Functional and structural plasticity following action observation training in multiple sclerosis.

BACKGROUND: Hand motor deficits contribute to multiple sclerosis (MS)-related disability. Action observation training (AOT) is promising to improve upper limb function in neurologic patients. OBJECTIVES: In this preliminary study, we investigated AOT effects on dominant-hand motor performance in MS patients with upper limb motor impairment and performed an explorative analysis of their anatomical and functional magnetic resonance imaging (MRI) substrates. METHODS: In total, 46 healthy controls (HC) and 41 MS patients with dominant-hand motor impairment were randomized to AOT (HC-AOT = 23; MS-AOT = 20; watching daily-life action videos and execution) or control-training (HC-Control = 23; MS-Control = 21; watching landscapes videos and execution). Behavioral, structural, and functional (at rest and during object manipulation) MRI scans were acquired before and after a 2-week training. RESULTS: After training, MS groups improved in right upper limb functions, mainly in AOT group (p from 0.02 to 0.0001). All groups showed regional increased and decreased gray matter volume, with specific AOT effects in fronto-temporal areas in MS-AOT (p < 0.001), without white matter (WM) integrity modifications. Increased and reduced recruitments of the action observation matching system and its connections in MS-AOT were found (p < 0.001). Motor improvements were correlated with volumetric and functional MRI modifications (r from -0.78 to 0.77, p < 0.001). CONCLUSION: The 10-day AOT promotes clinical improvements in MS patients through structural and functional modifications of the action observation matching system.

Hepatitis C virus-related cryoglobulinemic vasculitis.

INTRODUCTION: Hepatitis C virus (HCV) infection affects about 170 million people worldwide. HCV is responsible for both hepatitis and extra-hepatic manifestations. Chronic infection has been shown to develop in about 70% of cases, and it can progress to cirrhosis or hepatocellular carcinoma. Ten percent of HCV patients may develop extra-hepatic manifestations, including mixed cryoglobulinemia (MC) and non-Hodgkin lymphomas (NHL). Cryoglobulinemic vasculitis (CV) varies, ranging from mild-moderate clinical symptoms (purpura on the legs, asthenia and arthralgias) and chronic hepatitis to severe symptoms (ulcers on the legs, peripheral neuropathy, glomerulonephritis, low-grade NHL to life threatening complications (rapid progressive glomerulonephritis, gastrointestinal vasculitis, acute hyper-viscosity). EVIDENCE ACQUISITION: CV is associated with significant morbidity and mortality. Some studies have shown kidney involvement, cirrhosis, central nervous system involvement, and heart involvement as unfavorable prognostic factors. Many studies have demonstrated that, after antiviral therapy, CV can disappear along with HCV. After the introduction of the new direct antiviral agents (DAAs), the combination of pegylated interferon and ribavirin has been abandoned. EVIDENCE SYNTHESIS: Several studies on new DAAs have reported remarkable 90% to 100% HCV eradication rates, regardless of genotype. Treatment with DAAs has comparable efficacy on viral eradication in CV patients but definite clinical improvements of vasculitis can be observed only in half the patients. CONCLUSIONS: In patients with mild to moderate CV disease, DAAs therapy should be used as first line approach. In patients with severe vasculitis, DAAs therapy and a second-line treatment with RTX with or without aphaeresis are a required.

The effect of action observation/execution on mirror neuron system recruitment: an fMRI study in healthy individuals.

Action observation and execution activate regions that are part of the motor and mirror neuron systems (MNS). Using functional magnetic resonance (fMRI), we defined the presence and extent of MNS activation during three different motor tasks with the dominant, right-upper limb in healthy individuals. The influence of the modality of task administration (execution, observation, observation and execution) was also investigated. fMRI scans during the execution (E) of a motor task, the observation (O) of a video showing the same task performed by another person and the simultaneous observation and execution (OE) of the task were obtained from three groups of healthy subjects (15 subjects per group) randomized to perform: a simple motor (SM) task, a complex motor (CM) task and a finalistic motor (FM) task. Manual dexterity was assessed using the 9-hole peg test and maximum finger tapping frequency. MNS activation was higher during FM than SM or CM tasks, independently from the modality of administration (E, O, or OE). Inferior frontal gyrus recruitment was more significant during SM than CM tasks in the E and O conditions. Compared to SM and FM, CM task resulted in increased recruitment of brain regions involved in complex motor task performance. Compared to O and E, OE resulted in the recruitment of additional, specific, brain areas in the cerebellum, temporal and parietal lobes. The modality of administration and the type of task modulated MNS recruitment during motor acts. This might have practical implications for the set-up of individualized motor rehabilitation strategies.

Action observation training modifies brain gray matter structure in healthy adult individuals.

Action observation training (AOT) is thought to facilitate motor system function. We applied voxelwise methods to assess the regional modifications of brain gray matter (GM) volumes and white matter (WM) architecture in healthy subjects following AOT and their correlations with improvements at motor and cognitive functional scales. Forty-two righ-handed healthy subjects were randomized into an experimental (AOT-G, n = 20) and a control (C-G, n = 22) group. The training lasted 2 weeks and consisted of 10 sessions of 45 min each during which subjects watched videos of daily-life actions (AOT-G) or landscapes (C-G), alternated by the execution with the right hand of actions presented in the AOT-G videos. At baseline and follow up, motor and cognitive functional measures as well as brain structural MRI scans were obtained. Tensor-based morphometry and tract-based spatial statistics were used to map longitudinal modifications of GM and WM structures and their correlation with functional scales. After training, both groups improved at cognitive tests, whereas the AOT-G also improved hand motor performance. Following training, no modifications of WM diffusion tensor MRI indexes were detected. After training, compared to C-G, AOT-G had increased volume of the left superior frontal gyrus and decreased volume of the right lingual gyrus. Compared to AOT-G, C-G showed increased volume of the right middle frontal gyrus and left inferior temporal gyrus. In AOT-G, GM volume changes correlated with improvements at cognitive tests. Ten-day AOT in healthy individuals modifies GM structure, promoting structural brain plasticity and functional competence.

Involvement of adenosine A1 and A2A receptors in (-)-linalool-induced antinociception.

In recent studies performed in our laboratory we have shown that acute administration of (-)-linalool, the natural occurring enantiomer in essential oils, possesses anti-inflammatory, antihyperalgesic and antinociceptive effects in different animal models. The antihyperalgesic and antinociceptive effects of (-)-linalool have been ascribed to its capacity in stimulating the opioidergic, cholinergic and dopaminergic systems, as well as to its interaction with K+ channels, or to its local anaesthetic activity and/or to the negative modulation of glutamate transmission. Activation of A1 or A2A receptors has been shown to induce antinociceptive effects, and the possible involvement of adenosine in (-)-linalool antinociceptive effect, has not been elucidated yet. Therefore, in the present study, we have investigated the effects of 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a selective adenosine A1 receptor antagonist and the effects of 3,7-dimethyl-1-propargilxanthine (DMPX), a selective adenosine A2A receptor antagonist on the antinociception of (-)-linalool in mice, measured in the hot-plate test. Both DPCPX (0.1 mg/kg; i.p.) and DMPX (0.1 mg/kg; i.p.) pre-treatment significantly depressed the antinociceptive effect of (-)-linalool at the highest doses tested. These findings demonstrated that the effect of (-)-linalool on pain responses is, at least partially, mediated by the activity of adenosine A1 and A2A receptors.

IL-22 is rapidly induced by Pathogen Recognition Receptors Stimulation in Bone-Marrow-derived Dendritic Cells in the Absence of IL-23.

In vertebrates, microorganisms are recognized by pathogen recognition receptors (PRRs). Exposure of immune cells to the ligands of these receptors activates intracellular signaling cascades that rapidly induce the expression of a variety of genes. Within these genes, the cytokines family plays a crucial function because of its role in adaptive immunity induction and in tissue-specific functional regulation, such as tissue repair and tissue homeostasis during steady state conditions. Within the myeloid compartment, dendritic cells (DCs) release a variety of inflammatory cytokines in response to microbes. In this study, we show that BMDCs release IL-22 directly upon PRRs activation without the need of IL-23 signaling as reported for other IL22-producing cells. Moreover, we demonstrate that cytokine IL-22 is rapidly released in a cell-specific manner as macrophages are not able to produce IL-22 through the same PRRs system. In addition, we characterize the intracellular signaling cascade required for IL-22 release in BMDCs. Myd88, MEK1/2, NFkb and AhR, but not p38, NFAT, and RORgt, were found to be involved in IL-22 regulation in DCs. Our study suggests that BMDCs possess a unique intracellular molecular plasticity which, once activated, directs different BMDCs functions in a cell-specific manner.