnosed by magnetic resonance imaging in a patient suffering from Wilson disease.
Diagnosis, Differential ; Hepatolenticular Degeneration/*pathology ; Humans ; Hypertrophy/pathology ; Magnetic Resonance Imaging/*methods ; Male ; Nerve Degeneration/*pathology ; Olivary Nucleus/*pathology ; Young Adult

OBJECTIVETo investigate systematically Schwann cell apoptosis in Wallerian-degenerated sciatic nerve of the rat, and evaluate its time-related feature.

METHODSNinety-five SD rats were divided randomly into one normal group (8 rats) and 11 experimental groups (66 rats, 6 in each). Both hind legs of each rat in experimental groups were randomly divided into test leg (sciatic nerve transected) and control one (nerve uninjured). All test legs constituted a test group and all control legs constituted a control one. After operation, all rats were respectively sacrificed at 1 h, 6 h, 12 h, 24 h, 2 d, 3 d, 4 d, 8 d, 14 d, 21 d, and 30 d. We analyzed the specimens of mid-distal sciatic nerve, especially the morphological changes of the nerve, the different expression levels of S-100 protein and apoptosis-related proteins such as Bcl-2, Bax, and Fas in Schwann cells. The TUNEL method was used to detect the apoptotic rate of Schwann cells.

RESULTS(1) The test group showed Wallerian degeneration. The number of Schwann cells began to decrease at 24 h, obviously decreased on day 3 and 4, then began to increase from day 8 and formed Bungner belt after 14 days. (2) Schwann cells generally expressed S-100 at a low level in all groups. The control group was not significantly different from the normal group. The test group had statistical significance at 1 h and day 21. (3) As an inhibitory gene protein of Schwann cell apoptosis, Bcl-2 positive rates in the control and test groups apparently elevated and were statistically different from the normal group. (4) As a promotive gene protein of Schwann cell apoptosis, the control and test groups expressed Bax at a high level and were statistically different from the normal group. (5) As a promotive gene protein of Schwann cell apoptosis, Fas positive rate in control group was slightly elevated, but had no statistical significance compared with the normal group. Fas positive rate in test group continuously elevated in a fluctuant way, with highly statistical significance compared with the normal group. (6) TUNEL detection further proved that Schwann cell apoptosis rarely existed in the normal group, and the left sciatic nerve had no statistical significance compared with the right sciatic nerve. While the test group showed lots of apoptotic nuclei at 6 h, 2 d, 4 d, and 21 d. It had highly statistical significance compared with the normal group.

CONCLUSIONSSchwann cell apoptosis does exist in Wallerian-degenerated sciatic nerve of the rat after transection. Schwann cell apoptosis and its apoptotic genes expression have a time-related feature.

Analysis of Variance ; Animals ; Apoptosis ; Female ; In Situ Nick-End Labeling ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Schwann Cells ; pathology ; Sciatic Nerve ; pathology ; Staining and Labeling ; Wallerian Degeneration ; pathology

INTRODUCTIONMotor neuron damage and cortical spinal tract (CST) degeneration in amyotrophic lateral sclerosis (ALS) are difficult to visualise and quantify on conventional magnetic resonance imaging (MRI).

CLINICAL PICTUREWe studied 8 ALS patients and 12 normal volunteers using diffusion tensor imaging (DTI) and fibre tractography using fibre assignment by continuous tracking (FACT) to study the fibres of the CST and the posterior thalamic radiation (PTR), a nonmotor tract.

OUTCOMEFibre tractography was successfully performed in all normal volunteers and all patients except 1. The fibre bundles of the CST, but not the PTR, were significantly reduced (P <0.05) in patients compared to normal volunteers.

CONCLUSIONFibre tractography can visualise axonal degeneration in the CST and may provide supplementary information about upper motor neuron disease in ALS patients.

Amyotrophic Lateral Sclerosis ; pathology ; Case-Control Studies ; Diffusion Magnetic Resonance Imaging ; Echo-Planar Imaging ; Female ; Humans ; Male ; Middle Aged ; Nerve Degeneration ; pathology ; Pyramidal Tracts ; pathology

A subset of patients of amyotrophic lateral sclerosis (ALS) present with mutation of Cu/Zn superoxide dismutase 1 (SOD1), and such mutants caused an ALS-like disorder when expressed in rodents. These findings implicated SOD1 in ALS pathogenesis and made the transgenic animals a widely used ALS model. However, previous studies of these animals have focused largely on motor neuron damage. We report herein that the spinal cords of mice expressing a human SOD1 mutant (hSOD1-G93A), besides showing typical destruction of motor neurons and axons, exhibit significant damage in the sensory system, including Wallerian-like degeneration in axons of dorsal root and dorsal funiculus, and mitochondrial damage in dorsal root ganglia neurons. Thus, hSOD1-G93A mutation causes both motor and sensory neuropathies, and as such the disease developed in the transgenic mice very closely resembles human ALS.
Amyotrophic Lateral Sclerosis/enzymology/*pathology ; Animals ; Axons/*pathology ; Disease Models, Animal ; Ganglia, Spinal/pathology ; Humans ; Mice ; Mice, Transgenic ; Mitochondria/pathology ; Motor Neurons/metabolism/pathology ; Mutation ; Nerve Degeneration/*pathology ; Sensory Receptor Cells/*pathology ; Spinal Cord/*pathology ; Superoxide Dismutase/genetics/*physiology

Animals ; Antidepressive Agents ; pharmacology ; Brain-Derived Neurotrophic Factor ; metabolism ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Depression ; metabolism ; pathology ; physiopathology ; Hippocampus ; metabolism ; pathology ; physiopathology ; Humans ; Nerve Degeneration ; physiopathology ; Nerve Regeneration ; drug effects ; Neurons ; pathology ; Stress, Psychological ; metabolism ; pathology ; physiopathology

In order to investigate the neurotoxicity of lipopolysaccharide (LPS) on the dopaminergic neurons of substantia nigra and the pathogenesis of Parkinson disease, LPS was stereotaxically infused into substantia nigra (SN). At different dosages and different time points with 5 microg LPS, the damage of the dopaminergic neurons in SN was observed by using tyrosine-hydroxylase (TH) immunohistochemical staining. The results showed that 14 days after injection of 0.1 microg to 10 microg LPS into the rat SN, TH-positive (TH+) neurons in the SN were decreased by 5%, 15%, 20%, 45 %, 96% and 99% respectively. After injection of 5 microg LPS, as compared with the control groups, TH+ neurons began to decrease at 3rd day and obviously decrease at 14th day, only 5% of total cells, and almost disappeared 30 days later. The results suggested that LPS could induce the degeneration of dopaminergic neurons in the SN in a dose- and time-dependent manner.
Animals ; Dopamine ; metabolism ; Dose-Response Relationship, Drug ; Female ; Lipopolysaccharides ; toxicity ; Nerve Degeneration ; Neurons ; pathology ; Parkinson Disease, Secondary ; chemically induced ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; pathology

In order to investigate the neurotoxicity of lipopolysaccharide (LPS) on the dopaminergic neurons of substantia nigra and the pathogenesis of Parkinson disease, LPS was stereotaxically infused into substantia nigra (SN). At different dosages and different time points with 5 microg LPS, the damage of the dopaminergic neurons in SN was observed by using tyrosine-hydroxylase (TH) immunohistochemical staining. The results showed that 14 days after injection of 0.1 microg to 10 microg LPS into the rat SN, TH-positive (TH+) neurons in the SN were decreased by 5%, 15%, 20%, 45 %, 96% and 99% respectively. After injection of 5 microg LPS, as compared with the control groups, TH+ neurons began to decrease at 3rd day and obviously decrease at 14th day, only 5% of total cells, and almost disappeared 30 days later. The results suggested that LPS could induce the degeneration of dopaminergic neurons in the SN in a dose- and time-dependent manner.
Dopamine/metabolism ; Dose-Response Relationship, Drug ; Lipopolysaccharides/*toxicity ; *Nerve Degeneration ; Neurons/pathology ; Parkinson Disease, Secondary/*chemically induced ; Random Allocation ; Rats, Sprague-Dawley ; Substantia Nigra/*pathology

STUDY DESIGN: The ingrowth of the nociceptive nerve ending into intervertebral disc was examined using immunohistochemistry and quantified using western blotting. OBJECTIVES: To determine if the nociceptive nerve innervates into the intervertebral discs of internal disc disruption (IDD). SUMMARY AND LITERATURE REVIEW: Nociceptive nerve ending and vessel ingrowth into intervertebral disc is associated with IDD and HNP. Substance P is a neurotransmitter that is found in the nociceptive nerve endings. Immunohistochemistry has confirmed the presence, and western blot has isolated the target. The localization of novel nociceptive innervation, and a quantitative comparison was made according to the original pathology is of interest. MATERIALS AND METHODS: 10 specimens of intervertebral disc were collected from IDD during total disc replacement surgery , and another 10 specimens of intervertebral disc from HNP were collected during discectomy. The control samples of intervertebral disc were obtained from 3 adolescent patients with idiopathic scoliosis, and 2 patients with a lumbar bursting fracture. Standard immunohistochemical techniques were used to test for the nociceptive neurotransmitter (substance P), which is a protein expressed during axonogenesis (growth-associated protein 43, GAP43), and a general nerve marker (protein gene produce 9.5, PGP9.5). The expression of substance P protein was quantified using western blot for its polyclonal antibody. RESULTS: In IDD (n=10), substance P was expressed in 6 cases of outer annulus fibrosus (AF), 5 cases of inner AF, and 3 cases of nucleus pulposus (NP). In HNP (n=10), substance P was expressed in 4 cases of outer AF, 3 cases of inner AF, and 2 cases of NP. In the control group, only 2 cases expressed substance P in outer AF. GAP43 was only positive in outer AF as follows: IDD 3 cases, HNP 1 case, and control 1 case. None of the specimens showed localized PGP 9.5. Substance P was localized significantly in larger quantities in IDD than in the control group (p=0.002). In HNP, the expression level was larger than the control and lower than the IDD group but this was not statistically significant (p=0.158, p=0.108). CONCLUSIONS: Innervation of nociceptive nerve endings was identified at the degenerative intervertebral disc of IDD, which may contribute to back pain.
Adolescent ; Back Pain ; Blotting, Western ; Diskectomy ; Humans ; Immunohistochemistry ; Intervertebral Disc Degeneration ; Intervertebral Disc* ; Nerve Endings ; Neurotransmitter Agents ; Pathology ; Scoliosis ; Substance P ; Total Disc Replacement