424 research outputs found

    Neurite Outgrowth Inhibitors in Gliotic Tissue

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    Robot therapy for functional recovery of the upper limbs: a pilot study on patients after stroke.

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    Objective: To verify the possibility of administering robotaided therapy for the upper limbs in patients after stroke; to evaluate patients' degree of acceptance and compliance with the treatment; to establish if the treatment has an effect on motor impairment and functional outcome. Design: Quasi-experimental, uncontrolled study. Subjects: Fourteen patients with chronic hemiparesis after stroke. Methods: Patients were treated with a robotic system for the upper limbs (ReoGo TM ; Motorika Medical Ltd, Israel). Subjects performed the following assessment, at the start (T0), at the end of treatment (T1), and at the follow-up performed one month after the end of treatment (T2): Fugl-Meyer test (FM) for upper limbs; strength evaluation; Ashworth scale; visual analogue scale (VAS) for pain; Frenchay Arm test (FAT); Box and Block test (BB Functional Independence Measure (FIM TM ); ABILHAND Questionnaire; Timed Up and Go test (TUG); Euro-Quality of Life questionnaire and; a VAS for treatment satisfaction were administered to the subjects. Results: Total scores of FM, B&B, FAT and FIM TM showed a statistically significant improvement from T0 and T1 (FM p < 0.002, B&B p < 0.012, FAT p < 0.023, FIM TM p < 0.007) and from T0 and T2 (FM p < 0.003, B&B p < 0.011, FAT p < 0.024, FIM p < 0.027). No statistically significant differences were found between evaluations at T1 and T2 (FM p < 0.595, B&B p < 0.491, FAT p < 0.317, FIM p < 0.180). Conclusion: The sample was capable of completing the treatment and demonstrated good participant satisfaction. This pilot study led to the finding of a clinical improvement and excellent patient compliance. It can be hypothesized that the results are robot-dependent and that they were learned and then maintained. However, the study is limited in that a control group was not used. As such, it is desirable to continue this study with a control group, as well as by designing a prospective longitudinal randomized controlled trial study

    A novel framework to study the impact of binding energy distributions on the chemistry of dust grains

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    The evaporation of molecules from dust grains is crucial to understand some key aspects of the star- and the planet-formation processes. During the warm-up phase the presence of young protostellar objects induces molecules to evaporate from the dust surface into the gas phase, enhancing its chemical complexity. Similarly, in circumstellar disks, the position of the so-called snow-lines is determined by evaporation, with important consequences for the formation of planets. The amount of molecules that are desorbed depends on the interaction between the species and the grain surface, which is controlled by the binding energy. Recent theoretical and experimental works point towards a distribution of values for this parameter instead of the single value often employed in astrochemical models.We present here a new "multi-binding energy" framework, to assess the effects that a distribution of binding energies has on the amount of species bound to the grains. We find that the efficiency of the surface chemistry is significantly influenced by this process with crucial consequences on the theoretical estimates of the desorbed species.Comment: Accepted A&

    Sonic hedgehog guides post-crossing commissural axons both directly and indirectly by regulating Wnt activity

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    After midline crossing, axons of dorsolateral commissural neurons turn rostrally into the longitudinal axis of the spinal cord. In mouse, the graded distribution of Wnt4 attracts post-crossing axons rostrally. In contrast, in the chicken embryo, the graded distribution of Sonic hedgehog (Shh) guides post-crossing axons by a repulsive mechanism mediated by hedgehog-interacting protein. Based on these observations, we tested for a possible cooperation between the two types of morphogens. Indeed, we found that Wnts also act as axon guidance cues in the chicken spinal cord. However, in contrast to the mouse, Wnt transcription did not differ along the anteroposterior axis of the spinal cord. Rather, Wnt function was regulated by a gradient of the Wnt antagonist Sfrp1 (Secreted frizzled-related protein 1) that in turn was shaped by the Shh gradient. Thus, Shh affects post-crossing axon guidance both directly and indirectly by regulating Wnt function

    Sfrp1 deficiency makes retinal photoreceptors prone to degeneration

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    Millions of individuals worldwide suffer from impaired vision, a condition with multiple origins that often impinge upon the light sensing cells of the retina, the photoreceptors, affecting their integrity. The molecular components contributing to this integrity are however not yet fully understood. Here we have asked whether Secreted Frizzled Related Protein 1 (SFRP1) may be one of such factors. SFRP1 has a context-dependent function as modulator of Wnt signalling or of the proteolytic activity of A Disintegrin And Metalloproteases (ADAM) 10, a main regulator of neural cell-cell communication. We report that in Sfrp1^{-/-} mice, the outer limiting membrane (OLM) is discontinuous and the photoreceptors disorganized and more prone to light-induced damage. Sfrp1 loss significantly enhances the effect of the Rpe6^{Leu450Leu} genetic variant -present in the mouse genetic background- which confers sensitivity to light-induced stress. These alterations worsen with age, affect visual function and are associated to an increased proteolysis of Protocadherin 21 (PCDH21), localized at the photoreceptor outer segment, and N-cadherin, an OLM component. We thus propose that SFRP1 contributes to photoreceptor fitness with a mechanism that involves the maintenance of OLM integrity. These conclusions are discussed in view of the broader implication of SFRP1 in neurodegeneration and aging

    Pαx6 Expression in Postmitotic Neurons Mediates the Growth of Axons in Response to SFRP1

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    During development, the mechanisms that specify neuronal subclasses are coupled to those that determine their axonal response to guidance cues. Pax6 is a homedomain transcription factor required for the specification of a variety of neural precursors. After cell cycle exit, Pax6 expression is often shut down in the precursor progeny and most postmitotic neurons no longer express detectable levels of the protein. There are however exceptions and high Pax6 protein levels are found, for example, in postmitotic retinal ganglion cells (RGCs), dopaminergic neurons of the olfactory bulb and the limbic system in the telencephalon. The function of Pax6 in these differentiating neurons remains mostly elusive. Here, we demonstrate that Pax6 mediates the response of growing axons to SFRP1, a secreted molecule expressed in several Pax6-positive forebrain territories. Forced expression of Pax6 in cultured postmitotic cortical neurons, which do not normally express Pax6, was sufficient to increment axonal length. Growth was blocked by the addition of anti-SFRP1 antibodies, whereas exogenously added SFRP1 increased axonal growth of Pax6-transfected neurons but not that of control or untransfected cortical neurons. In the reverse scenario, shRNA-mediated knock-down of Pax6 in mouse retinal explants specifically abolished RGCs axonal growth induced by SFRP1, but had no effect on RGCs differentiation and it did not modify the effect of Shh or Netrin on axon growth. Taken together these results demonstrate that expression of Pax6 is necessary and sufficient to render postmitotic neurons competent to respond to SFRP1. These results reveal a novel and unexpected function of Pax6 in postmitotic neurons and situate Pax6 and SFRP1 as pair regulators of axonal connectivity
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