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Oxylipins and fatty acids may be novel therapeutic targets for cardiovascular disease. The objective was to determine if plasma oxylipins or fatty acids can influence the odds of cardiovascular/cerebrovascular events. In 98 patients (25 female, 73 male) with peripheral artery disease, the prevalence of transient ischemic attacks, cerebrovascular accidents, stable angina, and acute coronary syndrome was n = 16, 10, 16, and 24, respectively. Risk factors such as being male, diagnosed hypertension, diabetes mellitus, and hyperlipidemia were not associated with events. Plasma fatty acids and oxylipins were analyzed with gas chromatography and HPLC-MS/MS, respectively. None of 24 fatty acids quantified were associated with events. In contrast, 39 plasma oxylipins were quantified, and 8 were significantly associated with events. These 8 oxylipins are known regulators of vascular tone. For example, every 1 unit increase in Thromboxane B2/Prostaglandin F1α and every 1 nmol/L increase in plasma 16-hydroxyeicosatetraenoic acid, thromboxane B2, or 11,12-dihydroxyeicosatrienoic acid (DiHETrE) increased the odds of having had ≥2 events versus no event ( p < 0.05). The greatest predictor was plasma 8,9-DiHETrE, which increased the odds of acute coronary syndrome by 92-fold. In conclusion, specific oxylipins were highly associated with clinical events and may represent specific biomarkers and (or) therapeutic targets of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Stroke is a common cerebrovascular disease in aging populations, and constitutes the second highest principle cause of mortality and the principle cause of permanent disability, and ischemic stroke is the primary form. Osthole is a coumarin derivative extracted from the fruits of Cnidium monnieri (L.) Cusson. In this study, we established a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) in vivo and found that MCAO/R caused cerebral infarction, hippocampus neuronal injury and apoptosis, and also activated the Notch 1 signaling pathway. However, treatment with osthole further enhanced the activity of Notch 1 signaling and reduced the cerebral infarction as well as the hippocampus neuronal injury and apoptosis induced by MCAO/R in a dose-dependent manner. The same results were observed in a primary neuronal oxygen glucose deficiency/reperfusion (OGD/R) model in vitro, and the effect of osthole could be blocked by an inhibitor of Notch 1 signaling, N-[ N-(3,5-difluorophenacetyl)- l-alanyl]- S-phenylglycine tert-butyl ester (DAPT). Therefore, we demonstrated that osthole injection prevented rat ischemia-reperfusion injury via activating the Notch 1 signaling pathway in vivo and in vitro in a dose-dependent manner, which may be significant for clinical treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

Stroke is a pathologic condition associated with redox imbalance. This pilot study was designed to evaluate the effect of the consumption of the nutritional supplement ALAnerv on some oxidative stress markers in postacute stroke patients undergoing rehabilitation. To achieve this goal, we assigned 28 patients to 2 study groups: (−)ALA and (+)ALA. Patients in both groups participated in the same rehabilitation program and received comparable standard medications; however, patients in the (+)ALA group received ALAnerv for 2 weeks (2 pills per day). We assessed total and nonproteic thiols, protein carbonyls, ceruloplasmin, oxidized low-density lipoprotein (LDL) particles, lipid hydroperoxide concentrations, gamma-glutamyl transpeptidase activity, and total antioxidant capacity. Regression analysis indicated that supplementation with ALAnerv was responsible for the significant decrease in glucose ( p = 0.002) and oxidized LDL particles ( p < 0.001) during the study period. For both parameters, the variation in the percent of concentration between the 2 groups during the study period reached statistical significance ( p = 0.012 and p < 0.001, respectively). Moreover, Barthel Index values at discharge were significantly influenced by ALAnerv treatment. These preliminary results indicate that ALAnerv might be helpful because it rapidly corrects plasma fasting glucose and corrects serum oxidized LDL particle concentrations, suggesting the need for longer treatment with 2 pills or more per day. [ABSTRACT FROM AUTHOR]

A major cause of stroke is cerebral ischemia in regions supplied by the middle cerebral artery (MCA). In this study, we hypothesized that compromised cardiovascular function during static exercise may involve altered expression of inducible NOS (iNOS) protein within the rostral ventrolateral medulla (RVLM) and caudal ventrolateral medulla (CVLM). We compared cardiovascular responses and iNOS protein expression within the left and right sides of both RVLM and CVLM in sham-operated rats and in rats with a 90 min left-sided MCA occlusion (MCAO) followed by 24 h of reperfusion. Increases in blood pressure during a static muscle contraction were attenuated in MCAO rats compared with sham-operated rats. Also, iNOS expression within the left RVLM was augmented compared with the right RVLM in MCAO rats and compared with both RVLM quadrants in sham-operated rats. In contrast, compared with sham-operated rats and the right CVLM of MCAO rats, iNOS expression was attenuated in the left CVLM in left-sided MCAO rats. These data suggest that the attenuation of pressor responses during static exercise in MCAO rats involves overexpression of iNOS within the ipsilateral RVLM and attenuation in iNOS within the ipsilateral CVLM. Differential expression of iNOS within the medulla plays a role in mediating cardiovascular responses during static exercise following stroke. [ABSTRACT FROM AUTHOR]

The precise role of microglia in stroke and cerebral ischemia has been the subject of debate for a number of years. Microglia are capable of synthesizing numerous soluble and membrane-bound biomolecules, some known to be neuroprotective, some neurotoxic, whereas others have less definitive bioactivities. The molecular mechanisms through which microglia activate these molecules have thus become an important area of ischemia research. Here we provide a survey review that summarizes the key actions of microglial factors in cerebral ischemia including complement proteins, chemokines, pro-inflammatory cytokines, neurotrophic factors, hormones, and proteinases, as well several important messenger molecules that play a part in how these factors respond to extracellular signals during ischemic injuries. We also provide some new perspectives on how microglial intracellular signaling may contribute to the seemingly contradictory roles of several microglial effector molecules. [ABSTRACT FROM AUTHOR]

There are indications that both intensive exercise and electrical stimulation have a beneficial effect on arm function in post-stroke hemiplegic patients. We recommend the use of Functional Electrical Therapy (FET), which combines electrical stimulation of the paretic arm and intensive voluntary movement of the arm to exercise daily functions. FET was applied 30 min daily for 3 weeks. Forty-one acute hemiplegics volunteered in the 18-months single blinded cross-over study (CoS). Nineteen patients (Group A) participated in FET during their acute hemiplegia, and 22 patients (Group B) participated in FET during their chronic phase of hemiplegia. Group B patients were controls during FET in acute hemiplegia, and Group A patients were controls during the FET in chronic hemiplegia. Thirty-two patients completed the study. The outcomes of the Upper Extremity Function Test (UEFT) were used to assess the ability of patients to functionally use objects, as were the Drawing Test (DT) (used to assesse the coordination of the arm), the Modified Ashworth Scale, the range of movement, and the questionnaire estimating the patients' satisfaction with the usage of the paretic arm. Patients who participated in the FET during the acute phase of hemiplegia (Group A) reached functionality of the paretic arm, on average, in less than 6 weeks, and maintained this near-normal use of the arm and hand throughout the follow-up. The gains in all outcome scores were significantly larger in Group A after FET and at all follow-ups compared with the scores before the treatment. The gains in patients who participated in the FET in the chronic phase of hemiplegia (Group B) were measurable, yet not significant. The speed of recovery was larger during the period of the FET compared with the follow-up period. The gains in Group A were significantly larger compared with the gains in Group B. The FET greatly promotes the recovery of the paretic arm if applied during the acute phase of post-stroke hemiplegia. [ABSTRACT FROM AUTHOR]

This paper presents a case study that tested the feasibility and efficacy of using injectable microstimulators (BIONs®) in a functional electrical stimulation (FES) device to correct foot drop. Compared with surface stimulation of the common peroneal nerve, stimulation with BIONs provides more selective activation of specific muscles. For example, stimulation of the tibialis anterior (TA) and extensor digitorum longus (EDL) muscles with BIONs produces ankle flexion without excessive inversion or eversion of the foot (i.e., balanced flexion). Efficacy was assessed using a 3-dimensional motion analysis of the ankle and foot trajectories during walking with and without stimulation. Without stimulation, the toe on the affected leg drags across the ground. BION stimulation of the TA muscle and deep peroneal nerve (which innervates TA and EDL) elevates the foot such that the toe clears the ground by 3 cm, which is equivalent to the toe clearance in the less affected leg. The physiological cost index (PCI) measured effort during walking. The PCI equals the change in heart rate (from rest to activity) divided by the walking speed; units are beats per metre. The PCI is high without stimulation (2.29 ± 0.37, mean ± SD) and greatly reduced with surface (1.29 ± 0.10) and BIONic stimulation (1.46 ± 0.24). Also, walking speed increased from 9.4 ± 0.4 m/min without stimulation to 19.6 ± 2.0 m/min with surface and 17.8 ± 0.7 m/min with BIONic stimulation. These results suggest that FES delivered by a BION is an alternative to surface stimulation and provides selective control of muscle activation. [ABSTRACT FROM AUTHOR]

Constraint-induced movement therapy (CIMT), which involves restraint of the nonimpaired arm coupled with physiotherapy for the impaired arm, lessens impairment and disability in stroke patients. Surprisingly, immediate ipsilateral forelimb immobilization exacerbates brain injury in rats. We tested whether immediate ipsilateral restraint for 7 days aggravates injury after a devascularization lesion in rats. Furthermore, we hypothesized that ipsilateral restraint aggravates injury by causing hyperthermia. In experiment 1, each rat received two lesions, one in the motor cortex and one in the visual cortex. Ipsilateral restraint increased only the motor cortex lesion. In additional rats, no differences in core temperature occurred after ipsilateral or contralateral restraint. Thus, ipsilateral restraint does not aggravate injury by a systemic side effect. In experiment 2, we hypothesized that ipsilateral restraint causes hyperthermia in the region surrounding the initial cortical lesion. Brain temperature, measured via telemetry, was significantly higher (~1 °C for 24 h) with ipsilateral restraint. A third experiment similarly found that ipsilateral restraint aggravates injury and causes local cortical hyperthermia and that contralateral restraint with externally induced mild hyperthermia aggravates injury. In conclusion, immediate ipsilateral restraint aggravates injury apparently by localized events that include hyperthermia. Caution must be exercised in applying early CIMT to humans, as hyperthermia is detrimental. [ABSTRACT FROM AUTHOR]

Transient or permanent focal brain injury following acute thromboembolic occlusion develops from a complex cascade of pathophysiological events. The processes of excitotoxicity, peri-infarct depolarisation, inflammation, and apoptosis within the ischemic penumbra are proposed. While the translation of therapeutic agents from the animal models to human clinical trials have been disappointing, there remains an atmosphere of optimism as a result of the development of new diagnostic and therapeutic approaches, which include physiological, as opposed to pharmacological, intervention. This article provides an insight into the understanding of cerebral ischemia, together with current and future treatment strategies.Key words: cerebral ischemia, stroke, pathophysiology.La lésion cérébrale focale permanente ou transitoire qui se produit après une occlusion thromboembolique aiguë se développe à partir d'une cascade complexe d'événements pathophysiologiques. Les processus d'excitotoxicité, de dépolarisation post-infarctus, d'inflammation et d'apoptose dans la pénombre ischémique sont mis en cause. Bien que le transfert d'agents thérapeutiques des modèles animaux aux essais cliniques humains ait donné des résultats décevants, la mise au point de nouvelles approches diagnostiques et thérapeutiques, comportant une intervention physiologique plutôt que pharmacologique, est encourageante. Le présent article donne un aperçu de la compréhension de l'ischémie cérébrale ainsi que des stratégies thérapeutiques actuelles et futures.Mots clés : ischémie cérébrale, accident vasculaire cérébral, pathophysiologie.[Traduit par la Rédaction] [ABSTRACT FROM AUTHOR]

Many diseases associated with ageing have an underlying oxidative stress and accompanying inflammatory component, for example, Alzheimer's disease or atherosclerosis. Reviewed in this manuscript are: the role of oxidative stress in activating the transcription factor nuclear factor kappa B (NFκB), the role of NFκB in activating pro-inflammatory gene transcription, strong oxidants produced by cells, anti-oxidant defense systems, the central role of phase 2 enzymes in the anti-oxidant defense, dietary phase 2 enzyme inducers and evidence that dietary phase 2 enzymes decrease oxidative stress. It is likely that a diet containing phase 2 enzyme inducers may ameliorate or even prevent diseases that have a prominent inflammatory component to them. Research should be directed into the potential therapeutic effects of dietary phase 2 enzyme inducers in ameliorating diseases with an underlying oxidative stress and inflammatory component to them.Key words: Alzheimer's disease, atherosclerosis, diet, glutathione, inflammation, stroke.Un grand nombre de maladies associées au vieillissement ont un stress oxydatif sous-jacent accompagné d'une composante inflammatoire, par exemple l'athérosclérose. Dans cet article, nous réviserons les thèmes suivants : le rôle du stress oxydatif dans l'activation de la transcription du facteur nucléaire kappa B (FNκB), le rôle du FNκB dans l'activation de la transcription des gènes pro-inflammatoires, les puissants oxydants produits par les cellules, les systèmes de défense antioxydants, le rôle central des enzymes de phase 2 dans la défense antioxydante, les inducteurs d'enzymes de phase 2 alimentaires et la mise en évidence de la diminution du stress oxydatif par les enzymes de phase 2 alimentaires. Il semble très possible qu'un régime contenant des inducteurs d'enzymes de phase 2 puissent diminuer les symptômes des maladies ou même prévenir les maladies ayant une forte composante inflammatoire. Nous suggérons d'orienter la recherche vers l'étude des effets thérapeutiques potentiels des inducteurs d'enzymes de phase 2 alimentaires sur la diminution des symptômes des maladies ayant un stress oxydatif sous-jacent accompagné d'une composante inflammatoire.Mots clés : maladie d'Alzheimer, athérosclérose, régime, glutathion, inflammation, accident vasculaire cérébral.[Traduit par la Rédaction] [ABSTRACT FROM AUTHOR]

Machine learning may improve use of observational data to understand the nutritional epidemiology of cardiovascular disease (CVD) through better modelling of non-linearity, non-additivity, and dietary complexity. Our objective was to develop machine learning prediction models for exploring how nutrients are related to CVD risk and to evaluate their predictive performance. We established a population-based cohort from the Canadian Community Health Survey and measured CVD incidence and mortality from 2004 to 2018 using administrative databases of national hospital discharges and deaths. Predictors included 61 nutrition variables and fourteen socioeconomic, demographic, psychological, and behavioural variables. Conditional inference forest models were interpreted and evaluated by permutation feature importance, accumulated local effects, and predictive discrimination and calibration. A total of 12 130 individuals were included in the study. Use of supplements, caffeine, and alcohol were the most important nutrition variables for prediction of CVD. Supplement use was associated with decreased risk, caffeine was associated with increasing risk, and alcohol had a u-shaped association with risk. The model had an out-of-sample c-statistic of 0.821 (95% confidence interval = 0.801-0.842). Exploratory findings included both known and novel associations and predictive performance was competitive, suggesting that further application of machine learning to nutritional epidemiology may help elucidate risks and improve predictive models. Novelty: Machine learning prediction models were developed for CVD using dietary data. Models were interpreted with interpretable machine learning techniques, revealing diverse associations between diet and CVD. Models achieved comparable or superior predictive performance to existing CVD risk prediction models.

Evidence suggests exercise is "good medicine" after stroke, yet consensus is lacking on the time to initiate, type, exertion level, and duration per session. It remains a challenge to identify outcome measures for stroke-exercise trials that are sufficiently sensitive to intervention parameters. Cerebrovascular assessments, namely cerebral blood flow and intracranial pulsatility, are herein discussed as examples of quantitative brain-specific measures that may be useful to monitor exercise-related brain changes and help to guide stroke rehabilitation interventions. Novelty: Cerebral blood flow and arterial stiffness are potential vascular targets for stroke exercise trials.

Protein-energy malnutrition (PEM) commonly arises after stroke. We investigated the effects of preventing PEM on spontaneous recovery of forelimb use, infarct size, and the acute phase response in the chronic post-stroke period. Male, adult, Sprague-Dawley rats were acclimatized to control diet (12.5% protein), tested for pre-stroke forelimb use symmetry in the cylinder test, and exposed to photothrombotic cortical stroke or sham surgery. Food intake was monitored daily, and body weight weekly. Forelimb use was tested on day 4 after surgery, before assignment to control diet or PEM (0.5% protein), with subsequent testing on days 16 and 29. Blood, brain, and liver were collected on day 30. The low protein diet resulted in PEM, measured by decreased body weight ( p < 0.001) and food intake ( p = 0.016) and increased liver lipid ( p < 0.001). Stroke ( p = 0.016) and PEM ( p = 0.001) independently elicited increases in serum α-2-macroglobulin concentration, whereas PEM alone decreased albumin ( p < 0.001). PEM reduced recovery of forelimb use symmetry during exploration on days 16 ( p = 0.024) and 29 ( p = 0.013) but did not influence infarct size ( p = 0.775). Stroke reduced reliance on the stroke-affected forelimb to initiate exploration up until day 29 ( p < 0.001); PEM had no influence ( p ≥ 0.463). Preventing post-stroke PEM appears to yield direct benefits for certain types of motor recovery. Novelty Preventing post-stroke malnutrition benefits certain types of motor recovery. An acute phase response may contribute to the poorer recovery with malnutrition.