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  • Kilgore Welch posted an update 1 day, 7 hours ago

    Neurotransmitter transporters limit spillover between synapses and maintain the extracellular neurotransmitter concentration at low yet physiologically meaningful levels. They also exert a key role in providing precursors for neurotransmitter biosynthesis. In many cases, neurons and astrocytes contain a large intracellular pool of transporters that can be redistributed and stabilized in the plasma membrane following activation of different signaling pathways. This means that the uptake capacity of the brain neuropil for different neurotransmitters can be dynamically regulated over the course of minutes, as an indirect consequence of changes in neuronal activity, blood flow, cell-to-cell interactions, etc. Here we discuss recent advances in the mechanisms that control the cell membrane trafficking and biophysical properties of transporters for the excitatory, inhibitory and modulatory neurotransmitters glutamate, GABA, and dopamine.[This corrects the article DOI 10.3389/fnins.2016.00142.].Acute respiratory distress syndrome (ARDS) is the most severe form of acute lung injury. It is induced by sepsis, aspiration, and pneumonia, including that caused by SARS coronavirus and human influenza viruses. The main pathophysiological mechanism of ARDS is a systemic inflammatory response. Vagus nerve stimulation (VNS) can limit cytokine production in the spleen and thereby dampen any systemic inflammation and inflammation-induced tissue damage in the lungs and other organs. However, the effects of increased parasympathetic outflow to the lungs when non-selective VNS is applied may result in bronchoconstriction, increased mucus secretion and enhance local pulmonary inflammatory activity; this may outweigh the beneficial systemic anti-inflammatory action of VNS. Organ/function-specific therapy can be achieved by imaging of localized fascicle activity within the vagus nerve and selective stimulation of identified organ-specific fascicles. This may be able to provide selective neuromodulation of different pathways within the vagus nerve and offer a novel means to improve outcome in ARDS. This has motivated this review in which we discuss the mechanisms of anti-inflammatory effects of VNS, progress in selective VNS techniques, and a possible application for ARDS.

    The locus coeruleus noradrenergic (LC-NA) system is studied for its role in various neurological and psychiatric disorders such as epilepsy and Major Depression Dissorder. Chemogenetics is a powerful technique for specific manipulation of the LC to investigate its functioning. Local injection of AAV2/7 viral vectors has limitations with regards to efficiency and specificity of the transduction, potentially due to low tropism of AAV2/7 for LC neurons. In this study we used a canine adenovirus type 2 (CAV2) vector with different volumes and viral particle numbers to achieve high and selective expression of hM3Dq, an excitatory Designer Receptor Exclusively Activated by Designer Drugs (DREADD), for chemogenetic modulation of LC neurons.

    Adult male Sprague-Dawley rats were injected in the LC with different absolute numbers of CAV2-PRSx8-hM3Dq-mCherry physical particles (0.1E9, 1E9, 5E9,10E9, or 20E9 pp) using different volumes (LowV = 3 nl × 300 nl, MediumV = 3 × 600 nl, HighV = 3 × 1200 nl). Two weeks post-istudy the role of the LC-NA system in health and disease.

    This study identified optimal conditions (Low and Medium Volume with 0.1E9 particles of CAV2-PRSx8-hM3Dq-mCherry) for safe and specific transduction of LC neurons with excitatory DREADDs to study the role of the LC-NA system in health and disease.

    The severity of neurocognitive impairment increases with prematurity. However, its mechanisms remain poorly understood. Our aim was firstly to identify multiparametric magnetic resonance imaging (MRI) markers that differ according to the degree of prematurity, and secondly to evaluate the impact of clinical complications on these markers.

    We prospectively enrolled preterm infants who were divided into two groups according to their degree of prematurity extremely preterm (<28 weeks’ gestational age) and very preterm (28-32 weeks’ gestational age). They underwent a multiparametric brain MRI scan at term-equivalent age including morphological, diffusion tensor and arterial spin labeling (ASL) perfusion sequences. We quantified overall and regional volumes, diffusion parameters, and cerebral blood flow (CBF). We then compared the parameters for the two groups. We also assessed the effects of clinical data and potential MRI morphological abnormalities on those parameters.

    Thirty-four preterm infants were included. Extremely preterm infants (

    = 13) had significantly higher frontal relative volumes (

    = 0.04), frontal GM relative volumes (

    = 0.03), and regional CBF than very preterm infants, but they had lower brainstem and insular relative volumes (respectively

    = 0.008 and 0.04). Preterm infants with WM lesions on MRI had significantly lower overall GM CBF (13.3 ± 2 ml/100 g/min versus 17.7 ± 2.5, < ml/100 g/min

    = 0.03).

    Magnetic resonance imaging brain scans performed at term-equivalent age in preterm infants provide quantitative imaging parameters that differ with respect to the degree of prematurity, related to brain maturation.

    Magnetic resonance imaging brain scans performed at term-equivalent age in preterm infants provide quantitative imaging parameters that differ with respect to the degree of prematurity, related to brain maturation.

    Motor-vehicle crashes are frequent in untreated OSA patients but there is still uncertainty on prevalence as well as physiological or clinical determinants of sleepiness at the wheel (SW) in OSA patients. We assessed determinants of SW or sleepiness related near-miss car accident (NMA) in a group of non-professional drivers with OSA.

    A 237 consecutive, treatment-naïve PSG-diagnosed OSA patients (161 males, 53.1 ± 12.6 years) were enrolled. Self-reported SW was assessed by positive answer to the question, “Have you had episodes of falling asleep while driving or episodes of drowsiness at wheel that could interfere with your driving skill in the last year?” Occurrence of NMA in the last 3 years was also individually recorded. Habitual self-reported average sleep time was collected.

    SW was found in 41.3% of patients but one-quarter of patients with SW did not report excessive daytime sleepiness. RIN1 Predictors of SW were the following subjective factors Epworth sleepiness scale score (ESS-OR 1.26; IC 1.1-1.4;

    < 0.

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