Articles: human.
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Over recent years evidence from animal studies strongly suggests that a decrease in local inhibitory signaling is necessary for synaptic plasticity to occur. However, the role of GABAergic modulation in human motor plasticity is less well understood. Here, we summarize the techniques available to quantify GABA in humans, before reviewing the existing evidence for the role of inhibitory signaling in human motor plasticity. We discuss a number of important outstanding questions that remain before the role of GABAergic modulation in long-term plasticity in humans, such as that underpinning recovery after stroke, can be established.
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J Neurosurg Anesthesiol · Oct 2014
ReviewEngaging Stakeholders in Research Related to Anesthesia and Neurodevelopment in Children.
The Fourth PANDA symposium on Anesthesia and Neurodevelopment in Children invited 4 leaders in community engagement and federal government collaboration to share their experiences with overcoming challenges in promoting public health issues. There continues to be emerging evidence from laboratory findings in animal models demonstrating neurotoxic effects and neurodevelopmental changes from early exposure to anesthetic and sedative drugs, but studies in humans have been very limited and inconclusive. Although definitive recommendations for clinical care still cannot be made given the limitations in the clinical data, the need for open communication among clinicians, parents, and other stakeholders is clear. ⋯ To reach the goal of "improving quality, safety, efficiency, and effectiveness of health care in children," clinicians and researchers will need to adopt strategies to engage and partner with stakeholders as coinvestigators who actively participate in efforts to increase anesthetic safety in children. Collaborations with government regulatory administration can improve the efficacy and effectiveness of resource utilization to address public health needs. This session provided an opportunity for open dialog between clinicians, researchers, and community leaders to discuss strategies to engage stakeholders to partake in patient-centered outcomes research on anesthetic neurotoxicity.
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The importance of the modulation of pain by emotion is now widely recognised. In particular, stress and anxiety, depending on their nature, duration and intensity, can exert potent, but complex, modulatory influences typified by either a reduction or exacerbation of the pain state. ⋯ Preclinical studies of SIH are essential for our understanding of the mechanisms underpinning stress-related pain syndromes and for the identification of neural pathways and substrates, and the development of novel therapeutic agents for their clinical management. In this review, we describe clinical and pre-clinical models used to study SIH and discuss the neural substrates, neurotransmitters and neuromodulatory systems involved in this phenomenon.
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J Neurosurg Anesthesiol · Oct 2014
ReviewClinical Research Into Anesthetic Neurotoxicity: Does Anesthesia Cause Neurological Abnormalities in Humans?
General anesthetics mitigate distress and exaggerated hemodynamic responses to pain and stressful stimulation, allowing surgery and diagnostic procedures to be performed worldwide in millions of children every year. Emerging studies, mainly carried out in early postnatal laboratory animals, demonstrate widespread neuronal elimination, alteration in neuronal circuitry, and long-term neurological disabilities following exposure to all commonly used sedatives and anesthetics. These findings have raised concerns among parents, anesthesiologists, neuroscientists, and government regulators about the safety of anesthetic drugs in children, especially infants. ⋯ During the Fourth Pediatric Anesthesia NeuroDevelopmental Assessment (PANDA) symposium, a meeting attended by many stakeholders, the most recent findings in the field were presented and discussed. This review summarizes the current state of clinical research into the effects of anesthetic exposure in human brain development, addresses some of the difficulties in examining the phenomenon, and introduces the most recent clinical findings presented at the PANDA symposium. The unanimous consensus among participants was that additional preclinical and clinical research efforts are urgently required to address this important concern for child health.
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Acute lung injury (ALI) and ARDS fall within a spectrum of pulmonary disease that is characterized by hypoxemia, noncardiogenic pulmonary edema, and dysregulated and excessive inflammation. While mortality rates have improved with the advent of specialized ICUs and lung protective mechanical ventilation strategies, few other therapies have proven effective in the management of ARDS, which remains a significant clinical problem. Further development of biomarkers of disease severity, response to therapy, and prognosis is urgently needed. ⋯ This review will focus on the roles of matrix metalloproteinases and protein tyrosine kinases in the pathobiology of ALI in humans, and in animal models and in vitro studies. These molecules can act independently, as well as coordinately, in a feed-forward manner via activation of tyrosine kinase-regulated pathways that are pivotal in the development of ARDS. Specific signaling events involving proteolytic processing by matrix metalloproteinases that contribute to ALI, including cytokine and chemokine activation and release, neutrophil recruitment, transmigration and activation, and disruption of the intact alveolar-capillary barrier, will be explored in the context of these novel molecular pathways.