Amperometric bio-sensing of lactate and oxygen concurrently with local field potentials during status epilepticus.

Epilepsy is a prevalent neurological disorder with a complex pathogenesis and unpredictable nature, presenting limited treatment options in >30 % of affected individuals. Neurometabolic abnormalities have been observed in epilepsy patients, suggesting a disruption in the coupling between neural activity and energy metabolism in the brain. In this study, we employed amperometric biosensors based on a modified carbon fiber microelectrode platform to directly and continuously measure lactate and oxygen dynamics in the brain extracellular space.

Astrocytic aerobic glycolysis provides lactate to support neuronal oxidative metabolism in the hippocampus.

Under physiological conditions, the energetic demand of the brain is met by glucose oxidation. However, ample evidence suggests that lactate produced by astrocytes through aerobic glycolysis may also be an oxidative fuel, highlighting the metabolic compartmentalization between neural cells. Herein, we investigate the roles of glucose and lactate in oxidative metabolism in hippocampal slices, a model that preserves neuron-glia interactions.

A Platinized Carbon Fiber Microelectrode-Based Oxidase Biosensor for Amperometric Monitoring of Lactate in Brain Slices.

Background: Direct and real-time monitoring of lactate in the extracellular space can help elucidate the metabolic and modulatory role of lactate in the brain. Compared to in vivo studies, brain slices allow the investigation of the neural contribution separately from the effects of cerebrovascular response and permit easy control of recording conditions.

Methods: We have used a platinized carbon fiber microelectrode platform to design an oxidase-based microbiosensor for monitoring lactate in brain slices with high spatial and temporal resolution operating at 32 °C.

Design and Evaluation of a Lactate Microbiosensor: Toward Multianalyte Monitoring of Neurometabolic Markers In Vivo in the Brain.

Direct in vivo measurements of neurometabolic markers in the brain with high spatio-temporal resolution, sensitivity, and selectivity is highly important to understand neurometabolism. Electrochemical biosensors based on microelectrodes are very attractive analytical tools for continuous monitoring of neurometabolic markers, such as lactate and glucose in the brain extracellular space at resting and following neuronal activation. Here, we assess the merits of a platinized carbon fiber microelectrode (CFM/Pt) as a sensing platform for developing enzyme oxidase-based microbiosensors to measure extracellular lactate in the brain.

Highly sensitive and selective nanostructured microbiosensors for glucose and lactate simultaneous measurements in blood serum and in vivo in brain tissue.

Highly sensitive and selective nanostructured lactate and glucose microbiosensors for their in vivo simultaneous determination in rat brain were developed based on carbon fiber microelectrodes (CFM) modified with nanoporous gold (NPG) using the Dynamic Hydrogen Bubble Template (DHBT) method. Electrodeposition of platinum nanoparticles (PtNP) onto the NPG film enhances the sensitivity and the electrocatalytic properties towards HO detection. The nanostructured microelectrode platform was modified by glucose oxidase (GOx) and lactate oxidase (LOx) enzyme immobilization.

Microelectrode Sensor for Real-Time Measurements of Nitrite in the Living Brain, in the Presence of Ascorbate.

The impaired blood flow to the brain causes a decrease in the supply of oxygen that can result in cerebral ischemia; if the blood flow is not restored quickly, neuronal injury or death will occur. Under hypoxic conditions, the production of nitric oxide (NO), via the classical L-arginine-NO synthase pathway, is reduced, which can compromise NO-dependent vasodilation. However, the alternative nitrite (NO) reduction to NO, under neuronal hypoxia and ischemia conditions, has been viewed as an in vivo storage pool of NO, complementing its enzymatic synthesis.

A High Fat/Cholesterol Diet Recapitulates Some Alzheimer's Disease-Like Features in Mice: Focus on Hippocampal Mitochondrial Dysfunction.

Background: Ample evidence from clinical and pre-clinical studies suggests mid-life hypercholesterolemia as a risk factor for developing Alzheimer's disease (AD) at a later age. Hypercholesterolemia induced by dietary habits can lead to vascular perturbations that increase the risk of developing sporadic AD.

Objective: To investigate the effects of a high fat/cholesterol diet (HFCD) as a risk factor for AD by using a rodent model of AD and its correspondent control (healthy animals).

An optimized spectrophotometric assay reveals increased activity of enzymes involved in 2-arachidonoyl glycerol turnover in the cerebral cortex of a rat model of Alzheimer's disease.

The endocannabinoid system is implicated in a plethora of neuropsychiatric disorders. However, it is technically challenging to assess the turnover of 2-arachidonoyl glycerol (2-AG), the principal endocannabinoid molecule in the brain. Two recent studies showed that diacylglycerol lipase α (DAGLα), an enzyme chiefly responsible for the cerebral production of 2-AG, also accepts the surrogate chromogenic substrate 4-nitrophenyl butyrate (4-NPB).

Electrochemical Evaluation of a Multi-Site Clinical Depth Recording Electrode for Monitoring Cerebral Tissue Oxygen.

The intracranial measurement of local cerebral tissue oxygen levels-PbtO-has become a useful tool for the critical care unit to investigate severe trauma and ischemia injury in patients. Our preliminary work in animal models supports the hypothesis that multi-site depth electrode recording of PbtO may give surgeons and critical care providers needed information about brain viability and the capacity for better recovery. Here, we present a surface morphology characterization and an electrochemical evaluation of the analytical properties toward oxygen detection of an FDA-approved, commercially available, clinical grade depth recording electrode comprising 12 Pt recording contacts.

The Peculiar Facets of Nitric Oxide as a Cellular Messenger: From Disease-Associated Signaling to the Regulation of Brain Bioenergetics and Neurovascular Coupling.

In this review, we address the regulatory and toxic role of NO along several pathways, from the gut to the brain. Initially, we address the role on NO in the regulation of mitochondrial respiration with emphasis on the possible contribution to Parkinson's disease via mechanisms that involve its interaction with a major dopamine metabolite, DOPAC. In parallel with initial discoveries of the inhibition of mitochondrial respiration by NO, it became clear the potential for toxic NO-mediated mechanisms involving the production of more reactive species and the post-translational modification of mitochondrial proteins.

Changes health-related quality of life in HIV-infected patients following initiation of antiretroviral therapy: a longitudinal study.

Background: Several tools have been developed to evaluate HIV health-related quality of life (HRQoL) during and after antiretroviral therapy (ART). Few longitudinal studies evaluated the effect of ART on the quality of life of HIV patients.

Objective: To evaluate changes in HRQoL in HIV-infected individuals one year after initiating ART.

Platinized carbon fiber-based glucose microbiosensor designed for metabolic studies in brain slices.

In order to understand how energy metabolism adapts to changes in neuronal activity it is imperative to perform direct measurements of the flux of glucose (and other metabolites) in brain tissue. Metabolic studies using brain slice preparations are attractive due to the controllability of recording conditions, absence of anesthetic interference and refined animal experimental protocols. In this work, taking advantage of the small size and versatility of carbon fiber microelectrodes (CFMs), we aimed to develop an amperometric glucose microbiosensor suitable for glucose measurement in brain slices.

Muscle Strength and Aerobic Capacity in HIV-Infected Patients: A Systematic Review and Meta-Analysis.

Background: Physical impairment is highly prevalent in HIV-infected patients. We conducted a systematic review of published studies that included studies comparing muscle function in HIV-infected patients to matched healthy controls, and studies comparing aerobic capacity in HIV-infected patients with that observed in matched healthy controls.

Design: Systematic review and meta-analysis.

Association Between Health-Related Quality of Life and Physical Functioning in Antiretroviral-Naive HIV-Infected Patients.

Background: Poor functional status can significantly affect Health-Related Quality of Life (HRQoL) of HIV patients. However, there is scarce information on the functional profile of such patients before starting antiretroviral therapy (ART).

Objective: To estimate the association between health-related quality of life and physical functioning in Antiretroviral-Naive HIV-infected patients.

Age-Dependent Impairment of Neurovascular and Neurometabolic Coupling in the Hippocampus.

Neurovascular and neurometabolic coupling are critical and complex processes underlying brain function. Perturbations in the regulation of these processes are, likely, early dysfunctional alterations in pathological brain aging and age-related neurodegeneration. Evidences support the role of nitric oxide (•NO) as a key messenger both in neurovascular coupling, by signaling from neurons to blood vessels, and in neurometabolic coupling, by modulating O utilization by mitochondria.

Modulation of Cellular Respiration by Endogenously Produced Nitric Oxide in Rat Hippocampal Slices.

Nitric oxide (NO) is an ubiquitous signaling molecule that participates in molecular processes associated with several neural phenomena ranging from memory formation to excitotoxicity. In the hippocampus, neuronal NO production is coupled to the activation of NMDA type glutamate receptors. Cytochrome c oxidase has emerged as a novel target for NO, which competes with O for binding to this mitochondrial complex.

Analysis of respiratory capacity in brain tissue preparations: high-resolution respirometry for intact hippocampal slices.

The evaluation of mitochondrial function provides the basis for the study of brain bioenergetics. However, analysis of brain mitochondrial respiration has been hindered by the low yield associated with mitochondria isolation procedures. Furthermore, isolating mitochondria or cells results in loss of the inherent complexity of the central nervous system.

Simultaneous measurements of ascorbate and glutamate in vivo in the rat brain using carbon fiber nanocomposite sensors and microbiosensor arrays.

Nanocomposite sensors consisting of carbon fiber microelectrodes modified with Nafion® and carbon nanotubes, and ceramic-based microelectrode biosensor arrays were used to measure ascorbate and glutamate in the brain with high spatial, temporal and chemical resolution. Nanocomposite sensors displayed electrocatalytic properties towards ascorbate oxidation, translated into a negative shift from +0.20V to -0.

Combined in Vivo Amperometric Oximetry and Electrophysiology in a Single Sensor: A Tool for Epilepsy Research.

Seizures are paroxysmal events in which increased neuronal activity is accompanied by an increase in localized energetic demand. The ability to simultaneously record electrical and chemical events using a single sensor poses a promising approach to identify seizure onset zones in the brain. In the present work, we used ceramic-based platinum microelectrode arrays (MEAs) to perform high-frequency amperometric recording of local pO and local field potential (LFP)-related currents during seizures in the hippocampus of chronically implanted freely moving rats.

Neurometabolic and electrophysiological changes during cortical spreading depolarization: multimodal approach based on a lactate-glucose dual microbiosensor arrays.

Spreading depolarization (SD) is a slow propagating wave of strong depolarization of neural cells, implicated in several neuropathological conditions. The breakdown of brain homeostasis promotes significant hemodynamic and metabolic alterations, which impacts on neuronal function. In this work we aimed to develop an innovative multimodal approach, encompassing metabolic, electric and hemodynamic measurements, tailored but not limited to study SD.

Abdominal Near-Infrared Spectroscopy Detects Low Mesenteric Perfusion Early in Preterm Infants with Hemodynamic Significant Ductus Arteriosus.

Background: The therapeutic decision to close patent ductus arteriosus in preterm infants entails great uncertainty. Near-infrared spectroscopy is a noninvasive bedside technique used to monitor mixed regional oxygen saturation. We hypothesized that near-infrared spectroscopy could identify preterm infants at risk of mesenteric hypoperfusion associated with hemodynamically significant ductus arteriosus.

Neurovascular-neuroenergetic coupling axis in the brain: master regulation by nitric oxide and consequences in aging and neurodegeneration.

The strict energetic demands of the brain require that nutrient supply and usage be fine-tuned in accordance with the specific temporal and spatial patterns of ever-changing levels of neuronal activity. This is achieved by adjusting local cerebral blood flow (CBF) as a function of activity level - neurovascular coupling - and by changing how energy substrates are metabolized and shuttled amongst astrocytes and neurons - neuroenergetic coupling. Both activity-dependent increase of CBF and O and glucose utilization by active neural cells are inextricably linked, establishing a functional metabolic axis in the brain, the neurovascular-neuroenergetic coupling axis.

Ceramic-Based Multisite Platinum Microelectrode Arrays: Morphological Characteristics and Electrochemical Performance for Extracellular Oxygen Measurements in Brain Tissue.

Ceramic-based multisite Pt microelectrode arrays (MEAs) were characterized for their basic electrochemical characteristics and used for in vivo measurements of oxygen with high resolution in the brain extracellular space. The microelectrode array sites showed a very smooth surface mainly composed of thin-film polycrystalline Pt, with some apparent nanoscale roughness that was not translated into an increased electrochemical active surface area. The electrochemical cyclic voltammetric behavior was characteristic of bulk Pt in both acidic and neutral media.