Depth-Dependent Control in Vision-Sensor Space for Reconfigurable Parallel Manipulators.

In this paper, a control approach for reconfigurable parallel robots is designed. Based on it, controls in the vision-sensor, 3D and joint spaces are designed and implemented in target tracking tasks in a novel reconfigurable delta-type parallel robot. No a priori information about the target trajectory is required. Robot reconfiguration can be used to overcome some of the limitations of parallel robots like small relative workspace or multiple singularities, at the cost of increasing the complexity of the manipulator, making its control design even more challenging. No general control methodology exists for reconfigurable parallel robots. Tracking objects with unknown trajectories is a challenging task required in many applications. Sensor-based robot control has been actively used for this type of task. However, it cannot be straightforwardly extended to reconfigurable parallel manipulators. The developed vision-sensor space control is inspired by, and can be seen as an extension of, the Velocity Linear Camera Model-Camera Space Manipulation (VLCM-CSM) methodology. Several experiments were carried out on a reconfigurable delta-type parallel robot. An average positioning error of 0.6 mm was obtained for static objectives. Tracking errors of 2.5 mm, 3.9 mm and 11.5 mm were obtained for targets moving along a linear trajectory at speeds of 6.5, 9.3 and 12.7 cm/s, respectively. The control cycle time was 16 ms. These results validate the proposed approach and improve upon previous works for non-reconfigurable robots.

A Novel Velocity-Based Control in a Sensor Space for Parallel Manipulators.

It is a challenging task to track objects moving along an unknown trajectory. Conventional model-based controllers require detailed knowledge of a robot's kinematics and the target's trajectory. Tracking precision heavily relies on kinematics to infer the trajectory. Control implementation in parallel robots is especially difficult due to their complex kinematics. Vision-based controllers are robust to uncertainties of a robot's kinematic model since they can correct end-point trajectories as error estimates become available. Robustness is guaranteed by taking the vision sensor's model into account when designing the control law. All camera space manipulation (CSM) models in the literature are position-based, where the mapping between the end effector position in the Cartesian space and sensor space is established. Such models are not appropriate for tracking moving targets because the relationship between the target and the end effector is a fixed point. The present work builds upon the literature by presenting a novel CSM velocity-based control that establishes a relationship between a movable trajectory and the end effector position. Its efficacy is shown on a Delta-type parallel robot. Three types of experiments were performed: (a) static tracking (average error of 1.09 mm); (b) constant speed linear trajectory tracking-speeds of 7, 9.5, and 12 cm/s-(tracking errors of 8.89, 11.76, and 18.65 mm, respectively); (c) freehand trajectory tracking (max tracking errors of 11.79 mm during motion and max static positioning errors of 1.44 mm once the object stopped). The resulting control cycle time was 48 ms. The results obtained show a reduction in the tracking errors for this robot with respect to previously published control strategies.

Modeling the neuro-mechanics of human balance when recovering from a fall: a continuous-time approach.

BACKGROUND: Balance control deteriorates with age and nearly 30% of the elderly population in the United States reports stability problems. Postural stability is an integral task to daily living reliant upon the control of the ankle and hip. To this end, the estimation of joint parameters can be a useful tool when analyzing compensatory actions aimed at maintaining postural stability. METHODS: Using an analytical approach, this study expands on previous work and analyzes a two degrees of freedom human model. The first two modes of vibration of the system are represented by the neuro-mechanical parameters of a second-order, time-varying Kelvin-Voigt model actuated at the ankle and hip. The model is tested using a custom double inverted pendulum and healthy volunteers who were subjected to a positional step-like perturbation during quiet standing. An in silico sensitivity analysis of the influence of inertial parameters was also performed. RESULTS: The proposed method is able to correctly identify the time-varying visco-elastic parameters of of a double inverted pendulum. We show that that the parameter estimation method can be applied to standing humans. These results appear to identify a subject-independent strategy to control quiet standing that combines both the modulation of stiffness, and the use of an intermittent control. CONCLUSIONS: This paper presents the analysis of the non-linear system of differential equations representing the control of lumped muscle-tendon units. It utilizes motion capture measurements to obtain the estimates of the system's control parameters by constructing a simple time-dependent regressor for estimating the time-varying parameters of the control with a single perturbation. This work is a step forward into the understanding of the neuro-mechanical control parameters of human recovering from a fall. In previous literature, the analysis is either restricted to the first vibrational mode of an inverted-pendulum model or assumed to be time-invariant. The proposed method allows for the analysis of hip related movement for stability control and highlights the importance of core training.

RNA interference of NADPH-cytochrome P450 reductase increases susceptibilities to multiple acaricides in Tetranychus urticae.

The two-spotted spider mite, Tetranychus urticae, is a polyphagous pest feeding on over 1100 plant species, including numerous highly valued economic crops. The control of T. urticae largely depends on the use of acaricides, which leads to pervasive development of acaricide resistance. Cytochrome P450-mediated metabolic detoxification is one of the major mechanisms of acaricide resistance in T. urticae. NADPH-cytochrome P450 reductase (CPR) plays as a crucial co-factor protein that donates electron(s) to microsomal cytochrome P450s to complete their catalytic cycle. This study seeks to understand the involvement of CPR/P450 in acaricide resistance in T. urticae. The full-length cDNA sequence of T. urticae's CPR (TuCPR) was cloned and characterized. TuCPR was ubiquitously transcribed in different life stages of T. urticae and the highest transcription was observed in the nymph and adult stages. TuCPR was constitutively over-expressed in six acaricide resistant populations compared to a susceptible one. TuCPR transcriptional expression was also induced by multiple acaricides in a time-dependent manner. Down-regulation of TuCPR via RNA interference (RNAi) in T. urticae led to reduced enzymatic activities of TuCPR and cytochrome P450s, as well as a reduction of resistance to multiple acaricides, abamectin, bifenthrin, and fenpyroximate. The outcome of this study highlights CPR as a potential novel target for eco-friendly control of T. urticae and other related plant-feeding pests.

Ethnic and language influence on parents' perception of paediatric behaviour management techniques.

BACKGROUND: Parental preference for various behaviour management techniques (BMTs) used in paediatric dentistry has been shown to be influenced by many factors, including ethnicity. AIM: To measure parental acceptability of BMTs used in paediatric dentistry and how it is influenced by ethnicity and language. DESIGN: Parents of patients presenting to a paediatric dentistry residency clinic in Houston, Texas, USA or Medellín, Colombia watched ten video BMT vignettes and rated their acceptance on a visual analog scale (VAS). Participants were categorized into six groups based on language, ethnicity, and country of residence. RESULTS: Parental acceptance of BMTs was affected by language, ethnicity, and country of residence (P = 2.2 × 10-16 ). Ethnic groups in the USA had a mean overall acceptance rate of all BMTs. Colombians rated all BMTs less acceptable than the US cohorts (P < 0.05), with the exception of voice control, which Colombians rate less acceptable than English-speaking Caucasians and Spanish-speaking Hispanics in the USA (P < 0.05). The Colombian population were not accepting of conscious sedation, nitrous oxide, general anaesthesia, and protective stabilization. CONCLUSIONS: Parents from different ethnic groups express different preferences in BMTs. Parents continue to prefer noninvasive techniques over pharmacologic and advanced techniques, with the exception of voice control.

[Complex regional pain syndrome]. / Syndrome douloureux régional complexe.

The Complex Regional Pain Syndrome (previously algodystrophy) is a rare affliction that usually affects a distal extremity (hand, foot). It occurs most frequently within weeks following a traumatic injury or stroke. It is a syndromic entity whose diagnosis is based on precise criteria, known as the Budapest criteria, excluding any disease that better explains the symptoms. The treatment must be given early. Functional restoration (physiotherapy, occupational therapy) is at the heart of the treatment, along with psychoeducation. Inappropriate disuse and avoidance, often encountered, must be combated. Bisphosphonates or steroids are first-line drugs at early stages. The evolution is often long, but the prognosis is favorable in about 75 % of cases (≤ 1 year).

Le syndrome douloureux régional complexe (anciennement algodystrophie) est une affection rare qui touche préférentiellement une extrémité (main, pied). Il se développe le plus souvent dans les semaines qui suivent un traumatisme ou un accident vasculaire cérébral. Il s'agit d'une entité syndromique dont le diagnostic repose sur des critères précis, dits de Budapest, excluant toute atteinte expliquant mieux les symptômes. Le traitement doit être précoce. La restauration fonctionnelle en est le cœur (physiothérapie, ergothérapie), associée à une psychoéducation. L'immobilisation inappropriée et l'évitement, souvent rencontrés, doivent être combattus. Bisphosphonates ou corticoïdes sont les médicaments de premier choix des formes précoces. L'évolution est souvent longue, mais le pronostic favorable dans environ 75 % des cas (≤ 1 an).

The hidden side of infective endocarditis: Diagnostic and management of 500 consecutive cases in noncardiac surgery centers (2009-2018).

BACKGROUND: We aimed to describe infective endocarditis cases from noncardiac surgery centers, as current knowledge on infective endocarditis is derived mostly from cardiac surgery hospitals. METHODS: An observational retrospective study (2009-2018) was conducted in 9 noncardiac surgery hospitals in Central Catalonia. All adult patients diagnosed with definitive infective endocarditis were included. Transferred and nontransferred cohorts were compared, and a logistic regression model was used to ascertain the prognostic factors. RESULTS: Overall, 502 infective endocarditis episodes were included: 183 (36.5%) were transferred to the cardiac surgery center, whereas 319 were not, with (18.7%) and without (45%) surgical indications. Cardiac surgery was performed in 83% of transferred patients. In-hospital (14% vs 23%) and 1-year (20% vs 35%) mortality rates were significantly lower in transferred patients (P < .001). Among the patients not undergoing cardiac surgery despite an indication, 55 (54%) died within 1 year. The multivariate analysis identified the following independent predictive factors for in-hospital mortality: Staphylococcus aureus infective endocarditis (odds ratio: 1.93 [1.08, 3.47]), heart failure (odds ratio: 3.87 [2.28, 6.57]), central nervous system embolism (odds ratio: 2.95 [1.41, 5.14]), and Charlson score (odds ratio: 1.19 [1.09, 1.30]), whereas community acquisition (odds ratio: 0.52 [0.29, 0.93]), cardiac surgery (odds ratio: 0.42 [0.20, 0.87]), but not transfer (odds ratio: 1.23 [0.84, 3.95]) were identified as protective factors. One-year mortality was associated with S. aureus infective endocarditis (odds ratio: 1.82 [1.04, 3.18]), heart failure (odds ratio: 3.74 [2.27, 6.16]), and Charlson score (odds ratio: 1.23 [1.13, 1.33]), whereas cardiac surgery (odds ratio: 0.41 [0.21, 0.79]) was identified as a protective factor. CONCLUSION: Patients not transferred to a referral cardiac surgery center have a worse prognosis compared to those ultimately transferred, as cardiac surgery is associated with lower mortality rates.

Different Safety Pattern of an Inactivated SARS-CoV-2 Vaccine (CoronaVac®) According to Age Group in a Pediatric Population from 3 to 17 Years Old, in an Open-Label Study in Chile.

During the COVID-19 pandemic, the importance of vaccinating children against SARS-CoV-2 was rapidly established. This study describes the safety of CoronaVac® in children and adolescents between 3- and 17-years-old in a multicenter study in Chile with two vaccine doses in a 4-week interval. For all participants, immediate adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) were registered throughout the study. In the safety subgroup, AEs were recorded 28 days after each dose. COVID-19 surveillance was performed throughout the study. A total of 1139 individuals received the first and 1102 the second dose of CoronaVac®; 835 were in the safety subgroup. The first dose showed the highest number of AEs: up to 22.2% of participants reported any local and 17.1% systemic AE. AEs were more frequent in adolescents after the first dose, were transient, and mainly mild. Pain at the inoculation site was the most frequent AE for all ages. Fever was the most frequent systemic AE for 3-5 years old and headache in 6-17 years old. No SAEs or AESIs related to vaccination occurred. Most of the COVID-19 cases were mild and managed as outpatients. CoronaVac® was safe and well tolerated in children and adolescents, with different safety patterns according to age.

Inactivated Vaccine-Induced SARS-CoV-2 Variant-Specific Immunity in Children.

Multiple vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been evaluated in clinical trials. However, trials addressing the immune response in the pediatric population are scarce. The inactivated vaccine CoronaVac has been shown to be safe and immunogenic in a phase 1/2 clinical trial in a pediatric cohort in China. Here, we report interim safety and immunogenicity results of a phase 3 clinical trial for CoronaVac in healthy children and adolescents in Chile. Participants 3 to 17 years old received two doses of CoronaVac in a 4-week interval until 31 December 2021. Local and systemic adverse reactions were registered for volunteers who received one or two doses of CoronaVac. Whole-blood samples were collected from a subgroup of 148 participants for humoral and cellular immunity analyses. The main adverse reaction reported after the first and second doses was pain at the injection site. Four weeks after the second dose, an increase in neutralizing antibody titer was observed in subjects relative to their baseline visit. Similar results were found for activation of specific CD4+ T cells. Neutralizing antibodies were identified against the Delta and Omicron variants. However, these titers were lower than those for the D614G strain. Importantly, comparable CD4+ T cell responses were detected against these variants of concern. Therefore, CoronaVac is safe and immunogenic in subjects 3 to 17 years old, inducing neutralizing antibody secretion and activating CD4+ T cells against SARS-CoV-2 and its variants. (This study has been registered at ClinicalTrials.gov under no. NCT04992260.) IMPORTANCE This work evaluated the immune response induced by two doses of CoronaVac separated by 4 weeks in healthy children and adolescents in Chile. To date, few studies have described the effects of CoronaVac in the pediatric population. Therefore, it is essential to generate knowledge regarding the protection of vaccines in this population. Along these lines, we reported the anti-S humoral response and cellular immune response to several SARS-CoV-2 proteins that have been published and recently studied. Here, we show that a vaccination schedule consisting of two doses separated by 4 weeks induces the secretion of neutralizing antibodies against SARS-CoV-2. Furthermore, CoronaVac induces the activation of CD4+ T cells upon stimulation with peptides from the proteome of SARS-CoV-2. These results indicate that, even though the neutralizing antibody response induced by vaccination decreases against the Delta and Omicron variants, the cellular response against these variants is comparable to the response against the ancestral strain D614G, even being significantly higher against Omicron.

The Kapitza's Pendulum as a Concurrent Strategy for Maintaining Upright Posture.

A Kapitza's pendulum shows that it is possible to stabilize an inverted pendulum by making its base oscillate vertically. This action seems to introduce an inertial effect which will produce an attractor about the upright vertical position. This work shows that the upright posture of the trunk achieved while walking can be explained using a combination of a vertical oscillation and an angular stiffness regulation at the pelvis. This is shown with an estimated oscillation and stiffness obtained from video recordings of an unimpaired and a Parkinsoninan gaits. By simulating the dynamic model of the pendulum for a range of parameters, a series of stability conditions are found. They show that the introduction of the vertical oscillation results in a fast stabilization of the trunk and point to control strategies which rely on the system's dynamics.

Extra virgin olive oil improved body weight and insulin sensitivity in high fat diet-induced obese LDLr-/-.Leiden mice without attenuation of steatohepatitis.

Dietary fatty acids play a role in the pathogenesis of obesity-associated non-alcoholic fatty liver disease (NAFLD), which is associated with insulin resistance (IR). Fatty acid composition is critical for IR and subsequent NAFLD development. Extra-virgin olive oil (EVOO) is the main source of monounsaturated fatty acids (MUFA) in Mediterranean diets. This study examined whether EVOO-containing high fat diets may prevent diet-induced NAFLD using Ldlr-/-. Leiden mice. In female Ldlr-/-.Leiden mice, the effects of the following high fat diets (HFDs) were examined: a lard-based HFD (HFD-L); an EVOO-based HFD (HFD-EVOO); a phenolic compounds-rich EVOO HFD (HFD-OL). We studied changes in body weight (BW), lipid profile, transaminases, glucose homeostasis, liver pathology and transcriptome. Both EVOO diets reduced body weight (BW) and improved insulin sensitivity. The EVOOs did not improve transaminase values and increased LDL-cholesterol and liver collagen content. EVOOs and HFD-L groups had comparable liver steatosis. The profibrotic effects were substantiated by an up-regulation of gene transcripts related to glutathione metabolism, chemokine signaling and NF-kappa-B activation and down-regulation of genes relevant for fatty acid metabolism. Collectivelly, EVOO intake improved weight gain and insulin sensitivity but not liver inflammation and fibrosis, which was supported by changes in hepatic genes expression.

Point-of-care detection of neutrophils in live skin microsamples using chemiluminescence.

Many skin diseases are defined by the presence of neutrophils, which are among the first cells to respond to infection and inflammation. Currently, neutrophil identification in the skin is costly and slow. The objectives of the present work are to investigate the feasibility of detecting the presence of neutrophils in live skin microsamples using chemiluminescence and develop a device and procedures that will enable preclinical and clinical investigations. Our approach consists of collecting skin microsamples and exposing them to reagents that activate neutrophils and amplify the light emission produced by chemiluminescence. Experiments using live pig skin with and without inflammation show that it is feasible to detect the presence of neutrophils in the skin. The proposed method is minimally invasive, simple, fast, and does not require user specialization. The developed system is compact in size with a small footprint, which makes it portable and suitable for point-of-care diagnostics.

Experimental Estimation of a Second Order, Double Inverted Pendulum Parameters for the study of Human Balancing.

Balance control deteriorates naturally with age and is reliant upon the control of the ankle and hip joints. To this end, the estimation of ankle and hip parameters in quiet standing can be a useful tool when analyzing compensatory actions aimed at maintaining postural stability. This work presents an experimental study of a theoretical approach built upon previous results where the physiological parameters a second-order time-varying Kelvin-Voigt model are estimated for the actuation of the ankle and hip. These estimates are obtained using a double inverted pendulum based model subject to a step-like perturbation. Making use of RGB camera data to obtain the estimates of the system's visco-elastic parameters, the approach employed is capable of estimating the time-varying values for the body's control parameters. This work presents the first results of the method demonstrating the viability of a low-cost technique for regular testing of subjects with a high fall risk.

Rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2 cause potent neuroprotection after experimental stroke through noncompletely overlapping mechanisms.

Stroke triggers an inflammatory cascade which contributes to a delayed cerebral damage, thus implying that antiinflammatory strategies might be useful in the treatment of acute ischaemic stroke. Since two unrelated peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists, the thiazolidinedione rosiglitazone (RSG) and the cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2), have been shown to possess antiinflammatory properties, we have tested their neuroprotective effects in experimental stroke. Rosiglitazone or 15d-PGJ2 were administered to rats 10 mins or 2 h after permanent middle cerebral artery occlusion (MCAO). Stroke outcome was evaluated by determination of infarct volume and assessment of neurological scores. Brains were collected for protein expression, gene array analyses and gene shift assays. Our results show that both compounds decrease MCAO-induced infarct size and improve neurological scores. At late times, the two compounds converge in the inhibition of MCAO-induced brain expression of inducible NO synthase and the matrix metalloproteinase 9. Interestingly, at early times, complementary DNA microarrays and gene shift assays show that different mechanisms are recruited. Analysis of early nuclear p65 and late cytosolic IkappaBalpha protein levels shows that both compounds inhibit nuclear factor-kappaB signalling, although at different levels. All these results suggest both PPARgamma-dependent and independent pathways, and might be useful to design both therapeutic strategies and prognostic markers for stroke.

In vitro ischemic tolerance involves upregulation of glutamate transport partly mediated by the TACE/ADAM17-tumor necrosis factor-alpha pathway.

A short ischemic event [ischemic preconditioning (IPC)] can result in a subsequent resistance to severe ischemic injury (ischemic tolerance). Although tumor necrosis factor-alpha (TNF-alpha) contributes to the brain damage found after cerebral ischemia, its expression and neuroprotective role in models of IPC have also been described. Regarding the role of TNF-alpha convertase (TACE/ADAM17), we have recently shown its upregulation in rat brain after IPC induced by transient middle cerebral artery occlusion and that subsequent TNF-alpha release accounts for at least part of the neuroprotection found in this model. We have now used an in vitro model of IPC using rat cortical cultures exposed to sublethal oxygen-glucose deprivation (OGD) to investigate TACE expression and activity after IPC and the subsequent mechanisms of ischemic tolerance. OGD-induced cell death was significantly reduced in cells exposed to IPC by sublethal OGD 24 hr before, an effect that was inhibited by the TACE inhibitor BB3103 (1 microm) and anti-TNF-alpha antibody (2 microg/ml) and that was mimicked by TNF-alpha (10 pg/ml) preincubation. Western blot analysis showed that TACE expression is increased after IPC. IPC caused TNF-alpha release, an effect that was blocked by the selective TACE inhibitor BB-3103. In addition, IPC diminished the increase in extracellular glutamate caused by OGD and increased cellular glutamate uptake and expression of EAAT2 and EAAT3 glutamate transporters; however, only EAAT3 upregulation was mediated by increased TNF-alpha. These data demonstrate that neuroprotection induced by IPC involves upregulation of glutamate uptake partly mediated by TACE overexpression.

The nonthiazolidinedione PPARgamma agonist L-796,449 is neuroprotective in experimental stroke.

Some agonists of the peroxisome proliferator-activated receptor gamma (PPARgamma) belonging to the thiazolidinedione (TZD) family, as well as the cyclopentenone prostaglandin 15-dPGJ2, have been shown to cause neuroprotection in animal models of stroke. We have tested whether the TZD-unrelated PPARgamma agonist L-796,449 is neuroprotective after permanent middle cerebral artery occlusion (MCAO) in the rat brain. Our results show that L-796,449 decreases MCAO-induced infarct size and improves neurologic scores. This protection is concomitant to inhibition of MCAO-induced brain expression of inducible NO synthase (iNOS) and the matrix metalloproteinase MMP-9 and to upregulation of the cytoprotective stress protein heme oxygenase-1 (HO-1). Analysis of the NF-kappaB p65 monomer and the NF-kappaB inhibitor IkappaBalpha protein levels as well as gel mobility shift assays indicate that L-796,449 inhibits NF-kappaB signaling, and that it may be recruiting both PPARgamma-dependent and independent pathways. In summary, our results provide new insights for stroke treatment.

TNFR1 upregulation mediates tolerance after brain ischemic preconditioning.

A short ischemic event (ischemic preconditioning (IPC)) can result in subsequent resistance to severe ischemic injury (ischemic tolerance (IT)). The expression and neuroprotective role of tumor necrosis factor (TNF-alpha) have been described in models of IPC and we have showed the participation of its processing enzyme, the TNF-alpha convertase enzyme (TACE) in this process. We have now decided to explore the expression and localization of TNF receptors (TNFR) as well as other signalling mechanisms involved in IT. A period of 10 mins of temporary middle cerebral artery occlusion (tMCAO) was used for focal IPC. To evaluate the ability of IPC to produce IT, permanent MCAO was performed 48 hours after IPC. Ischemic preconditioning produced a reduction in infarct volume, as we showed previously. Ischemic preconditioning caused upregulation of neuronal TNFR1 that was reduced by the selective TACE inhibitor BB1101. Intracerebral administration of TNFR1 antisense oligodeoxynucleotide, which caused a reduction in TNFR1 expression, inhibited the IPC-induced protective effect, showing that TNFR1 upregulation is implicated in IT. Moreover, treatment with BB1101, TNFR1 antisense and lactacystin-a specific proteasome inhibitor-blocked IPC-induced NF-kappaB. Immunohistochemical studies showed the expression of TACE and TNFR1 in neurons. In summary, these data show that IPC produces neuronal upregulation of TACE and TNFR1, and that the pathway TACE/TNF-alpha/TNFR1/NF-kappaB is involved in IT.

Inhibition of glutamate release by delaying ATP fall accounts for neuroprotective effects of antioxidants in experimental stroke.

Excitotoxic neuronal injury related to excessive glutamate release is believed to play a key role in the pathogenesis of focal cerebral ischemia. Reversal of neuronal glutamate transporters caused by ATP fall and subsequent imbalance of membrane ionic gradients accounts for most glutamate release after cerebral ischemia. ATP synthesis from oxidative phosphorylation derives from the coupled functioning of the mitochondrial respiratory chain (MRC) and the ATP synthase; interestingly, the MRC is one of the main sites of cellular reactive oxygen species (ROS) generation even in physiological circumstances. Hence, we have studied the effect of the antioxidants glutathione, superoxide dismutase, and alpha-tocopherol on infarct outcome, brain ATP, and glutamate levels after permanent middle cerebral artery occlusion (MCAO) in Fischer rats; we have also characterized the actions of antioxidants on MRC complexes. Our results show that intraperitoneal administration of antioxidants 2 h before MCAO enhances ATP synthesis and causes a neuroprotective effect concomitant to inhibition of ischemia-induced increase in brain glutamate. Antioxidants also increased mitochondrial ATP and MRC complex I-III activity and respiration, suggesting that these actions are due to removal of the inhibition caused by endogenous ROS on MRC. These findings may possess important therapeutic repercussions in the management of ischemic stroke.

Inhibition of glutamate release via recovery of ATP levels accounts for a neuroprotective effect of aspirin in rat cortical neurons exposed to oxygen-glucose deprivation.

BACKGROUND AND PURPOSE: Aspirin is preventive against stroke not only because of its antithrombotic properties but also by other direct effects. The aim of this study was to elucidate its direct neuroprotective effects. METHODS: Viability parameters, glutamate release and uptake, and ATP levels were measured in cultured cortical neurons exposed to oxygen-glucose deprivation (OGD). In addition, ATP levels and oxygen consumption were studied in isolated brain mitochondria or submitochondrial particles. RESULTS: Aspirin inhibited OGD-induced neuronal damage at concentrations lower (0.3 mmol/L) than those reported to act via inhibition of the transcription factor nuclear factor-kappaB (which are >1 mmol/L), an effect that correlated with the inhibition caused by aspirin on glutamate release. This effect was shared by sodium salicylate but not by indomethacin, thus excluding the involvement of cyclooxygenase. A pharmacological dissection of the components involved indicated that aspirin selectively inhibits the increase in extracellular glutamate concentration that results from reversal of the glutamate transporter, a component of release that is due to ATP depletion. Moreover, aspirin-afforded neuroprotection occurred in parallel with a lesser decrease in ATP levels after OGD. Aspirin elevated ATP levels not only in intact cortical neurons but also in isolated brain mitochondria, an effect concomitant with an increase in NADH-dependent respiration by brain submitochondrial particles. CONCLUSIONS: Taken together, our present findings show a novel mechanism for the neuroprotective effects of aspirin, which takes place at concentrations in the antithrombotic-analgesic range, useful in the management of patients with high risk of ischemic events.