Resveratrol Protects Cardiac Tissue in Experimental Malignant Hypertension Due to Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Properties.

Hypertension is one of the most prevalent and powerful contributors of cardiovascular diseases. Malignant hypertension is a relatively rare but extremely severe form of hypertension accompanied with heart, brain, and renal impairment. Resveratrol, a recently described grape-derived, polyphenolic antioxidant molecule, has been proposed as an effective agent in the prevention of cardiovascular diseases. This study was designed to examine chronic resveratrol administration on blood pressure, oxidative stress, and inflammation, with special emphasis on cardiac structure and function in two models of experimental hypertension. The experiments were performed in spontaneously (SHRs) and malignantly hypertensive rats (MHRs). The chronic administration of resveratrol significantly decreased blood pressure in both spontaneously and malignant hypertensive animals. The resveratrol treatment ameliorated morphological changes in the heart tissue. The immunohistochemistry of the heart tissue after resveratrol treatment showed that both TGF-ß and Bax were not present in the myocytes of SHRs and were present mainly in the myocytes of MHRs. Resveratrol suppressed lipid peroxidation and significantly improved oxidative status and release of NO. These results suggest that resveratrol prevents hypertrophic and apoptotic consequences induced by high blood pressure with more pronounced effects in malignant hypertension.

Transcranial direct current stimulation (tDCS) over parietal cortex improves associative memory.

Associative memory plays a key role in everyday functioning, but it declines with normal ageing as well as due to various pathological states and conditions, thus impairing quality of life. Associative memory enhancement via neurostimulation over frontal areas resulted in limited success, while posterior stimulation sites seemed to be more promising. We hypothesized that anodal transcranial direct current stimulation (tDCS) of parietal areas would lead to higher performance in associative memory due to high connectivity between posterior parietal cortex (PPC) and hippocampus. Forty-two healthy adults participated in two sham-controlled cross-over experiments. Anodal electrode (20 min, 1.5 mA) was placed over P3 in Experiment 1 and over P4 in Experiment 2. During tDCS participants played a simple computer game. After each stimulation session, participants completed parallel forms of an associative memory task (Experiment 1: face-word memory; Experiment 2: object-location memory) and a control task (verbal fluency). In both experiments, associative memory was improved after anodal stimulation compared to sham stimulation, while no differences were observed in the control task. Additionally, memory performance was higher in the second than in the first trial, but the increase in performance between the two trials did not differ between stimulation conditions. It can be concluded that a single-session anodal tDCS over posterior parietal cortex can improve associative memory performance. The specificity, robustness, and reproducibility of the effect suggest that PPC is a promising target for brain stimulation aiming to enhance memory functions.

Sport-Specific Warm-Up Attenuates Static Stretching- Induced Negative Effects on Vertical Jump But Not Neuromuscular Excitability in Basketball Players.

The purpose of this study was to examine the acute effects of static stretching (SS) and dynamic stretching (DS), alone and in combination with specific basketball warm-up (SBWU), on the neuromuscular excitability and vertical jump height in basketball players. Twelve healthy young male basketball players participated in the study (18 ± 0.42 years; 17.4 - 18.6 age range; 188 ± 9 cm; 76.5 ± 9 kg). All participants completed two different stretching treatments (static and dynamic), performed on different days at least seven days apart, in the same period of training microcycle, in a counterbalanced order. Each session consisted of a self-paced jogging warm-up, followed by a 10-minute testing period (T0), which involved eliciting H reflex and M waves, followed by three trials of a vertical jump test. Participants then performed one of the treatment protocols. After another test (T1), participants conducted 8-minute specific basketball warm-up and then one more test (T2). Combined 3 (time) x 2 (stretching protocol) analysis of variance with repeated measures on both factors revealed that SS significantly decreased spinal excitability (H/M ratio) (p = 0.015, d = -0.38, percentage of change = -20.55%) and vertical jump height (p = 0.007, d = -1.91, percentage of change = -2.6%), but after SBWU, vertical jump height increased (p = 0.006, d = 1.13, percentage of change = 3.01%), while H/M ratio continued decreasing (p = 0.019, d = -0.45, percentage of change = -30.23%). Acute effects of DS, alone and in combination with SBWU were not significant. It seems that SBWU attenuates negative acute effects of SS on vertical jump performance in young basketball players, while DS appears to cause no significant acute effect for this population.

Improvement of language functions in a chronic non-fluent post-stroke aphasic patient following bilateral sequential theta burst magnetic stimulation.

In chronic non-fluent aphasia patients, inhibition of the intact right hemisphere (RH), by transcranial magnetic stimulation (TMS) or similar methods, can induce improvement in language functions. The supposed mechanism behind this improvement is a release of preserved left hemisphere (LH) language networks from RH transcallosal inhibition. Direct stimulation of the damaged LH can sometimes bring similar results too. Therefore, we developed a novel treatment approach that combined direct LH (Broca's area (BA)) stimulation, by intermittent theta burst stimulation (TBS), with homologue RH area's inhibition, by continuous TBS. We present the results of application of 15 daily sessions of the described treatment approach in a right-handed patient with chronic post-stroke non-fluent aphasia. The intervention appeared to improve several language functions, but most notably propositional speech, semantic fluency, short-term verbal memory, and verbal learning. Bilateral TBS modulation of activation of the language-related areas of both hemispheres seems to be a feasible and promising way to induce recovery in chronic aphasic patients. Due to potentially cumulative physiological effects of bilateral stimulation, the improvements may be even greater than following unilateral interventions.

Transcranial application of near-infrared low-level laser can modulate cortical excitability.

BACKGROUND AND OBJECTIVE: Near-infrared low-level laser (NIR-LLL) irradiation penetrates scalp and skull and can reach superficial layers of the cerebral cortex. It was shown to improve the outcome of acute stroke in both animal and human studies. In this study we evaluated whether transcranial laser stimulation (TLS) with NIR-LLL can modulate the excitability of the motor cortex (M1) as measured by transcranial magnetic stimulation (TMS). METHODS: TLS was applied for 5 minutes over the representation of the right first dorsal interosseal muscle (FDI) in left primary motor cortex (M1), in 14 healthy subjects. Motor evoked potentials (MEPs) from the FDI, elicited by single-pulse TMS, were measured at baseline and up to 30 minutes after the TLS. RESULTS: The average MEP size was significantly reduced during the first 20 minutes following the TLS. The pattern was present in 10 (71.5%) of the participants. The MEP size reduction correlated negatively with the motor threshold at rest. CONCLUSIONS: TLS with NIR-LLL induced transitory reduction of the excitability of the stimulated cortex. These findings give further insights into the mechanisms of TLS effects in the human cerebral cortex, paving the way for potential applications of TLS in treatment of stroke and in other clinical settings.

Resveratrol improved kidney function and structure in malignantly hypertensive rats by restoration of antioxidant capacity and nitric oxide bioavailability.

BACKGROUND: The main cause of death among patients with malignant hypertension is a kidney failure. The promising field in essential and malignant hypertension therapy could be centered on the amelioration of oxidative stress using antioxidant molecules like resveratrol. Resveratrol is a potent antioxidative agent naturally occurred in many plants that possess health-promoting properties. METHODS: In the present study, we investigated the therapeutic potential of resveratrol, a polyphenol with anti-oxidative activity, in NG-L-Arginine Methyl Ester (L-NAME) treated spontaneously hypertensive rats (SHR) - malignantly hypertensive rats (MHR). RESULTS: Resveratrol significantly improves oxidative damages by modulation of antioxidant enzymes and suppression of prooxidant factors in the kidney tissue of MHR. Enhanced antioxidant defense in the kidney improves renal function and ameliorates the morphological changes in this target organ. Besides, protective properties of resveratrol are followed by the restoration of the nitrogen oxide (NO) pathway. 4) Conclusion: Antioxidant therapy with resveratrol could represent promising therapeutical approach in hypertension, especially malignant, against kidney damage.

Changes in cortical excitability during paired associative stimulation in Parkinson's disease patients and healthy subjects.

Paired associative stimulation (PAS) combines repetitive peripheral nerve stimulation with motor cortex (M1) transcranial magnetic stimulation (TMS), to induce plastic-like changes of cortical excitability. While much attention has been dedicated to post-PAS effects little is known about processes during PAS. We compared the time-course of changes in M1 excitability during standard facilitatory PAS intervention among patients with Parkinson's disease (PD), known to have diminished post-PAS response, and healthy subjects. Compared to baseline pre-PAS MEPs, conditioned MEPs during PAS decreased significantly in both groups. The decrease was significantly larger in healthy subjects than in PD patients, regardless whether patients were drug-naïve or not. Although post-PAS excitability increase was also larger in healthy subjects than in PD patients, there was no significant correlation between the two phenomena, i.e. the extent of MEP decrease during PAS and the extent of the post-PAS excitability increase. The results highlight an apparent physiological paradox that repetitive application of an inhibitory stimulation pattern leads to subsequent prolonged facilitation, thus broadening the understanding of the phenomenology of PAS response. Results also suggest that in PD cortical circuits involved in conveying inhibition during PAS, are impaired at the clinical onset of the disease and are not influenced by subsequent PD treatment.

Bilateral sequential motor cortex stimulation and skilled task performance with non-dominant hand.

OBJECTIVE: To check whether bilateral sequential stimulation (BSS) of M1 with theta burst stimulation (TBS), using facilitatory protocol over non-dominant M1 followed by inhibitory one over dominant M1, can improve skilled task performance with non-dominant hand more than either of the unilateral stimulations do. Both, direct motor cortex (M1) facilitatory non-invasive brain stimulation (NIBS) and contralateral M1 inhibitory NIBS were shown to improve motor learning. METHODS: Forty right-handed healthy subjects were divided into 4 matched groups which received either ipsilateral facilitatory (intermittent TBS [iTBS] over non-dominant M1), contralateral inhibitory (continuous TBS [cTBS] over dominant M1), bilateral sequential (contralateral cTBS followed by ipsilateral iTBS), or placebo stimulation. Performance was evaluated by Purdue peg-board test (PPT), before (T0), immediately after (T1), and 30min after (T2) an intervention. RESULTS: In all groups and for both hands, the PPT scores increased at T1 and T2 in comparison to T0, showing clear learning effect. However, for the target non-dominant hand only, immediately after BSS (at T1) the PPT scores improved significantly more than after either of unilateral interventions or placebo. CONCLUSION: M1 BSS TBS is an effective intervention for improving motor performance. SIGNIFICANCE: M1 BSS TBS seems as a promising tool for motor learning improvement with potential uses in neurorehabilitation.

Effects of anodal tDCS and occupational therapy on fine motor skill deficits in patients with chronic stroke.

BACKGROUND: A growing body of evidence supports the effectiveness of using transcranial direct current stimulation (tDCS) in patients with chronic hand motor impairment resulting from stroke. OBJECTIVE: In this study, we investigate and compare the combined effects of anodal tDCS and occupational therapy (OT) to sham stimulation with OT (control) on fine motor skill deficits of chronic stroke patients. METHODS: A total of 26 stroke patients (at ≥ 9 months) were randomly assigned to an active treatment or a control group in a double-blinded, sham-controlled, parallel design study. Each group received OT for 45 min/day (10 sessions for 2 weeks). Treatment was preceded by either 20 minutes of 2 mA anodal tDCS over ipsilesional M1 or sham tDCS. A modified Jebsen-Taylor Hand Function Test (mJTHFT) was administered as primary outcome measure, and handgrip dynamometer and upper limb Fugl-Meyer (ULFM) assessments were performed as secondary outcomes. The assessment was done at baseline (T0), after the interventions on day 1(T1), day 10 (T2) and day 40 (T3). RESULTS: We observed a statistically significant effect in the tDCS group when the results were compared to the sham group. The mJTHFT times were significantly shorter immediately after treatment and at day 40. The intervention had no effect on handgrip strength or ULFM score. CONCLUSION: Fine motor skill deficits in chronic stroke survivors can be improved when intensive OT is primed with anodal tDCS over the ipsilesional hemisphere.

Differential effects of facilitatory and inhibitory theta burst stimulation of the primary motor cortex on motor learning.

OBJECTIVE: To evaluate the differential effects on motor learning of two types of theta burst stimulation (TBS), the excitatory intermittent TBS (iTBS) and inhibitory continuous TBS (cTBS), if TBS is applied in an early stage of learning process. METHODS: Thirty right handed healthy people were randomly allocated into one of the three groups according to the intervention applied, iTBS, cTBS or placebo. The interventions and measurements targeted the non-dominant side. The reaction time task (RTT) and Purdue pegboard task (PPT) were used. Measurements and motor tasks were carried out at baseline (T0), immediately after the intervention (T1), and 30 min later (T2). RESULTS: Compared to placebo, following cTBS M1 excitability went down and PPT learning was slowed. Following iTBS M1 excitability increased temporarily and PPT learning pattern changed, but learning was not improved. The MEP and PPT changes induced during the T0-T1 time interval correlated significantly. CONCLUSIONS: The early consolidation of the learned material was much more influenced by the TBS induced promotion/suppression of the M1 functional plasticity reserves than by the absolute level of the M1 activation. SIGNIFICANCE: The results may help to better define the use of TBS in promotion of motor learning in neurorehabilitation and cognitive enhancement.

Transcranial magnetic stimulation has no placebo effect on motor learning.

OBJECTIVE: Motor learning is the core cognitive function in neurorehabilitation and in various other skill-training activities (e.g. sport, music). Therefore, there is an increasing interest in the use of transcranial magnetic stimulation (TMS) methods for its enhancement. However, although usually assumed, a potential placebo effect of TMS methods on motor learning has never been systematically investigated. METHODS: Improvement of performance on the Purdue Pegboard Task over three test-blocks (T0, T1, and T2), separated by >20 min, was used to evaluate motor learning. In Experiment-1, two groups of 10 participants each were compared: one group immediately before T1 received a sham intermittent theta burst stimulation procedure (P-iTBS group), while another did not have any intervention at all (control - CON group). In Experiment-2, a third group of participants (six subjects) who received sham high-frequency repetitive TMS procedure before T1 (P-rTMS group) was compared with P-iTBS group. RESULTS: All three groups showed significant learning over time, but without any difference between them, either in Experiment-1 between P-iTBS and CON, or in Experiment-2 between P-rTMS and P-iTBS. CONCLUSION: The results suggest lack of any placebo effect of TMS on motor learning. SIGNIFICANCE: The results may help in designing further TMS-motor learning studies and in interpreting their results.