Neuroscience
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Stroke is a leading cause of death and serious, long-term disability worldwide. We report that rats receiving liraglutide show markedly attenuated infarct volumes and neurological deficit following ischemic insult. We have also investigated the effect of liraglutide on apoptosis and oxidative stress pathways after ischemic injury in diabetic and non-diabetic rats. ⋯ The number of TUNEL-positive cells in vehicle group was 73.5±3.3 and 85.5±5.2/750μm(2) in non-diabetic and diabetic vehicle-treated MCAO rats, respectively. Following liraglutide treatment the number of TUNEL-positive cells was remarkably attenuated to 25.5±2.8 and 41.5±4.1/750μm(2) (p<0.001) in non-diabetic and diabetic rats, respectively. The results demonstrate that glucagon-like peptide 1 (GLP-1) agonist, liraglutide, is a neuroprotective agent and attenuates the neuronal damage following cerebral ischemia in rats by preventing apoptosis and decreasing oxidative stress.
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Protease activated receptors (PARs) populate neurons and astrocytes in the brain. The serine protease thrombin, which activates PAR-1 during the first hours after stroke, appears to be associated with the cytotoxicity. Thrombin antagonists and PAR-1 inhibitors have been correlated with reduced cell death and behavioral protection after stroke, but no data yet support a mechanistic link between PAR-1 action and benefit. ⋯ We demonstrated an essential role for PAR-1 during ischemia. Silencing or removing PAR-1 significantly protected neurons and astrocytes. Further development of agents that act at PAR-1 or its downstream pathways could yield powerful stroke therapy.
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Despite the debilitating consequences and the widespread prevalence of brain trauma insults including spinal cord injury (SCI) and traumatic brain injury (TBI), there are currently few effective therapies for most of brain trauma sequelae. As a consequence, there has been a major quest for identifying better diagnostic tools, predictive models, and directed neurotherapeutic strategies in assessing brain trauma. Among the hallmark features of brain injury pathology is the central nervous systems' (CNS) abnormal activation of the immune response post-injury. ⋯ It is being suggested that there may be an analogy of CNS autoantibodies secretion with the pathophysiology of autoimmune diseases, in which case, understanding and defining the role of autoantibodies in brain injury paradigm (SCI and TBI) may provide a realistic prospect for the development of effective neurotherapy. In this work, we will discuss the accumulating evidence about the appearance of autoantibodies following brain injury insults. Furthermore, we will provide perspectives on their potential roles as pathological components and as candidate markers for detecting and assessing CNS injury.
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Physical activity has been demonstrated to diminish age-related brain volume shrinkage in several brain regions accompanied by a reduction of age-related decline in cognitive functions. Most studies investigated the impact of cardiovascular fitness or training. Other types of fitness or training are less well investigated. ⋯ Additionally, a moderating effect of the volume of the basal ganglia (as a whole, but also separately for putamen and globus pallidus) on the relationship between motor fitness and executive function was revealed. Coordination training increased caudate and globus pallidus volume. We provide evidence that coordinative exercise seems to be a favorable leisure activity for older adults that has the potential to improve volume of the basal ganglia.
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Neuropathy target esterase (NTE) is a protein involved in the development of a polyneuropathy caused by exposure to certain organophosphorus compounds. In vivo and in vitro studies have also associated NTE with embryonic development since NTE null mice embryos are non-viable, and silencing the NTE-codifying gene (Pnpla6) in mouse embryonic stem cells strongly alters the differentiation of vascular and nervous systems. In this paper, human embryonal carcinoma stem cells human-derived NTera2/D1 (hNT2) are used as an in vitro neurodifferentiation model to determine whether PNPLA6 silencing is able to alter the differentiation process. ⋯ Microarray data analysis of the PNPLA6-silenced cells showed alterations in several developmental processes, mainly neurogenesis and epithelium tube morphogenesis. PNPLA6 silencing also led to a reduction in electrical activity and an altered neuronal phenotype. This work is the first proof supporting the hypothesis that NTE plays a role in human early neurodevelopment using a human cell differentiation model.