Neuroscience
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Intracranial hypertension (IH) is a medical or surgical emergency that can be the common ending of various neurological disorders, such as traumatic brain injury, cerebral vascular diseases and brain tumors. However, the molecular mechanisms underlying IH-induced neuronal apoptosis have not been fully determined, and the treatments are symptomatic, insufficient and complicated by side-effects. In this study, a cellular model induced by compressed gas treatment in primary cultured rat cortical neurons was performed to mimic IH-induced neuronal injury in vitro. ⋯ Furthermore, the results using inhibitors of each signaling pathway demonstrated that ROS mediated the compression-induced ER stress and mitochondrial dysfunction in cortical neurons. In conclusion, our results demonstrated that compression induced apoptosis in primary cultured cortical neurons, which was associated with ROS mediated ER stress and mitochondrial dysfunction. Pharmacological compounds or agents targeting mitochondrial dysfunction and ER stress associated oxidative stress might be ideal candidates for the treatment of IH-related neurological diseases.
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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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Given their anti-inflammatory properties, cannabinoids have been shown to be neuroprotective agents and to reduce excitotoxicity, through the activation of the Cannabinoid receptor type 1 (CB1r). These properties have led to CB1r being proposed as pharmacological targets for the treatment of various neurodegenerative diseases. Amyloid-β 25-35 (Aβ25-35) induces the expression of inducible nitric oxide synthase (iNOS) and increases nitric oxide (NO●) levels. ⋯ Moreover, ACEA plus Aβ(25-35) prevented both the increase in iNOS protein and NO● levels and the reactive gliosis induced by Aβ(25-35). Importantly, neurodegeneration was significantly reduced by the administration of ACEA plus Aβ(25-35) in the CA1 subfield of the hippocampus. The data obtained in the present research suggest that the acute early activation of CB1r is crucial for neuroprotection.
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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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Reproductive experience in mammals produces significant neuroendocrine and behavioral changes that are necessary to ensure the survival of the mother and the young. Exposure to stress during postpartum may affect the proper development of maternal behaviors. The present study examined whether previous reproductive experience affects neurobehavioral responses in females exposed to mother-infant separation stress during the postpartum period (4.5 h/day for 3 weeks). ⋯ Multiparity increased cell proliferation and cell survival in female rats and these changes occurred independently of pup exposure. The expression of BDNF was higher in the CA1 area in MULT rats. Although multiparity protects the mother against some of the effects of maternal separation stress, promoting behaviors directed to the pups during the early postpartum, preventing anxiety-like behaviors and mitigating memory deterioration after weaning, the data showed that disrupting natural dam-pup interaction produced neurobiological consequences on the mother even with multiple reproductive experience.