Transcranial Direct Current Stimulation Enhances Neuroplasticity and Accelerates Motor Recovery in a Stroke Mouse Model

BACKGROUND: More effective strategies are needed to promote poststroke functional recovery. Here, we evaluated the impact of bihemispheric transcranial direct current stimulation (tDCS) on forelimb motor function recovery and the underlying mechanisms in mice subjected to focal ischemia of the motor cortex. METHODS: Photothrombotic stroke was induced in the forelimb brain motor area, and tDCS was applied once per day for 3 consecutive days, starting 72 hours after stroke. Grid-walking, single pellet reaching, and grip strength tests were conducted to assess motor function. Local field potentials were recorded to evaluate brain connectivity. Western immunoblotting, ELISA, quantitative real-time polymerase chain reaction, and Golgi-Cox staining were used to uncover tDCS-mediated stroke recovery mechanisms. RESULTS: Among our results, tDCS increased the rate of motor recovery, anticipating it at the early subacute stage. In this window, tDCS enhanced BDNF (brain-derived neurotrophic factor) expression and dendritic spine density in the peri-infarct motor cortex, along with increasing functional connectivity between motor and somatosensory cortices. Treatment with the BDNF TrkB (tropomyosin-related tyrosine kinase B) receptor inhibitor, ANA-12, prevented tDCS effects on motor recovery and connectivity as well as the increase of spine density, pERK (phosphorylated extracellular signal-regulated kinase), pCaMKII (phosphorylated calcium/calmodulindependent protein kinase II), pMEF (phosphorylated myocyte-enhancer factor), and PSD (postsynaptic density)-95. The tDCSpromoted rescue was paralleled by enhanced plasma BDNF level, suggesting its potential role as circulating prognostic biomarker. CONCLUSIONS: The rate of motor recovery is accelerated by tDCS applied in the subacute phase of stroke. Anticipation of motor recovery via vicariate pathways or neural reserve recruitment would potentially enhance the efficacy of standard treatments, such as physical therapy, which is often delayed to a later stage when plastic responses are progressively lower

Entropy as Measure of Brain Networks’ Complexity in Eyes Open and Closed Conditions

Brain complexity can be revealed even through a comparison between two trivial conditions, such as eyes open and eyes closed (EO and EC respectively) during resting. Electroencephalogram (EEG) has been widely used to investigate brain networks, and several non-linear approaches have been applied to investigate EO and EC signals modulation, both symmetric and not. Entropy is one of the approaches used to evaluate the system disorder. This study explores the differences in the EO and EC awake brain dynamics by measuring entropy. In particular, an approximate entropy (ApEn) was measured, focusing on the specific cerebral areas (frontal, central, parietal, occipital, temporal) on EEG data of 37 adult healthy subjects while resting. Each participant was submitted to an EO and an EC resting EEG recording in two separate sessions. The results showed that in the EO condition the cerebral networks of the subjects are characterized by higher values of entropy than in the EC condition. All the cerebral regions are subjected to this chaotic behavior, symmetrically in both hemispheres, proving the complexity of networks dynamics dependence from the subject brain state. Remarkable dynamics regarding cerebral networks during simple resting and awake brain states are shown by entropy. The application of this parameter can be also extended to neurological conditions, to establish and monitor personalized rehabilitation treatments

Posterior densities of Fst genetic distances for the micro-evolutionary scenarios.

<p>Distributions of Fst values obtained by coalescent simulations (see Materials and Methods), with vertical lines representing observed values of within group diversity: (A) German speaking islands; (B) Italians (Non, Sole and Giudicarie valleys); (C) Ladins (continuous) and Italians (dashed; Fiemme, Fersina and Primiero valleys).</p

Multi-Dimensional Scaling plot of Fst genetic distances between Alpine and European populations.

<p>Plot based on 15 Y chromosome STRs (stress value=0.141). Population acronyms are given in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081704#pone-0081704-t001" target="_blank">Table 1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081704#pone.0081704.s009" target="_blank">Table S4</a>.</p

Plots of the genetic relations among populations under study.

<p>(a) Multi-Dimensional scaling plot of Fst genetic distances (15 STRs; stress value=0.128); (b) Principal Component Analysis plot based on haplogroup frequencies. First component (x axis) and second component (y axis) explain 16.96% and 13.95% of total variance, respectively. Acronyms are given in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081704#pone-0081704-t001" target="_blank">Table 1</a>.</p

Distribution of Fst genetic distances among Alpine, Sardinian, Basque, Finn and European populations.

<p>Frame A shows the Fst genetic distances distributions among European populations and between European and Alpine populations (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081704#pone.0081704.s009" target="_blank">Table S4</a>; Italy is represented only by La Spezia). Frame B shows the Fst genetic distances between some European outliers (Sardinians, Basques and Finns), Alpine groups and European open populations.</p

Geographic location of the populations under study (see table 1 for population acronyms).

<p>Geographic location of the populations under study (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081704#pone-0081704-t001" target="_blank">table 1</a> for population acronyms).</p

Nuova generazione di Internet e profili di organizzazione della PA nelle smart City. Aspetti etici e linee prospettiche di regolazione

Digitalizzazione, informatizzazione, innovazione ed integrazione tecnologica sono termini entrati prepotentemente a far parte del lessico quotidiano comune, contribuendo in modo radicale al cambiamento della vita di ciascun individuo ed al contempo proiettandolo verso una nuova dimensione sociale. Tale proiezione può essere definita come un passaggio obbligatorio dalla storia alla iperstoria (“La Quarta Rivoluzione. Come l’infosfera sta trasformando il mondo” (Floridi)). L’internet delle cose (IOT), il web 2.0, il cloud computing, i droni, la guida autonoma e le tante altre novità derivanti dall’ICT (Information Comunication Technology) ci stanno portando inesorabilmente verso la IV rivoluzione. Quindi, insieme alla biosfera, ci immergiamo nella infosfera, che ci avvolge e ci trasmette tutte le informazioni e i dati “processati” da montagne di algoritmi progettati per anticipare i nostri desideri e necessità. Ciò impone una maggiore cura delle questioni etiche, al fine di perseguire il necessario equilibrio tra le opportunità da cogliere e le inevitabili criticità connesse alla tecnologia adottata ed in continua evoluzione Il processo di digitalizzazione, ormai, permea ogni aspetto della vita quotidiana e, in questo quadro di profonda innovazione, anche le città sono destinate a cambiare in modo radicale

Breakthrough Cancer Pain: Preliminary Data of The Italian Oncologic Pain Multisetting Multicentric Survey (IOPS-MS)

Introduction: An ongoing national multicenter survey [Italian Oncologic Pain multiSetting Multicentric Survey (IOPS-MS)] is evaluating the characteristics of breakthrough cancer pain (BTP) in different clinical settings. Preliminary data from the first 1500 cancer patients with BTP enrolled in this study are presented here. Methods: Thirty-two clinical centers are involved in the survey. A diagnosis of BTP was performed by a standard algorithm. Epidemiological data, Karnofsky index, stage of disease, presence and sites of metastases, ongoing oncologic treatment, and characteristics of background pain and BTP and their treatments were recorded. Background pain and BTP intensity were measured. Patients were also questioned about BTP predictability, BTP onset (≤10 or >10 min), BTP duration, background and BTP medications and their doses, time to meaningful pain relief after BTP medication, and satisfaction with BTP medication. The occurrence of adverse reactions was also assessed, as well as mucosal toxicity. Results: Background pain was well controlled with opioid treatment (numerical rating scale 3.0 ± 1.1). Patients reported 2.5 ± 1.6 BTP episodes/day with a mean intensity of 7.5 ± 1.4 and duration of 43 ± 40 min; 977 patients (65.1%) reported non-predictable BTP, and 1076 patients (71.7%) reported a rapid onset of BTP (≤10 min). Higher patient satisfaction was reported by patients treated with fast onset opioids. Conclusions: These preliminary data underline that the standard algorithm used is a valid tool for a proper diagnosis of BTP in cancer patients. Moreover, rapid relief of pain is crucial for patients’ satisfaction. The final IOPS-MS data are necessary to understand relationships between BTP characteristics and other clinical variables in oncologic patients. Funding: Molteni Farmaceutici, Italy