Local vibration therapy promotes the recovery of nerve function in rats with sciatic nerve injury / 中西医结合学报

OBJECTIVE@#It has been reported that local vibration therapy can benefit recovery after peripheral nerve injury, but the optimized parameters and effective mechanism were unclear. In the present study, we investigated the effect of local vibration therapy of different amplitudes on the recovery of nerve function in rats with sciatic nerve injury (SNI).@*METHODS@#Adult male Sprague-Dawley rats were subjected to SNI and then randomly divided into 5 groups: sham group, SNI group, SNI + A-1 mm group, SNI + A-2 mm group, and SNI + A-4 mm group (A refers to the amplitude; n = 10 per group). Starting on the 7th day after model initiation, local vibration therapy was given for 21 consecutive days with a frequency of 10 Hz and an amplitude of 1, 2 or 4 mm for 5 min. The sciatic function index (SFI) was assessed before surgery and on the 7th, 14th, 21st and 28th days after surgery. Tissues were harvested on the 28th day after surgery for morphological, immunofluorescence and Western blot analysis.@*RESULTS@#Compared with the SNI group, on the 28th day after surgery, the SFIs of the treatment groups were increased; the difference in the SNI + A-2 mm group was the most obvious (95% confidence interval [CI]: [5.86, 27.09], P < 0.001), and the cross-sectional areas of myocytes in all of the treatment groups were improved. The G-ratios in the SNI + A-1 mm group and SNI + A-2 mm group were reduced significantly (95% CI: [-0.12, -0.02], P = 0.007; 95% CI: [-0.15, -0.06], P < 0.001). In addition, the expressions of S100 and nerve growth factor proteins in the treatment groups were increased; the phosphorylation expressions of ERK1/2 protein in the SNI + A-2 mm group and SNI + A-4 mm group were upregulated (95% CI: [0.03, 0.96], P = 0.038; 95% CI: [0.01, 0.94], P = 0.047, respectively), and the phosphorylation expression of Akt in the SNI + A-1 mm group was upregulated (95% CI: [0.11, 2.07], P = 0.031).@*CONCLUSION@#Local vibration therapy, especially with medium amplitude, was able to promote the recovery of nerve function in rats with SNI; this result was linked to the proliferation of Schwann cells and the activation of the ERK1/2 and Akt signaling pathways.

Effect of fasudil on experimental autoimmune neuritis and its mechanisms of action

This study aimed to investigate the therapeutic effect of fasudil on treating experimental autoimmune neuritis (EAN). Twenty-four EAN mice were randomly assigned to fasudil treatment (Fasudil group) or saline treatment (EAN model group) for 28 days. Clinical symptom score was evaluated every other day; inflammatory cell infiltration, demyelination, anti-myelin basic protein (MBP), inflammatory cytokines, inducible nitric oxide synthase (iNOS), and arginase-1 were detected in sciatic nerves at day 28. Th1, Th2, Th17, and Tregs proportions in splenocytes were detected at day 28. Clinical symptom score was found to be attenuated in the Fasudil group compared to the EAN model group from day 12 to day 28. Sciatic nerve inflammatory cell counts by HE staining and demyelination by luxol fast blue staining were both reduced, while MBP was increased in the Fasudil group compared to the EAN model group at day 28. Interferon γ (IFN-γ) and interleukin (IL)-17 were reduced, while IL-4 and IL-10 were elevated in the Fasudil group at day 28. Sciatic nerve M1 macrophages marker iNOS was decreased while M2 macrophages marker arginase-1 was increased in the Fasudil group at day 28. CD4+IFN-γ+ (Th1) and CD4+IL-17+ (Th17) cell proportions were both decreased, CD4+IL-4+ (Th2) cell proportion was similar, while CD25+FOXP3+ (Treg) cell proportion in splenocytes was increased in the Fasudil group. In summary, fasudil presented a good therapeutic effect for treating EAN by attenuating Th1/Th17 cells and promoting Tregs activation as well as M2 macrophages polarization.

Effect of Mycobacterium leprae on neurotrophins expression in human Schwann cells and mouse sciatic nerves

BACKGROUND Although Mycobacterium leprae (ML) is well characterised as the causative agent of leprosy, the pathophysiological mechanisms underlying peripheral nerve damage still need further understanding. In vitro and in vivo studies have yielded insights into molecular mechanisms of ML interaction with Schwann cells (SC), indicating the regulation of genes and proteins crucial to neural plasticity. OBJECTIVES We aimed to investigate the effect of ML on neurotrophins expression in human SC (hSC) and mice sciatic nerves to better understand their role in leprosy neuropathy, and aiming to contribute to future therapeutic approaches. METHODS We evaluated mRNA and protein expression of BDNF, NGF, NT-3, NT-4 in hSC from amputation nerve fragments, as well as in athymic nude mice, infected by ML for eight months. FINDINGS and MAIN CONCLUSIONS Our in vitro results showed a trend to decline in NGF and BDNF mRNA in ML-treated hSC, compared to controls. The immunodetection of BDNF and NT-4 was significantly downregulated in ML-treated hSC. Conversely, ML-infected mice demonstrated upregulation of NT-3, compared to non-infected animals. Our findings indicate that ML may be involved in neurotrophins regulation, suggesting that a pathogen-related imbalance of these growth factors may have a role in the neural impairment of leprosy.

Expression of myo-inositol cotransporters in the sciatic nerve and dorsal root ganglia in experimental diabetes

The transport of myo-inositol is the main mechanism for the maintenance of its high intracellular levels. We aimed to measure the mRNA and protein levels of myo-inositol cotransporters in the sciatic nerve (SN) and dorsal root ganglia (DRG) during experimental diabetes. Streptozotocin-induced (STZ; 4, 8, and 12 weeks; 65 mg/kg; ip) diabetic rats (DB) and age-matched euglycemic (E) rats were used for the analysis of mRNA and protein levels of sodium myo-inositol cotransporters 1, 2 (SMIT1, SMIT2) or H+/myo-inositol cotransporter (HMIT). There was a significant reduction in the mRNA levels for SMIT1 in the SN and DRG (by 36.9 and 31.0%) in the 4-week DB (DB4) group compared to the E group. SMIT2 was not expressed in SN. The mRNA level for SMIT2 was up-regulated only in the DRG in the DB4 group. On the other hand, the protein level of SMIT1 decreased by 42.5, 41.3, and 44.8% in the SN after 4, 8, and 12 weeks of diabetes, respectively. In addition, there was a decrease of 64.3 and 58.0% of HMIT in membrane and cytosolic fractions, respectively, in the SN of the DB4 group. In the DRG, there was an increase of 230 and 86.3% for SMIT1 and HMIT, respectively, in the DB12 group. The levels of the main inositol transporters, SMIT1 and HMIT, were greatly reduced in the SN but not in the DRG. SMIT-1 was selectively reduced in the sciatic nerve during experimental STZ-induced diabetes.

Transcriptomic differential lncRNA expression is involved in neuropathic pain in rat dorsal root ganglion after spared sciatic nerve injury

Dorsal root ganglia (DRG) neurons regenerate spontaneously after traumatic or surgical injury. Long noncoding RNAs (lncRNAs) are involved in various biological regulation processes. Conditions of lncRNAs in DRG neuron injury deserve to be further investigated. Transcriptomic analysis was performed by high-throughput Illumina HiSeq2500 sequencing to profile the differential genes in L4-L6 DRGs following rat sciatic nerve tying. A total of 1,228 genes were up-regulated and 1,415 down-regulated. By comparing to rat lncRNA database, 86 known and 26 novel lncRNA genes were found to be differential. The 86 known lncRNA genes modulated 866 target genes subject to gene ontology (GO) and KEGG enrichment analysis. The genes involved in the neurotransmitter status of neurons were downregulated and those involved in a neuronal regeneration were upregulated. Known lncRNA gene rno-Cntnap2 was downregulated. There were 13 credible GO terms for the rno-Cntnap2 gene, which had a putative function in cell component of voltage-gated potassium channel complex on the cell surface for neurites. In 26 novel lncRNA genes, 4 were related to 21 mRNA genes. A novel lncRNA gene AC111653.1 improved rno-Hypm synthesizing huntingtin during sciatic nerve regeneration. Real time qPCR results attested the down-regulation of rno-Cntnap lncRNA gene and the upregulation of AC111653.1 lncRNA gene. A total of 26 novel lncRNAs were found. Known lncRNA gene rno-Cntnap2 and novel lncRNA AC111653.1 were involved in neuropathic pain of DRGs after spared sciatic nerve injury. They contributed to peripheral nerve regeneration via the putative mechanisms.

Consumption and expenditure on food prepared away from home among Mexican adults in 2006 / Consumo y gasto en alimentos preparados fuera de casa en adultos mexicanos en 2006

Objective. To describe food expenditure and consumption of foods prepared away from home among Mexican adults. Materials and methods. Data were from 45 241 adult participants in the National Health and Nutrition Survey 2006, a nationally-representative, cross-sectional survey of Mexican households. Descriptive statistics and multivariable linear and logistic regression were used to assess the relationship between location of residence, educational attainment, socioeconomic status and the following: 1) expenditure on all food and at restaurants, and 2) frequency of consumption of comida corrida or restaurant food and street food. Results. Food expenditure and consumption of food prepared away from home were positively associated with socioeconomic status, educational attainment, and urban vs. rural residence (p<0.001 for all relationships in bivariate analyses). Conclusions. Consumption of food prepared outside home may be an important part of the diet among urban Mexican adults and those with high socioeconomic status and educational attainment.

Objetivo. Describir los gastos en alimentos y el consumo de alimentos preparados fuera de casa en población mexicana. Material y métodos. Los datos fueron de 45 241 adultos mexicanos en la Encuesta Nacional de Salud y Nutrición de 2006, representativa al nivel nacional. Se utilizaron estadísticas descriptivas y regresión linear y logística para estimar la relación entre el lugar de residencia, el nivel educativo y el nivel socioeconómico, con el gasto en todos los alimentos y en restaurantes, y con la frecuencia de consumo de comida corrida, en restaurantes y de la calle. Resultados. El gasto en alimentos y el consumo de alimentos preparados se asociaron positivamente con el nivel socioeconómico, el nivel educativo y la residencia rural (p<0,001 para todas las relaciones). Conclusiones. El consumo de alimentos preparados puede ser una parte importante de la dieta de los adultos urbanos y de aquéllos con altos niveles socioeconómicos y educativos.

S100ß and fibroblast growth factor-2 are present in cultured Schwann cells and may exert paracrine actions on the peripheral nerve injury / S100ß e fator de crescimento de fibroblasto-2 estão presentes nas células de Schwann cultivadas e exercem ações parácrinas na lesão do nervo

PURPOSE: The neurotrophic factor fibroblast growth factor-2 (FGF-2, bFGF) and Ca++ binding protein S100ß are expressed by the Schwann cells of the peripheral nerves and by the satellite cells of the dorsal root ganglia (DRG). Recent studies have pointed out the importance of the molecules in the paracrine mechanisms related to neuronal maintenance and plasticity of lesioned motor and sensory peripheral neurons. Moreover, cultured Schwann cells have been employed experimentally in the treatment of central nervous system lesions, in special the spinal cord injury, a procedure that triggers an enhanced sensorymotor function. Those cells have been proposed to repair long gap nerve injury. METHODS: Here we used double labeling immunohistochemistry and Western blot to better characterize in vitro and in vivo the presence of the proteins in the Schwann cells and in the satellite cells of the DRG as well as their regulation in those cells after a crush of the rat sciatic nerve. RESULTS: FGF-2 and S100ß are present in the Schwann cells of the sciatic nerve and in the satellite cells of the DRG. S100ß positive satellite cells showed increased size of the axotomized DRG and possessed elevated amount of FGF-2 immunoreactivity. Reactive satellite cells with increased FGF-2 labeling formed a ring-like structure surrounding DRG neuronal cell bodies.Reactive S100ß positive Schwann cells of proximal stump of axotomized sciatic nerve also expressed higher amounts of FGF-2. CONCLUSION: Reactive peripheral glial cells synthesizing FGF-2 and S100ß may be important in wound repair and restorative events in the lesioned peripheral nerves.

OBJETIVO: O fator neurotrófico fator de crescimento de fibroblastos-2 (FGF-2, bFGF) e a proteína ligante de Ca++ S100ß são expressos pelas células de Schwann dos nervos e por células satélites do gânglio da raiz dorsal (GRD). Estudos recentes indicam a importância das moléculas nos mecanismos parácrinos relacionados à manutenção neuronal e à plasticidade de neurônios periféricos motores e sensoriais. Além disso, células de Schwann cultivadas têm sido empregadas experimentalmente no tratamento de lesões no sistema nervo central, especialmente na lesão da medula espinal, a qual mostrou uma melhora da função sensoriomotora. Estas células são ainda propostas no reparo do nervo lesado com perda de tecido. MÉTODOS: Usamos a dupla marcação imunohistoquímica e o Western blot para caracterizar melhor in vitro e in vivo a presença das proteínas nas células de Schwann e nas células satélites do GRD assim como sua regulação nessas células após a compressão do nervo ciático de ratos. RESULTADOS: FGF-2 e S100ß estão presentes nas células de Schwann do nervo ciático e nas células satélites do GRD. Células satélites do GRD axotomizado positivas para S100ß possuíam quantidade aumentada de imurreatividade da FGF-2. Células satélites reativas apresentando maior quantidade de FGF-2 formaram um anel ao redor dos corpos neuronais do GRD. Células de Schwann do coto proximal à axotomia do nervo ciático e positivas para S100ß também expressaram quantidades aumentadas de FGF-2. CONCLUSÃO: As células gliais periféricas ao sintetizar FGF-2 e S100ß podem ser importantes no reparo de cicatrização e em eventos restaurativos nas lesões do nervo.

Effect of FK506 on expression of hepatocyte growth factor in murine spinal cord following peripheral nerve injury / 华中科技大学学报（医学）（英德文版）

This study is to investigate the effect of FK506 on expression of hepatocyte growth factor (HGF) in rats' spinal cord following peripheral nerve injury and to elucidate the mechanisms for neuroprotective property of FK506. Fifty male rats were randomly divided into normal group, injury group and treatment group. Models of peripheral nerve injury were established by bilateral transection of sciatic nerve 0.5 cm distal to piriform muscle. Then the treatment group received subcutaneous injection of FK506 (1 mg/kg) at the back of neck, while the injury group was given 0.9% saline. The L(4-6) spinal cords were harvested at various time points after the surgery. Western blotting and immunofluorescent staining were used to detect the level and position of HGF in spinal cord. Immunofluorescent staining showed that HGF-positive neurons were located in anterior horn, intermediate zone and posterior horn of gray matter in normal spinal cord. Western blotting revealed that there was no significant difference in the expressions of HGF between the injury group and the normal group, while the expression of HGF was significantly higher in the treatment group than in the injury group 7 and 14 days after surgery. It is suggested that peripheral nerve injury does not result in up-regulation of the expression of HGF in spinal cord, while FK506 may induce high expression of endogenous HGF after injury thereby protecting neurons and promoting axonal outgrowth.

Efeito analgésico de longa duração da dipirona sobre a hiperalgesia persistente induzida pela constrição do nervo ciático em ratos: participação do óxido nítrico / Long term analgesic effect of dipyrone on the persistent hyperalgesia induced by chronic constriction injury of sciatic nerve in rats: involviment of nitric oxide

O efeito analgésico de longa duração da dipirona foi avaliado em um modelo de dor neuropática assim como a participação da via óxido nítrico-GMPc neste mecanismo analgésico. Uma única administração intraplantar de dipirona (80 æg), no 14° dia após a instalação da hiperalgesia neuropática induzida pela constrição do nervo ciático exerceu um efeito analgésico, significativo e de longa duração. A inibição da óxido nítrico sintetase com L-NAME (50 ou 100 æg/pata), ou do óxido nítrico (NO) endógeno com hemoglobina (10 ou 30 æg/pata), bloquearam o desenvolvimento do efeito analgésico da dipirona. A L-arginina (500 æg/pata) reverteu o efeito do L-NAME. Cloreto de metiltionínio (azul de metileno) (500 æg/pata), ODQ (50 æg/pata) (bloqueadores da guanilil ciclase) ou glibenclamida (100, 200 ou 300 æg/pata) (bloqueador de canais de K+ sensíveis ao ATP) inibiram o efeito analgésico da dipirona. O nitroprussiato de sódio administrado no 14° dia após a instalação da hiperalgesia neuropática também exerceu efeito analgésico de longa duração, semelhante ao observado com a dipirona. Sugerimos que a ação analgésica periférica e de longa duração da dipirona, neste modelo experimental, ocorra devido a provável dessensibilização dos nociceptores, envolvendo a via óxido nítrico - GMPc e canais de K+ sensíveis ao ATP.

The long term analgesic effect of dipyrone was evaluated on a model of neuropathic pain and the role of nitric oxide/GMPc pathway in this antinociceptive mechanism. One intraplantar dipyrone administration (80 mg), at 14th day after the chronic constriction injury of the sciatic nerve, induced a significant and long term analgesic effect. The inhibition of nitric oxide synthase (NOS) with L-NAME (50 or 100 mg/paw) or scavenging of the endogenous NO with hemoglobin (10 or 30 mg/paw) inhibited the development of the dipyrone analgesia. L-arginine (500 mg/paw) could reverted the effect of L-NAME. Metylene blue (500 mg/paw) or ODQ (50 mg/paw) (blockers of guanyl cyclase), or glybenclamide (100, 200 or 300 mg/paw) (blocker of ATP-sensitive K+ channels) inhibited the development of dipyrone analgesia. The sodium nitroprussiate administered at 14th day after the chronic constriction injury of the sciatic nerve also induced a long term analgesic effect similar to that of dipyrone. Our data may support the suggestion that the peripheral and the long term analgesic action of dipyrone on this model experimental occurs due to a probable nociceptor desensitisation with involviment of activation of the nitric oxide-cGMP pathway, followed by an opening of ATP-sensitive K+ channels.

Ca2+ -free medium enhances the magnitude of slow peak in compound action potential of frog sciatic nerve in vitro.

The present investigation was carried out to know the effect of Ca2+ on different peaks of compound action potential (CAP) representing the fibers having different conduction velocity. CAP was recorded from a thin bundle of nerve fibers obtained from desheathed frog sciatic nerve. Suction electrodes were used for stimulating and recording purposes. In Ca2+ -free amphibian Ringer, two distinct peaks (Peak-I and Peak-II) were observed. The threshold, conduction velocity (CV), amplitude and duration of Peak-I were 0.32 +/- 0.02 V, 56 +/- 3.0 m/sec, 2.1 +/- 0.2 mV and 0.75 +/- 0.1 ms, respectively. The Peak-II exhibited ten times greater threshold, eight times slower CV, three times lower amplitude and four times greater duration as compared to Peak-I. Addition of 2 mM Ca2+ in the bathing medium did not alter CAP parameters of Peak-I excepting 25% reduction in CV. But, in Peak-II there was 70-75% reduction in area and amplitude. The concentration-attenuation relation of Peak-II to various concentrations of Ca2+ was nonlinear and 50% depression occurred at 0.35 mM of Ca2+. Washing with Ca2+ -free solution with or without Mg2+ (2 mM)/verapamil (10 microM) could not reverse the Ca2+ -induced changes in Peak-II. Washing with Ca2+ -free solution containing EDTA restored 70% of the response. The results indicate that Ca2+ differentially influence fast and slow conducting fibers as the activity of slow conducting fibers is greatly suppressed by external calcium.

Increased expression of osteopontin in the spinal cords of Lewis rats with experimental autoimmune neuritis

To investigate the pattern of expression of osteopontin (OPN) in tissues of the central nervous system (CNS) responding to peripheral immunological stimulation, the expression of OPN was studied in the spinal cord of rats with experimental autoimmune neuritis (EAN). In this model system, the sciatic nerves and spinal nerve roots are the target organs of EAN and the spinal cord is a remote organ that may be indirectly affected. OPN was constitutively expressed in some astrocytes adjacent to the pia mater and neurons in normal rats. In rats with EAN, OPN was increased in the same cells and in some inflammatory cells, including macrophages in the subarachnoid space. Expression of CD44, a receptor of OPN, was weak in normal spinal cord tissue and increased in the entire spinal cord parenchyma in rats with EAN, as well as in inflammatory cells. These findings suggest that inflammatory cells as well as reactive astrocytes are major sources of OPN and CD44 in the spinal cord of rats with EAN. Further study is needed to elucidate the functional role of OPN in the spinal cord affected by EAN.

Expression of PSD95 in the Rat Sciatic Nerve

This study was designed to elucidate the existence of PSD95 in the rat sciatic nerve. Immunohistochemical stains of cryosection and teased fiber of sciatic nerves were performed with goat polyclonal antibody against PSD95. Western blot analysis was also accomplished with the same antibody. We got an interesting result that the rat sciatic nerve obviously showed PSD95 immunoreactivity especially in the nodal and paranodal regions, and we also identified a distinct band of PSD95 by western blot. These results suggest PSD95 exists in the sciatic nerve as well as it does in the central nervous system. We suppose PSD95 may have some important roles in ion channel clustering, junctional plasticity and signal transduction in the peripheral nerves as well.

Hernia de disco lumbosacra en niños y adolescentes

A pesar de ser una patología frecuente en adultos (30 por ciento), la incidencia en niños es de solo 0,5 a 5 por ciento. Se deben a la protrusión del núcleo pulposo del disco intervertebral a través del anillo del mismo disco y se cree que en personas jóvenes se debe a continuos traumatismos o esfuerzos físicos y el antecedente de trauma agudo se considera como el desencadenante del cuadro clínico. Se ha propuesto incluso el factor genético. La sintomatología se produce por compresión o irritación del nervio ciático, médula espinal o cola de caballo. El diagnóstico se establece con el cuadro clínico que se presenta con lumbalgia o ciatalgia, escoliosis antálgica, signos de Lasegue y Bragard positivos, y se confirma y establece la etiología de los mismos con la ayuda de Rx, TAC, RMN y radiculografía. Actualmente se prefiere el tratamiento conservador basado en reposo, ejercicios dirigidos, órtesis y medicación; el tratamiento quirúrgico está limitado a escasos pacientes y dependiendo del tipo de hernia se usara algunas técnicas.