Expression of CCR2 in both resident and bone marrow-derived microglia plays a critical role in neuropathic pain

La douleur neuropathique suite à une lésion d'un nerf périphérique est une condition répandue pour laquelle aucun traitement efficace n'est disponible. Sans nier le rôle joué par les neurones au niveau du système nerveux central (SNC), des données récentes ont démontré la participation active des cellules gliales dans le développement de la douleur neuropathique. En effet, des études ont montré un rôle critique des cellules gliales dans l'initiation et la maintenance de l'hypersensibilité liée à la douleur. Cependant, les origines de ces cellules gliales activées et les déclencheurs de leur activation n'ont pas encore été élucidés. Nous avons démontré dans cette étude que suite à une blessure au nerf périphérique, causée par la ligation partielle du nerf sciatique, en plus des l'activation de microglies résidentes du SNC, les cellules hématogènes, macrophages/monocytes, infiltrent la moelle épiniere, prolifèrent et se différencient en microglies ramifiées. La signalisation entre la chimiokine "monocyte chemoattractant protein-1" (MCP-1, CCL2) et son récepteur CCR2 est critique dans l'activation des cellules microglials de la moelle épiniere. En effet, l'injection intrathécale de MCP-1 exogène entraine l'activation des microglies chez des souris sauvages, mais pas chez des souris déficientes en CCR2. De plus, un traitement avec un anticorps neutralisant dirigé contre MCP-1 a empêché l'infiltration de cellules microglials dérivées de la moelle osseuse (MDMO) dans la moelle épiniere après le dommage du nerf sciatique. En utilisant les souris CCR2 knock-out-sélectif dans la microglie résidente ou la MDMO, nous avons constaté que, bien que des souris CCR2 knock-out-total n'ont pas développé l'activation microgliale ni l'allodynie mécanique, l'expression de CCR2 soit dans les microglies résidentes ou dans les MDMO est suffisante pour le développement d'allodynie mécanique. Ainsi, pour soulager de façon efficace la douleur neuropathique, il faut viser non seulement la microglie résidente du SNC, mais aussi la microglie provenant de la circulation sanguine. Ces découvertes ouvrent la porte pour une nouvelle stratégie thérapeutique: on peut profiter de la capacité naturelle des cellules dérivées de la moelle osseuse qui s'infiltrent sélectivement des régions affectées du SNC en utilisant ces cellules comme le véhicule pour la livraison de médicaments afin de contrôler l'hypersensibilité et la douleur chronique

Dynamics of quantum entanglement in the reservoir with memory effects

The non-Markovian dynamics of quantum entanglement is studied by the Shabani-Lidar master equation when one of entangled quantum systems is coupled to a local reservoir with memory effects. The completely positive reduced dynamical map can be constructed in the Kraus representation. Quantum entanglement decays more slowly in the non-Markovian environment. The decoherence time for quantum entanglement can be markedly increased by the change of the memory kernel. It is found out that the entanglement sudden death between quantum systems and entanglement sudden birth between the system and reservoir occur at different instants.Comment: 14 pages, 3 figure

A new animal model of spontaneous autoimmune peripheral polyneuropathy: implications for Guillain-Barré syndrome

BACKGROUND: Spontaneous autoimmune peripheral neuropathy including Guillain-Barré Syndrome (GBS) represents as one of the serious emergencies in neurology. Although pathological changes have been well documented, molecular and cellular mechanisms of GBS are still under-explored, partially due to short of appropriate animal models. The field lacks of spontaneous and translatable models for mechanistic investigations. As GBS is preceded often by viral or bacterial infection, a condition can enhance co-stimulatory activity; we sought to investigate the critical role of T cell co-stimulation in this autoimmune disease. RESULTS: Our previous study reported that transgene-derived constitutive expression of co-stimulator B7.2 on antigen presenting cells of the nervous tissues drove spontaneous neurological disorders. Depletion of CD4(+) T cells in L31 mice accelerated the onset and increased the prevalence of the disease. In the current study, we further demonstrated that L31/CD4(-/-) mice exhibited both motor and sensory deficits, including weakness and paresis of limbs, numbness to mechanical stimuli and hypersensitivity to thermal stimulation. Pathological changes were characterized by massive infiltration of macrophages and CD8(+) T cells, demyelination and axonal damage in peripheral nerves, while changes in spinal cords could be secondary to the PNS damage. In symptomatic L31/CD4(-/-) mice, the disruption of the blood neural barriers was observed mainly in peripheral nerves. Interestingly, the infiltration of immune cells was initiated in pre-symptomatic L31/CD4(-/-) mice, prior to the disease onset, in the DRG and spinal roots where the blood nerve barrier is virtually absent. CONCLUSIONS: L31/CD4(-/-) mice mimic most parts of clinical and pathological signatures of GBS in human; thus providing an unconventional opportunity to experimentally explore the critical events that lead to spontaneous, autoimmune demyelinating disease of the peripheral nervous system

Residual Stress Analysis of Laser Remanufacturing

Laser remanufacturing is an advanced repairing method to remanufacture damaged parts based on laser processing, such as laser cladding and laser welding. As a critical factor in determining the remanufacturing quality, residual stress of different laser-remanufactured parts was analysed by numerical methods based on deactivating and reactivating element theory, as well as experimental methods such as X-ray diffraction and hole drilling measurements. The distributions and evolution law of residual stress during multipass laser welding of 7A52 high-strength aluminium alloy, and the effects of forming strategy, heat input and solid-state phase transition on residual stress in the laser cladding forming layers of QT 500 cast iron and FV520B high strength steel, were emphatically studied. The simulation results of residual stress fit well with the experimental results, indicating that both residual stress and its accumulation phenomenon would occur during the laser welding and laser cladding forming, and were affected by factors such as welding pass, heat input and phase transition. It is feasible to control residual stress by using cross path forming strategy, less heat input and alloying power materials with low martensite transition point (Ms)

Comparative analysis of different cyclosporine A doses on protection after myocardial ischemia/reperfusion injury in rat

AbstractObjectiveTo investigate the protective effect of different cyclosporin A (CsA) doses on myocardial ischemia/reperfusion injury in rat models.MethodsA rat model of myocardial ischemia/reperfusion injury was established in vivo and the rats were randomly divided into four groups: placebo (PBS; T1), low-dose (CsA dose: 1.0 mg/kg; T2), medium-dose (CsA dose: 2.5 mg/kg; T3), and high-dose (CsA dose: 5.0 mg/kg; T4) groups. Heart function indexes were monitored at different time points, the extent of myocardial infarction was assessed by Evans Blue-TTC staining, and creatine kinase MB mass and cardiac troponin I values were measured by biochemical assays.ResultsCompared with the T1 and T2 groups, both the creatine kinase MB mass and cardiac troponin I were significantly lower in the T3 and T4 groups (P<0.05). The mean arterial pressure (MAP) and left ventricular systolic pressure (LVSP) decreased sequentially in each group, with the extending reperfusion time. Significant decreases in LVSP and MAP were observed in the T3 and T4 groups as compared to the T1 and T2 group (P<0.05), and the T2 group showed a significantly lower LVSP and MAP decline than the T1 group (P<0.05). Compared with the T1 group, the rats from the T2, T3, and T4 groups suffered from a significantly lower extent of myocardial infarction (P<0.05). Also, the animals in the T3 and T4 groups had a significantly smaller extent of myocardial infarction than those in the T2 group (P<0.05).ConclusionsVarious CsA doses exert different degrees of protection against ischemia/reperfusion injury, and this protective effect peaks at approximately 2.5 mg/kg in rat models

Isopropyl 3,4-dihy­droxy­benzoate

In the crystal structure of the title compound, C10H12O4, O—H⋯O hydrogen bonds incorporating R 2 2(10) and R 2 2(14) motifs link mol­ecules into chains along [10]. An intra­molecular O—H⋯O hydrogen bond is also observed

Human Gingiva-Derived Mesenchymal Stem Cells Elicit Polarization of M2 Macrophages and Enhance Cutaneous Wound Healing

Increasing evidence has supported the important role of mesenchymal stem cells (MSCs) in wound healing, however, the underlying mechanism remains unclear. Recently, we have isolated a unique population of MSCs from human gingiva (GMSCs) with similar stem cell-like properties, immunosuppressive, and anti-inflammatory functions as human bone marrow-derived MSCs (BMSCs). We describe here the interplay between GMSCs and macrophages and the potential relevance in skin wound healing. When cocultured with GMSCs, macrophages acquired an anti-inflammatory M2 phenotype characterized by an increased expression of mannose receptor (MR; CD206) and secretory cytokines interleukin (IL)-10 and IL-6, a suppressed production of tumor necrosis factor (TNF)-α, and decreased ability to induce Th-17 cell expansion. In vivo, we demonstrated that systemically infused GMSCs could home to the wound site in a tight spatial interaction with host macrophages, promoted them toward M2 polarization, and significantly enhanced wound repair. Mechanistically, GMSC treatment mitigated local inflammation mediated by a suppressed infiltration of inflammatory cells and production of IL-6 and TNF-α, and an increased expression of IL-10. The GMSC-induced suppression of TNF-α secretion by macrophages appears to correlate with impaired activation of NFκB p50. These findings provide first evidence that GMSCs are capable to elicit M2 polarization of macrophages, which might contribute to a marked acceleration of wound healing. © AlphaMed Press

Effect of Atractylodes macrocephala extract on chronic heart failure in rats

Purpose: To investigate the effect of Atractylodes macrocephala extract (AME) on oxidative stress and hemodynamics in chronic congestive heart failure (CHF) rats. Methods: After Sprague Dawley (SD) rats were successfully establised into CHF, they were randomly divided into normal control group, negative control group, captopril group, as well as 1.4, 2.8 and 5.6 g/kg of AME groups, and treated with drugs for 4 weeks. Hemodynamic function, whole heart weight index, blood creatinine kinase (CK), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), nitric oxide synthase (NOS) were measured. Results: Compared with the normal control group, arterial systolic pressure (SBP)(83.12 ± 16.21 mmHg), diastolic pressure (DBP, (75.16 ± 20.18 mmHg), mean arterial pressure (MAP 76.32 ± 13.43 mmHg), heart rate (HR 353.25 ± 36.34 beats/min), left ventricular systolic peak (LVSP 101.24 ± 16.13 mmHg), and left ventricular pressure change rate (dp/dt max) significantly decreased (p &lt; 0.05), while left ventricular end diastolic pressure (LVEDP (22.13 ± 1.57 mmHg), whole heart weight index (2.74 ± 0.16 mg/g), blood CK (0.93 ± 0.14 U/mL), MDA (19.13 ± 2.26 nmol/mL), NO (34.21 ± 3.16 umol/L), and NOS (42.13 ± 3.24 U/mL) increased significantly increased in the negative control group (p &lt; 0.05). High dose AME significantly improved hemodynamic function, lowered MDA (8.75 ± 2.09 nmol/mL) and NO (22.14 ± 3.27 umol/L) levels (p &lt; 0.05), and also decreased CK (0.57 ± 0.31 U/mL) and NOS (24.24 ± 3.38 U/mL) in CHF rats (p &lt; 0.05). Conclusion: AME significantly improve adriamycin-induced chronic congestive heart failure in rats, which could be used for the therapeutic management of chronic congestive heart failure in future