Neuroscience
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Spinal cord injury (SCI) is a devastating neurological event that results in incomplete or complete loss of voluntary motor and sensory function. Until recently, there has been no effective curative strategy for SCI. Our previous study showed that microRNA (miR)-126 promoted angiogenesis and attenuated inflammation after SCI; however, the effect of miR-126-based treatment is limited because of the low efficiency of miR delivery in vivo. ⋯ In vitro, we observed that exosomes derived from miR-126-modified MSCs promoted the angiogenesis and migration of human umbilical venous endothelial cells (HUVECs) by inhibiting the expression of Sprouty-related EVH1 domain-containing protein 1 (SPRED1) and phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2). In conclusion, our study demonstrated that exosomes derived from MSCs transfected with miR-126 may promote angiogenesis and neurogenesis, inhibit apoptosis and promote functional recovery after SCI. These findings suggest that exosomes derived from miR-126-modified MSCs may serve as a novel potential therapeutic strategy for treating SCI.
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Maternal consumption of ethanol during pregnancy is known to increase the offspring's risk for developing alcohol use disorders and associated behavioral disturbances. Studies in adolescent and adult animals suggest the involvement of neuroimmune and neurochemical systems in the brain that control these behaviors. ⋯ We also discovered that these effects are sexually dimorphic, consistently stronger in female embryos, and are blocked by maternal administration of a CCL2 antibody (1 and 5 µg/day, i.p., E10-E15) that neutralizes endogenous CCL2 and of a CCR2 antagonist INCB3344 (1 mg/day, i.p., E10-E15) that blocks CCL2's main receptor. These results, which in the embryo anatomically and functionally link the CCL2/CCR2 system to MCH neurons in the LH, suggest an important role for this neuroimmune system in mediating ethanol's sexually dimorphic, stimulatory effect on MCH neurons that may promote higher level of alcohol consumption described in females.
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The administration of glucocorticoids (GCs) for the treatment of traumatic brain injury (TBI) is controversial. Both protective and deleterious effects of GCs on the brain have been reported in previous studies, while the mechanisms are unclear. Most experimental studies have reported glucocorticoid receptor (GR)-mediated deleterious effects after TBI. ⋯ Fludrocortisone treatment significantly increased both the expression and activation of MRs, reduced the number of apoptotic neurons and cell loss in the ipsilateral hippocampus, and subsequently improved spatial memory. Its protective effects were counteracted by the MR antagonist spironolactone. The results suggest that adequate expression and activation of MRs is crucial for the survival of neurons after TBI and that fludrocortisone protects hippocampal neurons via promoting MR expression and activation.
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Near threshold stochastic vestibular stimulation (SVS) enhances postural control and improves other symptoms in neurodegenerative disorders like Parkinson's disease (PD). Improvement of postural control can tentatively be explained by increased responsivity of the vestibular system, but the mechanism behind other effects of near threshold SVS, like improved motor symptoms and cognitive responsiveness in PD, are not known. To better understand the effect of vestibular stimulation on brain activity in PD, c-Fos expression was used as a marker of change in functional activity following SVS in 6-hydroxydopamine (6-OHDA) hemi-lesioned and in sham-lesioned rats. ⋯ Furthermore, c-Fos expression increased more in the habenula nucleus (LHb) after SVS than it did after levodopa in 6-OHDA hemilesioned animals and after saline in the sham-lesioned animals. SVS and levodopa induced similar c-Fos expression in several regions, e.g. the caudate putamen (CPu), where saline had no effect. In conclusion there was overlap between SVS-activated areas and levodopa-activated areas, but activation was more pronounced following SVS in the MVePC of 6-OHDA lesioned and in the LHb in both lesioned and sham-lesioned rats.