Nerve growth factor: basic findings and clinical trials

The nerve growth factor is the first-discovered and best-characterized member of the family of neurotrophins. In the introduction of this article we present a brief biographic view of past and present studies of Rita Levi-Montalcini on nerve growth factor: Further, the article focuses on pleiotropic activities of nerve growth factor, exerting on various cell types, including cells of nervous, immune and endocrine system. Implications of these actions of nerve growth factor in the pathogenesis of neurological diseases, autoimmune-inflammatory diseases, allergic diseases, lymphoproliferative diseases, atherosclerotic cardiovascular disease, and neurotrophic corneal ulcers are outlined.Biomedical Reviews 1999; 10: 3-14

Quantitative Kinematic Characterization of Reaching Impairments in Mice After a Stroke

Background and Objective. Kinematic analysis of reaching movements is increasingly used to evaluate upper extremity function after cerebrovascular insults in humans and has also been applied to rodent models. Such analyses can require time-consuming frame-by-frame inspections and are affected by the experimenter's bias. In this study, we introduce a semi-automated algorithm for tracking forepaw movements in mice. This methodology allows us to calculate several kinematic measures for the quantitative assessment of performance in a skilled reaching task before and after a focal cortical stroke. Methods. Mice were trained to reach for food pellets with their preferred paw until asymptotic performance was achieved. Photothrombosis was then applied to induce a focal ischemic injury in the motor cortex, contralateral to the trained limb. Mice were tested again once a week for 30 days. A high frame rate camera was used to record the movements of the paw, which was painted with a nontoxic dye. An algorithm was then applied off-line to track the trajectories and to compute kinematic measures for motor performance evaluation. Results. The tracking algorithm proved to be fast, accurate, and robust. A number of kinematic measures were identified as sensitive indicators of poststroke modifications. Based on end-point measures, ischemic mice appeared to improve their motor performance after 2 weeks. However, kinematic analysis revealed the persistence of specific trajectory adjustments up to 30 days poststroke, indicating the use of compensatory strategies. Conclusions. These results support the use of kinematic analysis in mice as a tool for both detection of poststroke functional impairments and tracking of motor improvements following rehabilitation. Similar studies could be performed in parallel with human studies to exploit the translational value of this skilled reaching analysis

Interactions between self penetrating neural interfaces and peripheral nerves

This work provides a simple framework to optimize the design of self penetrating neural interfaces. First, an assessment of interactions between electrodes and peripheral nerves is provided and related to the instantaneous elasticity of the tissue. Then, the elastic instability of electrodes is considered, because it is the main cause of failure of implants. The connection between the previous two sections, integrated with an assessment of a safety coefficient for in-vivo implants, allows to predict some important parameters of a reliable electrode: its maximum slenderness ratio (SR) and the minimum Young modulus of its main shaft

A machine learning framework to optimize optic nerve electrical stimulation for vision restoration

Optic nerve electrical stimulation is a promising technique to restore vision in blind subjects. Machine learning methods can be used to select effective stimulation protocols, but they require a model of the stimulated system to generate enough training data. Here, we use a convolutional neural network (CNN) as a model of the ventral visual stream. A genetic algorithm drives the activation of the units in a layer of the CNN representing a cortical region toward a desired pattern, by refining the activation imposed at a layer representing the optic nerve. To simulate the pattern of activation elicited by the sites of an electrode array, a simple point-source model was introduced and its optimization process was investigated for static and dynamic scenes. Psychophysical data confirm that our stimulation evolution framework produces results compatible with natural vision. Machine learning approaches could become a very powerful tool to optimize and personalize neuroprosthetic systems

External sensory-motor cues while managing unexpected slippages can violate the planar covariation law.

This study was aimed at investigating the intersegmental coordination of six older adults while managing unexpected slippages delivered during steady walking, and wearing an Active Pelvis Orthosis (APO). The APO was setup either to assist volunteers at the hip levels during balance loss or to be transparent. The Planar Covariation Law (PCL) of the lower limb elevation angles was the main tool used to assess the intersegmental coordination of both limbs (i.e., the perturbed and unperturbed ones). Results revealed that, after the onset of the perturbation, elevation angles of both limbs do not covary, a part from the robot-mediated assistance. These new evidences suggest that external sensory-motor cues can alter the temporal synchronization of elevation angles, thus violating the PCL. (C) 2019 Elsevier Ltd. All rights reserved

NGF modulates trkANGFR/p75NTR in αsMA-expressing conjunctival fibroblasts from human ocular cicatricial pemphigoid (OCP)

OBJECTIVE: In a previous study, we reported the upregulation of Nerve Growth Factor (NGF) and trkANGFR expression in Ocular Cicatricial Pemphigoid (OCP), an inflammatory and remodeling eye disease. Herein, we hypothesize a potential NGF-driven mechanism on fibroblasts (FBs) during OCP remodeling events. To verify, human derived OCP-FBs were isolated and characterized either at baseline or after NGF exposure. MATERIALS AND METHODS: Conjunctival biopsies were obtained from 7 patients having OCP and 6 control subjects (cataract surgery). Both conjunctivas and primary FB cultures were characterised for αSMA, NGF and trkANGFR/p75NTR expression. Subcultures were exposed to NGF and evaluated for αSMA, NGF, trkANGFR/p75NTR expression as well as TGFβ1/IL4 release. For analysis, early and advanced subgroups were defined according to clinical parameters. RESULTS: OCP-conjunctivas showed αSMA-expressing FBs and high NGF levels. Advanced OCP-FBs showed higher αSMA expression associated with higher p75NTR and lower trkANGFR expression, as compared to early counterparts. αSMA expression was in keeping with disease severity and correlated to p75NTR. NGF exposure did not affect trkANGFR levels in early OCP-FBs while decreased both αSMA/p75NTR expression and TGFβ1/IL4 release. These effects were not observed in advanced OCP-FBs. CONCLUSIONS: Taken together, these data are suggestive for a NGF/p75NTR task in the potential modulation of OCP fibrosis and encourages further studies to fully understand the underlying mechanism occurring in fibrosis. NGF/p75NTR might be viewed as a potential therapeutic target

European study of research and development in mobility technology for persons with disabilities

In the fall of 2010, the National Science Foundation, the National Institutes of Health and the U.S. Veteran's Administration jointly supported a review of mobility technology in Europe. A delegation of American Scientists traveled to Europe to visit a number of research centers and engaged in a demonstration and dialogue related to the global state-of-the-art for mobility impairment rectification and augmentation. From the observations and exchanges between the U.S. delegation and host institutions, the researchers were able to derive a series of papers which are now published in this thematic series of Journal of NeuroEngineering and Rehabilitation. The papers describe the main themes of the European mobility technology research activities showing a healthy picture of research and innovation in the field

Soft Embodiment for Engineering Artificial Limbs

We highlight two alternative, yet complementary, solutions for harnessing available neural resources for improving integration of artificial limbs (ALs) through embodiment. ‘Hard’ embodiment exploits neural and cognitive body mechanisms by closely mimicking their original biological functions. ‘Soft’ embodiment exploits these same mechanisms by recycling them to support a different function altogether

Polysaccharide Layer-by-Layer Coating for Polyimide-Based Neural Interfaces

Implantable flexible neural interfaces (IfNIs) are capable of directly modulating signals of the central and peripheral nervous system by stimulating or recording the action potential. Despite outstanding results in acute experiments on animals and humans, their long-term biocompatibility is hampered by the effects of foreign body reactions that worsen electrical performance and cause tissue damage. We report on the fabrication of a polysaccharide nanostructured thin film as a coating of polyimide (PI)-based IfNIs. The layer-by-layer technique was used to coat the PI surface due to its versatility and ease of manufacturing. Two different LbL deposition techniques were tested and compared: dip coating and spin coating. Morphological and physiochemical characterization showed the presence of a very smooth and nanostructured thin film coating on the PI surface that remarkably enhanced surface hydrophilicity with respect to the bare PI surface for both the deposition techniques. However, spin coating offered more control over the fabrication properties, with the possibility to tune the coating’s physiochemical and morphological properties. Overall, the proposed coating strategies allowed the deposition of a biocompatible nanostructured film onto the PI surface and could represent a valid tool to enhance long-term IfNI biocompatibility by improving tissue/electrode integration