Neuroscience
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Colivelin is a neuroprotective humanin family peptide with potent long-term capacity against Aβ deposition, neuronal apoptosis, and synaptic plasticity deficits in neurodegenerative disease. We seek to investigate whether this effect of Colivelin also govern ischemic brain injury, and potential mechanism underlying the Colivelin-mediated action on ischemic neurons. We adopted 60 min induction of transient focal cerebral ischemia and reperfusion in mice. ⋯ Moreover, Colivelin activated STAT3 signaling, which may partially contribute to its beneficial effect against neuronal death and axon growth. In conclusion, Colivelin induce anti-apoptotic genes up-regulation, and activate JAK/STAT3 signaling after ischemic stroke, which may contribute to its effects of rescuing ischemic neuronal death and axonal remodeling. This study may justify further works to examine Colivelin as a single or adjunct therapy in ischemic stroke.
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Multiple sclerosis (MS) is a demyelination disease that causes gradual damage to neurons. Despite the necessity of appropriate treatments at each disease stage to prevent the worsening of the damage, it is still difficult to cure MS. In this study, metabolomics and lipidomics studies were performed with time-course plasma samples (early, peak, chronic phase for MS) to elucidate the mechanism during MS progression after induction of experimental autoimmune encephalomyelitis (EAE), which is the animal model for multiple sclerosis (MS). ⋯ In particular, 26 metabolites showed significant differences at specific stages. The metabolite level of the plasma was significantly altered in response to the EAE pathogenesis, and these changes were related to inflammation status at each disease stage. This study can provide crucial information for reducing damage by differentiating treatment strategies according to disease progression.
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Nerve damage leads to the development of disabling neuropathic pain in susceptible individuals, where patients present with pain as well as co-morbid affective behavioural disturbances, such as anhedonia, decreased motivation and depression. In this study we aimed to characterise changes in neuroinflammation in the medial prefrontal cortex (mPFC) and hippocampus (HP) in a rat model of neuropathic pain (NP) and behavioural changes. 53 rats underwent sciatic nerve chronic constriction injury (CCI) and were characterised as either, No effect, Acute effect or Lasting effect on the basis of changes in exploration behaviour in a radial-arm maze. Microglial and astrocyte morphology, as well as IL-1β, IL-6, IL-10, MCP-1, p38 MAPK and BDNF expression was quantified throughout the mPFC and HP using protein multiplex assays and immunofluorescence. ⋯ This includes increased expression of IL-1β, IL-6 and MCP-1, increased phospho-p38 MAPK expression in neurons and microglia, and a shift to a reactive microglial morphology in the caudal PL and IL, ventral CA1 and DG. Therefore, neuroinflammation in the mPFC and ventral HP may influence individual differences in radial-arm maze behaviour following CCI. Our data provide further evidence that individual differences in neuroimmune activation in the interconnected ventral HP-mPFC circuitry may play a role in the divergent behavioural trajectories following nerve injury, with neuroinflammation being coincident with affective behavioural changes in susceptible individuals.
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There are many uncontrollable factors in the pathogenesis of cerebral venous sinus thrombosis (CVST). In order to further explore the pathophysiology and morphology of CVST, it is necessary to establish a highly compatible CVST animal model that can standardize the site and stage of venous thrombosis. The present study employed the insertion of a self-made thread embolism into the superior sagittal sinus (SSS) to establish a rat model of SSS occlusion that emulates CVST. ⋯ Removing SSS occlusion significantly improved cerebral circulation, reduced brain edema, and accelerated the receding of brain edema. This study established a new model of acute occlusion and recanalization of SSS in rats via a thread-embolism method, which standardized the ischemic site and stage of venous thrombosis. In addition, our study suggests that promoting collateral circulation may be a potential treatment for promoting brain protection.
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Turning elicits Freezing of Gait (FoG) episodes in people with Parkinson's disease (PD) and is thought to require higher cortical control compared to straight ahead gait. Functional near infrared spectroscopy (fNIRS) has been used to examine prefrontal cortex (PFC) activity while walking, but the relationship between PFC activity and turn performance remains unclear. The aim of this pilot study was to examine PFC activity during turning in PD and healthy controls, and to investigate the association between PFC activity and turning. ⋯ In addition, higher PFC is associated with worse FoG in PD + FoG (r = 0.57, p = .048) and with lower number of turns in PD - FoG (r = -0.70, p = .002). The increased PFC activity in PD and the association between higher PFC activity and poorer turning performance may be a sign of poor movement automaticity in PD. Although further investigations are required, these pilot findings may guide development of personalized treatments to improve motor automaticity in PD.