Hamstrings-quadriceps strength ratio could be related to falls in community-living older adults.

A prior study reported that the concentric strength imbalance between hamstrings and quadriceps is associated with falls in older adults. Given that the concentric strength may not be measured as conveniently as the isometric strength, it is meaningful to test whether the isometric hamstring-quadricep strength imbalance is related to falls among older adults. This study sought to explore whether the hamstrings-quadriceps ratio could differentiate fallers from non-fallers in community-dwelling older adults. One hundred and eleven older adults were included in this cross-sectional study. Their isometric knee joint strength capacity (extensors and flexors) was measured. Based on their fall history in the past year, they were classified as fallers (at least one fall) or non-fallers (no fall). The hamstrings-quadriceps ratio was compared between the faller and non-faller groups. The receiver operating characteristic analysis was used to determine the cutoff value of the hamstrings-quadriceps ratio able to best classify fallers and non-fallers. Fallers showed a significantly lower hamstrings-quadriceps ratio than non-fallers (p = 0.008). The receiver operating characteristic analysis identified 0.733 as the best ratio to differentiate fallers from non-fallers with an accuracy of 64.0 %. A 0.1-unit reduction in the hamstrings-quadriceps ratio increases the probability of falling by a factor of 1.30. The hamstrings-quadriceps ratio could be used as an additional fall risk factor when assessing the risk of falls among older adults. A smaller than 0.733 hamstring-quadriceps ratio may indicate a high risk of falls.

Nordic walking and arm swing asymmetry in people with Parkinson's disease: protocol for a randomised clinical trial.

People with Parkinson's disease (PD) face disruptions in arm swing (AS) motion during walking, including a reduction in amplitude and an increase in asymmetry. Both conditions are detrimental to gait performance. Nordic walking (NW) is a walking modality that uses poles and can positively affect the parameters of AS. This study aims to compare an NW with a free walking (FW) protocol and investigate its effects on AS asymmetry, AS amplitude and gait parameters in people with PD. Twenty-eight people with PD, stages 1-3 on the Hoehn and Yahr Scale, will be randomly assigned to the NW training group (n=14) or the FW training group (n=14). The primary outcomes are amplitude asymmetry of AS (%) and AS amplitude (deg). We will also analyse temporospatial measurements during walking, functional mobility and quality of life. Blinded researchers will conduct evaluations at baseline (T0), postintervention (T1) and at 1 month follow-up (T2). Participants will complete 24 supervised NW or FW training sessions for 12 weeks. This is the first study to address the effects of NW on the asymmetry of AS, AS amplitude and its influence on gait parameters. We hypothesise that an NW programme in PD will reduce the asymmetry and increase the AS amplitude during gait to a greater extent than FW. The results of this study may provide new evidence to understand the effects of NW on gait in people with PD. The study was registered in ClinicalTrial.gov (NCT06342271).

Movement strategies during obstacle crossing in people with Parkinson disease: A systematic review with meta-analysis.

OBJECTIVE: Navigating obstacles involves adjusting walking patterns, particularly when stepping over them. This task may be particularly challenging for people with Parkinson disease (PD) for several reasons. This review aims to compare the spatiotemporal gait parameters of people with and without PD while stepping over obstacles. LITERATURE SURVEY: A systematic literature search was conducted in six databases (PubMed, Scopus, Web of Science, EBSCO, Embase, and SciELO) from inception to September 2023. METHODOLOGY: Studies were selected that evaluated gait parameters of people with and without PD while walking over obstacles. Two independent researchers evaluated the eligibility and extracted gait parameters during obstacle crossing. The risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Heterogeneity was assessed using I2-tests. Random effects models were determined for effect sizes as standardized mean differences (SMD). SYNTHESIS: Twenty-five studies were included in the review and 17 in the meta-analysis. Most of the studies (58%) showed a low risk of bias. People with PD exhibit a shorter step when landing after crossing an obstacle (SMD = -0.50 [-0.69 to -0.31]). Compared to people without PD, people with PD also widen their support base (SMD = 0.27 [0.07-0.47]) and reduce gait velocity (SMD = -0.60 [-0.80 to -0.39]) when crossing the obstacle. CONCLUSIONS: People with PD adopt a more conservative motor behavior during obstacle crossing than those without PD, with a shorter step length when landing after crossing an obstacle, greater step width and lower crossing speed.

Arm swing asymmetry in people with Parkinson's disease and its relationship with gait: A systematic review and meta-analysis.

BACKGROUND: Individuals with Parkinson's disease present arm swing alterations that can adversely affect their locomotion. OBJECTIVE: To identify differences in arm swing asymmetry (ASA) between individuals with Parkinson's disease (PD) and healthy individuals and to investigate the relationship between ASA, temporal-spatial gait parameters, and disease progression. METHODS: A literature search was conducted in PubMed, Scopus, ProQuest, Web of Science, and EBSCOhost up to February 2023. Cross-sectional studies evaluating parameters of arm swing (AS) and ASA were included. Methodological quality was assessed using the Critical Appraisal Checklist, and the quality of the evidence was measured with a modified Grading of Recommendations Assessment, Development, and Evaluation. RESULTS: Fourteen studies were included in the systematic review (1130 participants). Irrespective of the medication phase (ON or OFF) and the type of walk test employed, the meta-analysis showed moderate-quality evidence that individuals with PD have increased ASA amplitude (SMD = 0.84; 95% CI: 0.69, 0.99; I²= 0%).Very low-quality evidence suggests higher ASA velocity (SMD=0.64; 95% CI: 0.24, 1.05; I²=59%) and lower AS amplitude on both the most affected (ES = -1.99, 95% CI: -3.04, -0.94, I2: 91%) and the least affected sides (ES = -0.75, 95% CI: -1.05, -0.44; I²=66%). Meta-regression indicated that ASA is inversely related to disease duration (Z: -2.4892, P< 0.05) and motor symptoms progression (Z: -2.1336, P< 0.05). CONCLUSIONS: Regardless of the medication phase and the type of walk test employed, individuals with PD exhibited greater ASA and decreased AS amplitude than healthy individuals. ASA decreases as the disease progresses and symptoms worsen.

Sprint exercise for subjects with mild-to-moderate Parkinson's disease: Feasibility and biomechanical outputs.

BACKGROUND: High-intensity training, a still unexplored exercise for individuals with Parkinson's disease, is positively related with increased functionality and aerobic profile in healthy individuals. The aim of this work was to evaluate the feasibility, safety, and acceptance of sprint running in individuals with mild-to-moderate Parkinson's. Additionally, we compared sprint biomechanical outputs of force, velocity and power between individuals with Parkinson's disease and healthy. METHODS: Physically trained subjects with Parkinson's, men, (n = 16, 64:9.01 years, stage between 1 and 3 in the Hoehn and Yahr, 16.8:7.1 at Unified Parkinson's disease Rating Scales, and control group (n = 21, 65:9.27 years) performed 20 m sprint sessions. We analyzed the self-reported satisfaction and acceptance using a self-administered questionnaire, and the sprint biomechanics and performance based on high-speed video recordings. FINDINGS: All participants completed the tests with high feasibility, acceptability and satisfaction scores. The sprint maximal force and maximal power outputs were higher in Parkinson's disease. Conversely, control group showed higher mechanical effectiveness values. Interestingly, no difference in velocity capabilities and overall 20-m sprint performance was observed between groups, possibly explained by different mechanical strategies in both groups over the sprint accelerations. Linear regression analyses showed that physical qualities are predictors of mechanical effectiveness, and mechanical variables are important determinants of sprint performance on Parkinson's disease. INTERPRETATION: Sprint is a feasible exercise for people with mild-to-moderate Parkinson's disease. Even though differences in physical qualities and mechanical effectiveness exist between subjects with Parkinson's disease and healthy, there is no overall substantial impact on sprint running performance.

Can We Rely on Mobile Devices and Other Gadgets to Assess the Postural Balance of Healthy Individuals? A Systematic Review.

The consequences of falls, costs, and complexity of conventional evaluation protocols have motivated researchers to develop more effective balance assessments tools. Healthcare practitioners are incorporating the use of mobile phones and other gadgets (smartphones and tablets) to enhance accessibility in balance evaluations with reasonable sensitivity and good cost-benefit. The prospects are evident, as well as the need to identify weakness and highlight the strengths of the different approaches. In order to verify if mobile devices and other gadgets are able to assess balance, four electronic databases were searched from their inception to February 2019. Studies reporting the use of inertial sensors on mobile and other gadgets to assess balance in healthy adults, compared to other evaluation methods were included. The quality of the nine studies selected was assessed and the current protocols often used were summarized. Most studies did not provide enough information about their assessment protocols, limiting the reproducibility and the reliability of the results. Data gathered from the studies did not allow us to conclude if mobile devices and other gadgets have discriminatory power (accuracy) to assess postural balance. Although the approach is promising, the overall quality of the available studies is low to moderate.

The Effects of Hydrotherapy on Balance, Functional Mobility, Motor Status, and Quality of Life in Patients with Parkinson Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Individuals with Parkinson disease (PD) present balance and functional mobility disabilities that negatively affect the quality of life (QOL). OBJECTIVE: To systematically review the effects of hydrotherapy on balance, functional mobility, QOL, and motor status in patients with PD. DESIGN: Systematic review and meta-analysis. PARTICIPANTS: A total of 484 participants were included. The mean age of participants ranged from 54 to 78 years. The average duration of PD ranged from 3 to 10 years. METHODS: MEDLINE (PubMed), Embase, Cochrane CENTRAL, SCOPUS, Scielo, Physiotherapy Evidence Database (PEDro), and Google Scholar were searched from inception to December 2017. Randomized controlled trials (RCT), non-RCT, and pre-post studies were included. MAIN OUTCOME MEASUREMENTS: Berg Balance Scale; Timed Up and Go test; Parkinson's disease quality of life and Short Form-36 Health Survey; Unified Parkinson Disease Rating Scale-Part III. RESULTS: A total of 19 studies were identified, including eight RCTs, three non-RCTs, and eight pre-post studies. Our meta-analysis showed a moderate quality of evidence for positive effects of hydrotherapy combined or not with land-based therapy on balance (133 patients; MD = 2.00 [95% CI, 0.56 to 3.43; I2 0%, P = .01]) and functional mobility (133 patients; MD = -1.08 [95% CI, -1.99 to -0.18; I2 8%, P = .02]). However, hydrotherapy combined or not with land-based therapy did not improve QOL (76 patients; MD = -6.35 [95% CI, -13.04 to 0.33; I2 7%, P = .06]) and motor status (140 patients; MD = -1.11 [95% CI, -3.27 to 1.04; I2 0%, P = .31). The risk of bias across the included RCTs was low. CONCLUSIONS: Hydrotherapy, combined or not with other therapies, may improve balance and functional mobility of patients with PD when compared to land-based therapy alone or usual care. LEVEL OF EVIDENCE: Level I.

Noninvasive Brain Stimulation Improves Hemispatial Neglect After Stroke: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the effectiveness of noninvasive brain stimulation (NIBS)-repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS)-on hemispatial neglect and performance in activities of daily living (ADL) after stroke. DATA SOURCES: MEDLINE (PubMed), EMBASE, Cochrane CENTRAL, Scopus, SciELO, and Physiotherapy Evidence Database were searched from database inception to December 2016. DATA SELECTION: Randomized controlled trials or crossover trials focused on determining the effects of tDCS or rTMS combined or not combined with other therapies for hemispatial neglect after stroke. DATA EXTRACTION: Methodological characteristics of the studies, number of participants, comparison groups, interventions, and outcomes were extracted. DATA SYNTHESIS: Ten trials comprising 226 participants had data that were suitable for the meta-analysis. Meta-analysis showed that NIBS combined with other therapies significantly improves hemispatial neglect (standardized mean difference [SMD]=-1.91; 95% confidence interval [CI], -2.57 to -1.25; I2=71%). A sensitivity analysis showed that rTMS (SMD=-2.16; 95% CI, -3.00 to -1.33; I2=76%) and tDCS (SMD=-1.07; 95% CI, -1.76 to -0.37; I2=0%) had positive effects on hemispatial neglect. Furthermore, both excitatory (SMD=-2.34; 95% CI, -3.56 to -1.12; I2=65%) and inhibitory (SMD=-1.69; 95% CI, -2.49 to -0.88; I2=75%) stimulations were effective. CONCLUSIONS: This meta-analysis reveals moderate-quality evidence for the effectiveness of NIBS protocols combined with other therapies on hemispatial neglect and performance in ADL after stroke.

Analyzing gait variability and dual-task interference in patients with Parkinson's disease and freezing by means of the word-color Stroop test.

The ability to carry out two tasks at once is critical to effective functioning in the real world and deficits are termed Dual-task interference or effect-DTE. DTE substantially compromised the gait of subjects with Parkinson's disease and freezing of gait (PD + FOG), leading to exaggerated slowing, increasing gait dysrhythmicity, and inducing FOG episodes. This study aimed to investigate the DTE in gait variability of subjects with PD and freezing of gait (PD + FOG). Thirty-three patients with PD + FOG and 14 healthy individuals (REFERENCE) took part at this study. Two gait conditions were analyzed: usual walking (single task) and walking while taking the word-color Stroop test (dual task). The computed variables were as follows: gait velocity, step length, step timing, gait asymmetry, variability measures and DTE of each variable. The PD + FOG group has presented negative DTE values for all analyzed variables, indicating dual task cost. The REFERENCE group has presented dual-task benefits for step length standard deviation and step time. Differences between both groups and conditions were found for all variables, except for step time. Taking the word-color Stroop test while walking led to a larger dual-task cost in subjects with PD + FOG.

Effects of functional and analytical strength training on upper-extremity activity after stroke: a randomized controlled trial

ABSTRACT Objective To investigate the effects of functional strengthening (using functional movements) and analytical strengthening (using repetitive movements) on level of activity and muscular strength gain in patients with chronic hemiparesis after stroke. Method A randomized, assessor-blinded trial was conducted in a therapist-supervised home rehabilitation program. Twenty-seven patients with chronic stroke were randomly allocated one of two groups: functional strengthening (FS) (n=13) and analytical strengthening (AS) (n=14). Each group received a five-week muscle strengthening protocol (30 minutes per day, three times per week) including functional movements or analytical movements, respectively. Pre-, post-, and ten-month follow-up outcomes included the Upper-Extremity Performance Test (primary outcome), Shoulder and Grip Strength, Active Shoulder Range of Motion (ROM), the Fugl-Meyer Assessment, and the Modified Ashworth Scale (MAS) (secondary outcomes). Results There was significant improvement in the Upper-Extremity Performance Test for the combined unilateral and bilateral task scores in the FS Group (mean difference 2.4; 95% CI=0.14 to 4.6) in the 10-month follow-up. No significant difference was observed between groups in the other outcomes (p>0.05). Conclusion A five-week home-based functional muscle strengthening induced positive results for the upper-extremity level of activity of patients with moderate impairment after chronic stroke.

Effects of functional and analytical strength training on upper-extremity activity after stroke: a randomized controlled trial.

Objective: To investigate the effects of functional strengthening (using functional movements) and analytical strengthening (using repetitive movements) on level of activity and muscular strength gain in patients with chronic hemiparesis after stroke. Method: A randomized, assessor-blinded trial was conducted in a therapist-supervised home rehabilitation program. Twenty-seven patients with chronic stroke were randomly allocated one of two groups: functional strengthening (FS) (n=13) and analytical strengthening (AS) (n=14). Each group received a five-week muscle strengthening protocol (30 minutes per day, three times per week) including functional movements or analytical movements, respectively. Pre-, post-, and ten-month follow-up outcomes included the Upper-Extremity Performance Test (primary outcome), Shoulder and Grip Strength, Active Shoulder Range of Motion (ROM), the Fugl-Meyer Assessment, and the Modified Ashworth Scale (MAS) (secondary outcomes). Results: There was significant improvement in the Upper-Extremity Performance Test for the combined unilateral and bilateral task scores in the FS Group (mean difference 2.4; 95% CI=0.14 to 4.6) in the 10-month follow-up. No significant difference was observed between groups in the other outcomes (p>0.05). Conclusion: A five-week home-based functional muscle strengthening induced positive results for the upper-extremity level of activity of patients with moderate impairment after chronic stroke.

Humeral external rotation handling by using the Bobath concept approach affects trunk extensor muscles electromyography in children with cerebral palsy.

This study aimed to investigate the electromyographic activity of cervical and trunk extensors muscles in children with cerebral palsy during two handlings according to the Bobath concept. A crossover trial involving 40 spastic diplegic children was conducted. Electromyography (EMG) was used to measure muscular activity at sitting position (SP), during shoulder internal rotation (IR) and shoulder external rotation (ER) handlings, which were performed using the elbow joint as key point of control. Muscle recordings were performed at the fourth cervical (C4) and at the tenth thoracic (T10) vertebral levels. The Gross Motor Function Classification System (GMFCS) was used to assess whether muscle activity would vary according to different levels of severity. Humeral ER handling induced an increase on EMG signal of trunk extensor muscles at the C4 (P=0.007) and T10 (P<0.001) vertebral levels. No significant effects were observed between SP and humeral IR handling at C4 level; However at T10 region, humeral IR handling induced an increase of EMG signal (P=0.019). Humeral ER resulted in an increase of EMG signal at both levels, suggesting increase of extensor muscle activation. Furthermore, the humeral ER handling caused different responses on EMG signal at T10 vertebra level, according to the GMFCS classification (P=0.017). In summary, an increase of EMG signal was observed during ER handling in both evaluated levels, suggesting an increase of muscle activation. These results indicate that humeral ER handling can be used for diplegic CP children rehabilitation to facilitate cervical and trunk extensor muscles activity in a GMFCS level-dependent manner.

Effect of prior exercise training and myocardial infarction-induced heart failure on the neuronal and glial densities and the GFAP-immunoreactivity in the posterodorsal medial amygdala of rats.

Exercise training has neuroprotective effects whereas myocardial infarction (MI) and heart failure (HF) can cause neuronal death and reactive gliosis in the whole amygdala. The posterodorsal medial amygdala (MePD) is involved with cardiovascular reflexes and the central control of sympathetic/parasympathetic responses. Our aim was to study the effects of prior exercise training and of MI-induced HF on the neuronal and glial densities and the glial fibrillary acidic protein-immunoreactivity (GFAP-ir) in the MePD of adult male rats. Animals (n= 5/group) were: control, sedentary submitted to a sham MI (Sed Sham), sedentary submitted to MI/HF (Sed HF), trained on a treadmill and submitted to a sham MI (T Sham) or trained on a treadmill and submitted to MI/HF (T HF). The number of neurons and glial cells in the MePD was estimated using the optical fractionator and the GFAP-ir was quantified by optical densitometry. In the respective groups, treadmill training improved physical performance and MI damaged near 40% of the left ventricle. There was a hemispheric lateralization effect on the density of neurons (higher in the right MePD), but no significant difference in either the neuronal or the glial densities due to experimental condition. Regional GFAP-ir results revealed that the Sed HF group had a higher expression in the left MePD compared to the control and the Sed Sham rats (p⟨0.01). The present data did not evidence the effects of training or MI/HF in the MePD cellular density, but indicate a possible local restructuring of astrocytic cytoskeleton after MI/HF in rats.

Coumestrol treatment prevents Na+, K+ -ATPase inhibition and affords histological neuroprotection to male rats receiving cerebral global ischemia.

OBJECTIVE: In this study, we investigated the possible mechanisms underlying the neuroprotective effects of coumestrol, a potent isoflavonoid with antioxidant activities and binding affinities for both estrogen receptors (ER) ER-alpha and ER-beta that are comparable to those of 17beta-estradiol, in a model of global ischemia in male subjects. METHODS: Wistar rats underwent global ischemia (10 minutes) or sham surgery and received a single intracerebroventricular (icv) infusion of 20 µg of coumestrol or vehicle 1 hour before ischemia or 0, 3, 6, or 24 hours after reperfusion. RESULTS: The data analysis revealed an extensive neuronal death in the CA1 hippocampal subfield at 7 days, and a significant decrease in the Na+, K+ -ATPase activity at 1 and 24 hours after ischemia, and both injuries were attenuated by coumestrol administration. CONCLUSIONS: Coumestrol treatment was effective in preventing neuronal loss in all times of administration as well as able to rescue the Na+, K+ -ATPase activity, suggesting its potential benefits for either prevention or therapeutics use against cerebral ischemia in males.

Coumestrol has neuroprotective effects before and after global cerebral ischemia in female rats.

Global ischemia arising during cardiac arrest or cardiac surgery causes highly selective, delayed death of hippocampal CA1 neurons. Phytoestrogens are naturally occurring plant-derived compounds that are present in the human diet and are considered selective estrogen receptor (ER) modulators. The phytoestrogen coumestrol is a potent isoflavonoid, with binding affinities for both ER-α and ER-ß that are comparable to those of 17 b-estradiol. The present study examined the hypothesis that coumestrol protects hippocampal neurons in ovariectomized rats in a model of cerebral global ischemia. Ovariectomized rats were subjected to global ischemia (10 min) or sham surgery and received a single intracerebroventricular or peripheral infusion of 20 µg of coumestrol, 20 µg of estradiol or vehicle 1h before ischemia or 0 h, 3h, 6h or 24h after reperfusion. Estradiol and coumestrol afforded significant neuroprotection in all times of administration, with the exception of estradiol given 24h after the ischemic insult. Animals received icv infusion of the broad-spectrum ER antagonist ICI 182,780 (50 µg) or vehicle into the lateral ventricle just before the E2 or coumestrol administration. The ER antagonist abolished estradiol protection, consistent with a role of classical ERs. In contrast, ICI 182,780 effected only partial reversal of the neuroprotective actions of coumestrol, suggesting that other cellular mediators in addition to classical ERs may be important. Additional research is needed to determine the molecular targets mediating the neuroprotective action of coumestrol and the therapeutic potential of this phytoestrogen in the mature nervous system.

Resveratrol prevents CA1 neurons against ischemic injury by parallel modulation of both GSK-3ß and CREB through PI3-K/Akt pathways.

Accumulating evidence indicates that resveratrol potently protects against cerebral ischemia damage due to its oxygen free radicals scavenging and antioxidant properties. However, cellular mechanisms that may underlie the neuroprotective effects of resveratrol in brain ischemia are not fully understood yet. This study aimed to investigate the potential association between the neuroprotective effect of resveratrol and the apoptosis/survival signaling pathways, in particular the glycogen synthase kinase 3 (GSK-3ß) and cAMP response element-binding protein (CREB) through phosphatidylinositol 3-kinase (PI3-K)-dependent pathway. An experimental model of global cerebral ischemia was induced in rats by the four-vessel occlusion method for 10 min and followed by different periods of reperfusion. Nissl staining indicated extensive neuronal death at 7 days after ischemia/reperfusion. Administration of resveratrol by i.p. injections (30 mg/kg) for 7 days before ischemia significantly attenuated neuronal death. Both GSK-3ß and CREB appear to play a critical role in resveratrol neuroprotection through the PI3-K/Akt pathway, as resveratrol pretreatment increased the phosphorylation of Akt, GSK-3ß and CREB in 1 h in the CA1 hippocampus after ischemia/reperfusion. Furthermore, administration of LY294002, an inhibitor of PI3-K, compromised the neuroprotective effect of resveratrol and decreased the level of p-Akt, p-GSK-3ß and p-CREB after ischemic injury. Taken together, the results suggest that resveratrol protects against delayed neuronal death in the hippocampal CA1 by maintaining the pro-survival states of Akt, GSK-3ß and CREB pathways. These data suggest that the neuroprotective effect of resveratrol may be mediated through activation of the PI3-K/Akt signaling pathway, subsequently downregulating expression of GSK-3ß and CREB, thereby leading to prevention of neuronal death after brain ischemia in rats.

Resveratrol preconditioning modulates inflammatory response in the rat hippocampus following global cerebral ischemia.

Considerable evidence has been accumulated to suggests that blocking the inflammatory reaction promotes neuroprotection and shows therapeutic potential for clinical treatment of ischemic brain injury. Consequently, anti-inflammatory therapies are being explored for prevention and treatment of these diseases. Induction of brain tolerance against ischemia by pretreatment with resveratrol has been found to influence expression of different molecules. It remains unclear, however, whether and how resveratrol preconditioning changes expression of inflammatory mediators after subsequent global cerebral ischemia/reperfusion (I/R). Therefore, we investigated the effect of resveratrol pretreatment on NF-κB inflammatory cascade, COX-2, iNOS and JNK levels in experimental I/R. Adult male rats were subjected to 10 min of four-vessel occlusion and sacrificed at selected post-ischemic time points. Resveratrol (30 mg/kg) pretreatment was injected intraperitoneally 7 days prior to I/R induction. We found that resveratrol treatment before insult remarkably reduced astroglial and microglial activation at 7 days after I/R. It greatly attenuated I/R-induced NF-κB and JNK activation with decreased COX-2 and iNOS production. In conclusion, the neuroprotection of resveratrol preconditioning may be due in part to the suppression of the inflammatory response via regulation of NF-κB, COX-2 and iNOS induced by I/R. JNK was also suggested to play a protective role through in neuroprotection of resveratrol, which may also be contributing to reduction in neuroinflammation. The study adds to a growing literature that resveratrol can have important anti-inflammatory actions in the brain.

Pro-angiogenic effects of resveratrol in brain endothelial cells: nitric oxide-mediated regulation of vascular endothelial growth factor and metalloproteinases.

Resveratrol may be a powerful way of protecting the brain against a wide variety of stress and injury. Recently, it has been proposed that resveratrol not only reduces brain injury but also promotes recovery after stroke. But the underlying mechanisms are unclear. Here, we tested the hypothesis that resveratrol promotes angiogenesis in cerebral endothelial cells and dissected the signaling pathways involved. Treatment of cerebral endothelial cells with resveratrol promoted proliferation, migration, and tube formation in Matrigel assays. Consistent with these pro-angiogenic responses, resveratrol altered endothelial morphology resulting in cytoskeletal rearrangements of ß-catenin and VE-cadherin. These effects of resveratrol were accompanied by activation of phosphoinositide 3 kinase (PI3-K)/Akt and Mitogen-Activated Protein Kinase (MAPK)/ERK signaling pathways that led to endothelial nitric oxide synthase upregulation and increased nitric oxide (NO) levels. Subsequently, elevated NO signaling increased vascular endothelial growth factor and matrix metalloproteinase levels. Sequential blockade of these signaling steps prevented resveratrol-induced angiogenesis in cerebral endothelial cells. These findings provide a mechanistic basis for the potential use of resveratrol as a candidate therapy to promote angiogenesis and neurovascular recovery after stroke.

Chronic brain hypoperfusion causes early glial activation and neuronal death, and subsequent long-term memory impairment.

Reduction of cerebral blood flow is an important risk factor for dementia states and other brain dysfunctions. In present study, the effects of permanent occlusion of common carotid arteries (2VO), a well established experimental model of brain ischemia, on memory function were investigated, as assessed by reference and working spatial memory protocols and the object recognition task; cell damage to the hippocampus, as measured through changes in immunoreactivity for GFAP and the neuronal marker NeuN was also studied. The working hypothesis is that metabolic impairment following hypoperfusion will affect neuron and glial function and result in functional damage. Adult male Wistar rats were submitted to the modified 2VO method, with the right common carotid artery being occluded first and the left one week later, and tested seven days, three and six months after the ischemic event. A significant cognitive deficit was found in both reference and working spatial memory, as well as in the object recognition task, three and six months after surgery. Neuronal death and reactive astrogliosis were already present at 7 days and continued for up to 3 months after the occlusion; interestingly, there was no significant reduction in hippocampal volume. Present data suggests that cognitive impairment caused by brain hypoperfusion is long - lasting and persists beyond the time point of recovery from glial activation and neuronal loss.