Plos One
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Opiates are powerful drugs to treat severe pain, and act via mu opioid receptors distributed throughout the nervous system. Their clinical use is hampered by centrally-mediated adverse effects, including nausea or respiratory depression. Here we used a genetic approach to investigate the potential of peripheral mu opioid receptors as targets for pain treatment. ⋯ We therefore genetically demonstrate for the first time that mu opioid receptors partly mediate opiate analgesia at the level of Nav1.8-positive sensory neurons. In our study, this mechanism operates under conditions of inflammatory pain, but not nociception. Previous pharmacology suggests that peripheral opiates may be clinically useful, and our data further demonstrate that Nav1.8 neuron-associated mu opioid receptors are feasible targets to alleviate some forms of persistent pain.
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Methylene blue (MB) has unique energy-enhancing and antioxidant properties and is FDA-approved drug to treat methemoglobinemia and cyanide poisoning. This study evaluated the efficacy of MB to treat ischemic stroke in rats using longitudinal MRI and behavioral measures. Rats were subjected to 60-minute middle-cerebral-artery occlusion. ⋯ The final infarct volumes two days after stroke increased in the vehicle group but decreased in the MB group, yielding a 30% difference in infarct volume (P = 0.03). Tracking tissue fate on a pixel-by-pixel basis showed that MB salvaged more initial core pixels compared to controls (22±3% versus 11±3%, P = 0.03), and more mismatch pixels compared to controls (83±3% versus 61±8%, P = 0.02). This study demonstrates MB treatment minimizes ischemic brain injury and improves functional outcomes.
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A key problem in neuroscience is understanding how the brain makes decisions under uncertainty. Important insights have been gained using tasks such as the random dots motion discrimination task in which the subject makes decisions based on noisy stimuli. A descriptive model known as the drift diffusion model has previously been used to explain psychometric and reaction time data from such tasks but to fully explain the data, one is forced to make ad-hoc assumptions such as a time-dependent collapsing decision boundary. ⋯ We show that the motion discrimination task reduces to the problems of (1) computing beliefs (posterior distributions) over the unknown direction and motion strength from noisy observations in a bayesian manner, and (2) selecting actions based on these beliefs to maximize the expected sum of future rewards. The resulting optimal policy (belief-to-action mapping) is shown to be equivalent to a collapsing decision threshold that governs the switch from evidence accumulation to a discrimination decision. We show that the model accounts for both accuracy and reaction time as a function of stimulus strength as well as different speed-accuracy conditions in the random dots task.
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Hemorrhagic shock and resuscitation induces pulmonary inflammation that leads to acute lung injury. Biliverdin, a metabolite of heme catabolism, has been shown to have potent cytoprotective, anti-inflammatory, and anti-oxidant effects. This study aimed to examine the effects of intravenous biliverdin administration on lung injury induced by hemorrhagic shock and resuscitation in rats. ⋯ Biliverdin administration prior to hemorrhagic shock and resuscitation decreased mitochondrial 8-hydroxy-2' deoxyguanosine levels to almost the same level as that in the control animals. We also confirmed that biliverdin administration after hemorrhagic shock and resuscitation had protective effects on lung injury. Our findings suggest that biliverdin has a protective role, at least in part, against hemorrhagic shock and resuscitation-induced lung injury through anti-inflammatory and anti-oxidant mechanisms.
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Intraoperative brain stimulation mapping reduces permanent postoperative deficits and extends tumor removal in resective surgery for glioma patients. Successful functional mapping is assumed to depend on the surgical team's expertise. In this study, glioma resection results are quantified and compared using a novel approach, so-called resection probability maps (RPM), exemplified by a surgical team comparison, here with long and short experience in mapping. ⋯ RPMs provide a quantitative volumetric method to compare resection results, which we present as standard for quality assessment of resective glioma surgery because brain location bias is avoided. Stimulation mapping is a robust surgical technique, because the neurological outcome and functional-based resection results using stimulation mapping are independent of surgical experience, supporting wider implementation.