Search

Background: Along with conventional therapy, novel tools are being developed in balance training for the rehabilitation of persons with stroke sequelae. The efficacy of Computerized Balance Training thus far been the object of studies only in persons with chronic stroke. Objective: To investigate the effects of an early Computerized Balance Training on balance, walking endurance and independence in activities of daily living, in persons with mild hemiparesis in subacute phase. Methods: Thirty-two persons with a recent hemiparesis (within 4 weeks from stroke onset), able to maintain a standing position for at least 30 seconds, were randomly assigned to an experimental or control group. The control group (CG) were administered conventional physiotherapy of 40 minutes twice a day, 5 times a week for 4 weeks, while the experimental group (EG) underwent conventional physiotherapy 40 minutes once a day and Computerized Balance Training once a day, 5 times a week for 4 weeks. Outcomes were evaluated by means of Berg Balance Scale (BBS), Tinetti Balance Scale (TBS), Two Minutes Walk Test (2MWT), Barthel Index (BI) and stabilometric tests. Results: Twelve participants for each group completed the training. Each group experienced 8 dropouts. The mean age (years) was 58.1±20.4 for EG and 59.7±14,7 for CG; the days from stroke were respectively 27.9±15.5 and 20±11.7. The difference between the two groups was statistically significant in experimental group for BBS (p = 0.003), for TBS (p = 0.028), for Sensory Integration and Balance tests performed with closed eyes on steady (p = 0.009) or instable surface (p = 0.023). and for 2MWT (p = 0.008). Conclusions: Computerized Balance Training is an effective therapeutic tool for balance and gait endurance improvement in persons with stroke in subacute phase. [ABSTRACT FROM AUTHOR]

Background: The leap motion controller (LMC) is a new optoelectronic system for capturing motion of both hands and controlling a virtual environment. Differently from previous devices, it optoelectronically tracks the fine movements of fingers neither using glows nor markers. Objective: This pilot study explored the feasibility of adapting the LMC, developed for videogames, to neurorehabilitation of elderly with subacute stroke. Methods: Four elderly patients (71.50 ± 4.51 years old) affected by stroke in subacute phase were enrolled and tested in a cross-over pilot trial in which six sessions of 30 minutes of LMC videogame-based therapy were added on conventional therapy. Measurements involved participation to the sessions, evaluated by means of the Pittsburgh Rehabilitation Participation Scale, hand ability and grasp force evaluated respectively by means of the Abilhand Scale and by means of the dynamometer. Results: Neither adverse effects nor spasticity increments were observed during LMC training. Participation to the sessions was excellent in three patients and very good in one patient during the LMC trial. In this period, patients showed a significantly higher improvement in hand abilities (P=0.028) and grasp force (P=0.006). Conclusions: This feasibility pilot study was the first one using leap motion controller for conducting a videogame-based therapy. This study provided a proof of concept that LMC can be a suitable tool even for elderly patients with subacute stroke. LMC training was in fact performed with a high level of active participation, without adverse effects, and contributed to increase the recovery of hand abilities. [ABSTRACT FROM AUTHOR]

A2A adenosine receptor antagonists are currently under investigation as potential therapeutic agents for Parkinson's disease (PD). However, the molecular mechanisms underlying this therapeutic effect is still unclear. A functional antagonism exists between A2A adenosine and D2 dopamine (DA) receptors that are coexpressed in striatal medium spiny neurons (MSNs) of the indirect pathway. Since this interaction could also occur in other neuronal subtypes, we have analyzed the pharmacological modulation of this relationship in murine MSNs of the direct and indirect pathways as well in striatal cholinergic interneurons. Under physiological conditions, endogenous cannabinoids (eCBs) play a major role in the inhibitory effect on striatal glutamatergic transmission exerted by the concomitant activation of D2 DA receptors and blockade of A2A receptors in both D2- and D1-expressing striatal MSNs. In experimental models of PD, the inhibition of striatal glutamatergic activity exerted by D2 receptor activation did not require the concomitant inhibition of A2A receptors, while it was still dependent on the activation of CB1 receptors in both D2- and D1-expressing MSNs. Interestingly, the antagonism of M1 muscarinic receptors blocked the effects of D2/A2A receptor modulation on MSNs. Moreover, in cholinergic interneurons we found coexpression of D2 and A2A receptors and a reduction of the firing frequency exerted by the same pharmacological agents that reduced excitatory transmission in MSNs. This evidence supports the hypothesis that striatal cholinergic interneurons, projecting to virtually all MSN subtypes, are involved in the D2/A2A and endocannabinoid-mediated effects observed on both subpopulations of MSNs in physiological conditions and in experimental PD. [ABSTRACT FROM AUTHOR]

Dystonia pathophysiology has been partly linked to downregulation and dysfunction of dopamine D2 receptors in striatum. We aimed to investigate the possible morpho-structural correlates of D2 receptor downregulation in the striatum of a DYT1 Tor1a mouse model. Adult control Tor1a+/+ and mutant Tor1a+/− mice were used. The brains were perfused and free-floating sections of basal ganglia were incubated with polyclonal anti-D2 antibody, followed by secondary immune-fluorescent antibody. Confocal microscopy was used to detect immune-fluorescent signals. The same primary antibody was used to evaluate D2 receptor expression by western blot. The D2 receptor immune-fluorescence appeared circumscribed in small disks (~0.3–0.5 µm diameter), likely representing D2 synapse aggregates, densely distributed in the striatum of Tor1a+/+ mice. In the Tor1a+/− mice the D2 aggregates were significantly smaller (µm2 2.4 ± SE 0.16, compared to µm2 6.73 ± SE 3.41 in Tor1a+/+) and sparse, with ~30% less number per microscopic field, value correspondent to the amount of reduced D2 expression in western blotting analysis. In DYT1 mutant mice the sparse and small D2 synapses in the striatum may be insufficient to "gate" the amount of presynaptic dopamine release diffusing in peri-synaptic space, and this consequently may result in a timing and spatially larger nonselective sphere of influence of dopamine action. [ABSTRACT FROM AUTHOR]

Abstract: Huntington''s disease (HD) is a progressive neurodegenerative disorder, characterised by severe degeneration of basal ganglia, motor abnormalities, impaired cognitive function and emotional disturbances. Many of the distinct neuropathological features of HD are reproduced in rats by intrastriatal injections of the excitotoxin quinolinic acid (QA), and QA-induced excitotoxicity is partially prevented by administration of the A2A receptor antagonist prior to the QA injection. In this study, we assessed the neuroprotective effects of the adenosine A2A receptor antagonist SCH 58261 on the progressive behavioural alterations reported in the QA rat model of Huntington''s disease. Male rats received i.p. SCH 58261 (0.01mg/kg) or vehicle 20min before a bilateral injection of quinolinic acid (QA, 300nmol/1μl) or its vehicle in the dorsal striatum. Motor activity and anxiety levels were analyzed in an open-field arena and in an elevated plus-maze at 2 weeks, 2 months and 6 months post-lesion. In QA-lesioned rats SCH 58261 prevented alterations of wall rearing behaviour starting from 2 weeks post-lesion while emotional changes (reduced anxiety) were back to control levels by 6 months post-lesion. These findings extend to the behavioural parameters the protective effects of SCH 58261 in the QA model of Huntington''s disease. [Copyright &y& Elsevier]

Cognitive impairment is common in multiple sclerosis (MS). Unfortunately, the synaptic and molecular mechanisms underlying MS-associated cognitive dysfunction are largely unknown. We explored the presence and the underlying mechanism of cognitive and synaptic hippocampal dysfunction during the remission phase of experimental MS. Experiments were performed in a chronic-relapsing experimental autoimmune encephalomyelitis (EAE) model of MS, after the resolution of motor deficits. Immunohistochemistry and patch-clamp recordings were performed in the CA1 hippocampal area. The hole-board was utilized as cognitive/behavioural test. In the remission phase of experimental MS, hippocampal microglial cells showed signs of activation, CA1 hippocampal synapses presented an impaired long-term potentiation (LTP) and an alteration of spatial tests became evident. The activation of hippocampal microglia mediated synaptic and cognitive/behavioural alterations during EAE. Specifically, LTP blockade was found to be caused by the reactive oxygen species (ROS)-producing enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We suggest that in the remission phase of experimental MS microglia remains activated, causing synaptic dysfunctions mediated by NADPH oxidase. Inhibition of microglial activation and NADPH oxidase may represent a promising strategy to prevent neuroplasticity impairment associated with active neuro-inflammation, with the aim to improve cognition and counteract MS disease progression.

A(2A) adenosine receptor antagonists are currently under investigation as potential therapeutic agents for Parkinson's disease (PD). However, the molecular mechanisms underlying this therapeutic effect is still unclear. A functional antagonism exists between A(2A) adenosine and D(2) dopamine (DA) receptors that are coexpressed in striatal medium spiny neurons (MSNs) of the indirect pathway. Since this interaction could also occur in other neuronal subtypes, we have analyzed the pharmacological modulation of this relationship in murine MSNs of the direct and indirect pathways as well in striatal cholinergic interneurons. Under physiological conditions, endogenous cannabinoids (eCBs) play a major role in the inhibitory effect on striatal glutamatergic transmission exerted by the concomitant activation of D(2) DA receptors and blockade of A(2A) receptors in both D(2)- and D(1)-expressing striatal MSNs. In experimental models of PD, the inhibition of striatal glutamatergic activity exerted by D(2) receptor activation did not require the concomitant inhibition of A(2A) receptors, while it was still dependent on the activation of CB(1) receptors in both D(2)- and D(1)-expressing MSNs. Interestingly, the antagonism of M1 muscarinic receptors blocked the effects of D(2)/A(2A) receptor modulation on MSNs. Moreover, in cholinergic interneurons we found coexpression of D(2) and A(2A) receptors and a reduction of the firing frequency exerted by the same pharmacological agents that reduced excitatory transmission in MSNs. This evidence supports the hypothesis that striatal cholinergic interneurons, projecting to virtually all MSN subtypes, are involved in the D(2)/A(2A) and endocannabinoid-mediated effects observed on both subpopulations of MSNs in physiological conditions and in experimental PD.