Systemic Administration of Mesenchymal Stem Cells Increases Neuron Survival after Global Cerebral Ischemia In Vivo (2VO)

Although many studies have shown that administration of stem cells after focal cerebral ischemia improves brain damage, very little data are available concerning the damage induced by global cerebral ischemia. The latter causes neuronal death in selectively vulnerable areas, including the hippocampal CA1 region. We tested the hypothesis that intravenous infusion of bone marrowderived stromal cells (mesenchimal stem cells, MSC) reduce brain damage after transient global ischemia. In adult male Sprague-Dawley rats transient global ischemia was induced using bilateral common carotid artery occlusion for 20 min in addition to controlled hypotension. Five days after, the animals were anaesthetized with urethane and the brain was fixed, sectioned and stained with hematoxylin-eosin to investigate histological damage. MSC did not fully protect against ischemic damage, as the number of viable neurons in this group was lower than in normal (sham-operated) rats. However, in MSC-treated rats the number of viable CA1 pyramidal neurons was significally higher than in rats that had been subjected to ischemia but not treated with MSC. We conclude that intravenous administration of MSC after transient global ischemia reduces hippocampal damage

Action Observation Combined With Conventional Training Improves the Rugby Lineout Throwing Performance: A Pilot Study

Combining action observation (AO) and physical practice contributes to motor skill learning, and a number of studies pointed out the beneficial role of AO training in improving the motor performance and the athletes' movement kinematics. The aim of this study was to investigate if AO combined with immediate conventional training was able to improve motor performance and kinematic parameters of a complex motor skill such as the lineout throw, a gesture that represents a key aspect of rugby, that is unique to this sport. Twenty elite rugby players were divided into two groups. The AO group watched a 5-min video-clip of an expert model performing the lineout throw toward a target at 7 m distance and, immediately after the AO, this group executed the conventional training, consisting of six repetitions x five blocks of throws. The CONTROL group performed only the conventional lineout training. Intervention period lasted 4 weeks, 3 sessions/week. The AO group showed significant improvements in throwing accuracy (i.e., number of throws hitting the target), whilst no significant changes were observed in the CONTROL group. As concerns kinematic parameters, hooker's arm mean velocity significantly increased in both groups, but the increase was higher in AO group compared to CONTROL group. Ball velocity significantly increased only in the AO group, whereas ball angle release and ball spinning significantly decreased in both groups, with no differences between groups. Finally, no significant changes in knee and elbow angles were observed. Our results showed that the combination of AO and conventional training was more effective than a conventional training alone in improving the performance of elite rugby players, in executing a complex motor skill, such as the lineout. This combined training led to significant improvements in throwing accuracy and in hooker's and ball's kinematic parameters. Since AO can be easily implemented in combination with conventional training, the results of this study can encourage coaches in designing specific lineout training programs, which include AO cognitive training

Therapeutic use of creatine in brain or heart ischemia: available data and future perspectives.

Creatine (Cr) is essential in safeguarding ATP levels and in moving ATP from its production site (mitochondria) to the cytoplasmic regions where it is used. Moreover, it has effects unrelated to energy metabolism, such as free radical scavenging, antiapoptotic action, and protection against excitotoxicity. Recent research has studied Cr-derived compounds (Cr benzyl ester and phos-pho-Cr-magnesium complex) that reproduce the neuroprotective effects of Cr while better crossing the neuronal plasma membrane and, hopefully, the blood-brain barrier (BBB). Intracellular levels of Cr can be increased by incubation with Cr or some of its derivatives, and this increase is protective against anoxic or ischemic damage. A large amount of experimental evidence shows that pretreatment with Cr is capable of reducing the damage induced by ischemia or anoxia in both heart and brain, and that such treatment may also be useful even after stroke or myocardial infarction (MI) has already occurred. Cr has been safely administered to patients affected by several neurological diseases, yet it has never been tested in human brain ischemia, the condition where its rationale is strongest. Phosphocreatine (PCr) has been administered after human MI, where it proved to be safe and probably helpful. Cr should be tested in the prophylactic protection against human brain ischemia and either Cr or PCr should be further tested in MI. Moreover, Cr- or PCr-derived drugs should be developed in order to overcome these molecules' limitations in crossing the BBB and the cell plasma membrane

Calpain-1 resident in lipid raft/caveolin-1 membrane microdomains plays a protective role in endothelial cells.

We are here reporting that calpain-1 is a constitutive component of a distinct lipid raft/caveolin-1 microdomain isolated from bEnd5 cells in association with endothelial nitric oxide synthase (eNOS) and heat shock protein 90 (HSP90). Perturbations in intracellular calcium concentration by Ca2+-ionophore A23187 or prolonged cell exposure to high glucose induce a significant decrease in the level of eNOS accompanied by a recruitment of additional HSP90 molecules at this site. In these conditions the cells are more resistant to cell death by Ca2+ overload. The decrease of eNOS has been due not only to its Ca2+-mediated release from the caveolin-1 aggregates but also to its digestion by calpain-1. The specific involvement of calpain-1 in digestion of eNOS is supported by the preventive effect of a synthetic calpain inhibitor (CI-2) and by the absence of calpain-2 and calpastatin in the caveolin-1 microdomain. These results suggest that the protein adjustments observed in lipid raft/caveolin-1 microdomains could be visualized as a process required to protect the cells against NO overproduction and aberrant calpain activation. Alterations in eNOS, calpain-1 and HSP90 levels have been observed in aorta of Zucker Diabetic Rats (ZDR). The loss of HSP90 occurring in these animals indicates an aberrant activation of calpain and thereby the transition from a physiological to a pathological cell condition

Action observation: Mirroring across our spontaneous movement tempo

During action observation (AO), the activity of the “mirror system” is influenced by the viewer’s expertise in the observed action. A question that remains open is whether the temporal aspects of the subjective motor repertoire can influence the “mirror system” activation

IVGTT-based simple assessment of glucose tolerance in the Zucker fatty rat: Validation against minimal models

For the assessment of glucose tolerance from IVGTT data in Zucker rat, minimal model methodology is reliable but time- and money-consuming. This study aimed to validate for the first time in Zucker rat, simple surrogate indexes of insulin sensitivity and secretion against the glucose-minimal-model insulin sensitivity index (SI) and against first- (φ1) and second-phase (φ2) β-cell responsiveness indexes provided by C-peptide minimal model. Validation of the surrogate insulin sensitivity index (ISI) and of two sets of coupled insulinbased indexes for insulin secretion, differing from the cut-off point between phases (FPIR3- SPIR3, t = 3 min and FPIR5- SPIR5, t = 5 min), was carried out in a population of ten Zucker fatty rats (ZFR) and ten Zucker lean rats (ZLR). Considering the whole rat population (ZLR+ZFR), ISI showed a significant strong correlation with SI (Spearman's correlation coefficient, r = 0.88; P<0.001). Both FPIR3 and FPIR5 showed a significant (P<0.001) strong correlation with φ1 (r = 0.76 and r = 0.75, respectively). Both SPIR3 and SPIR5 showed a significant (P<0.001) strong correlation with φ2 (r = 0.85 and r = 0.83, respectively). ISI is able to detect (P<0.001) the well-recognized reduction in insulin sensitivity in ZFRs, compared to ZLRs. The insulin-based indexes of insulin secretion are able to detect in ZFRs (P<0.001) the compensatory increase of first- and second-phase secretion, associated to the insulinresistant state. The ability of the surrogate indexes in describing glucose tolerance in the ZFRs was confirmed by the Disposition Index analysis. The model-based validation performed in the present study supports the utilization of low-cost, insulin-based indexes for the assessment of glucose tolerance in Zucker rat, reliable animal model of human metabolic syndrome

Boosting and consolidating the proprioceptive cortical aftereffect by combining tendon vibration and repetitive TMS over primary motor cortex

Tendon vibration of a limb elicits illusory movements in the direction that the vibrated muscle would be stretched, followed by a transient perception of movement in the opposite direction, that was demonstrated to correspond to a \u201ccortical\u201d aftereffect (Goodwin et al. Science 175:1382\u20131384, 1972). Primary motor cortex (M1) excitability of the non-vibrated antagonist muscle of the vibrated muscle increased during vibration and decreased thereafter. The cortical aftereffect is of interest when considering the possibility to use tendon vibration in rehabilitation for restoring unbalance activity between antagonistic muscles but, due to its short-lasting duration, has not been explored so far. We investigated the possibility to consolidate the cortical aftereffect by combining tendon vibration with a concomitant high-frequency 5-Hz repetitive transcranial magnetic stimulation (rTMS) protocol. The distal tendon of the flexor carpi radialis muscle (FCR) was vibrated and concomitantly a 2-min 5-Hz rTMS protocol was administered on the left hemi-scalp hot spot of the vibrated FCR or its antagonist muscle (extensor carpi radialis (ECR)). We found that this protocol induced a pattern of unbalanced M1 excitability between vibrated muscle and its antagonist with increased excitability of the FCR and decreased excitability of ECR cortical areas, which persisted up to 30&nbsp;min

Acute and Chronic Catabolic Responses to CrossFit® and Resistance Training in Young Males

Given the wide variety of conditioning program trainings employed, the present study compared the catabolic effects induced by CrossFit&reg; and resistance training in moderately trained subjects. Twenty males joined either the CrossFit&reg; group (n = 10; 30 min/day of &ldquo;workout of the day&rdquo;) or the resistance training (RT) group (n = 10; 30 min/day of resistance exercises) thrice a week, for 8 weeks. Salivary levels of cortisol, interleukin 1-beta (IL-1&beta;), and uric acid were assessed via enzyme-linked immunosorbent assays before (PRE) and 30-min after (POST) SESSION 1 and SESSION 24. Variables&rsquo; percentual changes were computed as (POST-PRE)/PRE*100 in each session (&Delta;%). CrossFit&reg; acutely increased cortisol levels in both sessions, with a significant decrease in &Delta;%cortisol from SESSION 1 to 24. In the RT group, cortisol values decreased in both sessions, only acutely. A significant decrease in IL-1&beta; levels was registered acutely in both groups, in both sessions, whereas &Delta;%IL-1&beta; was not different between the two groups. While uric acid levels increased in both groups acutely, a chronic downregulation of &Delta;%uric acid, from SESSION 1 to 24, was appreciated for the RT group only. Overall, CrossFit&reg; appeared to induce more intense effects than the RT program as to the investigated catabolic responses