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05). Collectively, these findings suggest that the cumulative effects of repeated gravitational transitions may promote minor blood-brain barrier disruption, potentially related to the combined effects of haemodynamic (posterior cerebral hyperperfusion) and molecular (systemic oxidative-nitrosative) stress.Vascular endothelial cells were activated during acute ischemic brain injury, which could induce neural progenitor cell proliferation and migration. However, the mechanism was still unknown. In the current study, we explored whether vascular endothelial cells promoted neural progenitor cell proliferation and whether migration occurs via exosome communication. The acute middle cerebral artery occlusion (MCAO) model was prepared, and exosomes were isolated from bEnd.3 cells by ultracentrifugation. In the exosome injection (Exos) group and PBS injection (control) group, exosomes or PBS were injected intraventricularly into rats’ brains 2 h after MCAO surgery, respectively. Sham group rats received the same surgical but did not cause middle cerebral artery occlusion. The infarct volume was reduced on day 21 after ischemic brain injury by MRI, and neurobehavioral outcomes were improved on day 7, 14, and 21 by exosome injection compared with the control (p less then 0.05). On the 21st day after MCAO, the animals were euthanized, and the number of BrdU/nestin-positive cells was measured by immunofluorescence. BrdU/nestin-positive cells in Exos group rats were significantly increased (p less then 0.05) in the peri infarct area, the ipsilateral DG zone of the hippocampus, and the ventral sub-regions of SVZ when compared with the rats in the control group. Further, in vitro study demonstrated that neural progenitor cell proliferation and migration were activated after exosomes treatment, and cell apoptosis was attenuated compared to the control (p less then 0.05). Our study suggested that exosomes should be essential for the reconstruction of neuronal vascular units and brain protection in an acute ischemic injured brain.α-Synuclein (α-Syn) is a key pathogenic protein in α-synucleinopathies including Parkinson disease (PD) and Dementia with Lewy Bodies. The aggregation of α-Syn is believed to be deleterious and a critical step leading to neuronal dysfunction and death. One of the factors that may contribute to the initial steps of this aggregation is crosslinking through transglutaminase 2 (TG2). We previously demonstrated that overexpression of TG2 exacerbates α-Syn toxicity in mice and yeast by increasing the higher-order species of α-Syn. Herein, we investigated whether deletion of the TG2 encoding gene could mitigate the toxicity of α-Syn in vivo. Compared with α-Syn transgenic (SynTg) mice, TG2 null /α-Syn transgenic mice (TG2KO/SynTg) exhibited a reduced amount of phosphorylated α-Syn aggregates and fewer proteinase K-resistant α-Syn aggregates in sections of brain tissue. learn more Neuritic processes that are depleted in SynTg mice compared to wild-type mice were preserved in double TG2KO/SynTg mice. Additionally, the neuroinflammatory reaction to α-Syn was attenuated in TG2KO/SynTg animals. These neuropathological markers of diminished α-Syn toxicity in the absence of TG2 were associated with better motor performance on the rotarod and balance beam. These results suggest that deleting TG2 reduces the toxicity of α-Syn in vivo and improves the behavioral performance of SynTg mice. Accordingly, these findings collectively support pharmacological inhibition of TG2 as a potential disease modifying therapeutic strategy for α-synucleinopathies.The cerebellum forms regular neural network structures consisting of a few major types of neurons, such as Purkinje cells, granule cells, and molecular layer interneurons, and receives two major inputs from climbing fibers and mossy fibers. Its regular structures consist of three well-defined layers, with each type of neuron designated to a specific location and forming specific synaptic connections. During the first few weeks of postnatal development in rodents, the cerebellum goes through dynamic changes via proliferation, migration, differentiation, synaptogenesis, and maturation, to create such a network structure. The development of this organized network structure presumably relies on the communication between developing elements in the network, including not only individual neurons, but also their dendrites, axons, and synapses. Therefore, it is reasonable that extracellular signaling via synaptic transmission, secreted molecules, and cell adhesion molecules, plays important roles in cerebellar network development. Although it is not yet clear as to how overall cerebellar development is orchestrated, there is indeed accumulating lines of evidence that extracellular signaling acts toward the development of individual elements in the cerebellar networks. In this article, we introduce what we have learned from many studies regarding the extracellular signaling required for cerebellar network development, including our recent study suggesting the importance of unbiased synaptic inputs from parallel fibers.MicroRNA-9-5p (miRNA-9-5p) is an important regulator of angiogenesis in many pathological states. However, the effect of miRNA-9-5p on angiogenesis after traumatic brain injury (TBI) has not been elucidated. In this study, a controlled cortical impact (CCI) model was used to induce TBI in Sprague-Dawley rats, and an oxygen glucose deprivation (OGD) model was used to mimic the pathological state in vitro. Brain microvascular endothelial cells (BMECs) were extracted from immature rats. The results showed that the level of miRNA-9-5p was significantly increased in the traumatic foci after TBI, and the upregulation of miRNA9-5p promoted the recovery of neurological function. Moreover, the upregulation of miRNA-9-5p with miRNA agomir significantly increased the density of the microvascular and neurons around the traumatic foci in rats after TBI. The results of the in vitro experiments confirmed that the upregulation of miRNA-9-5p with a miRNA mimic improved cellular viability and alleviated cellular apoptosis. Dual luciferase reporter assay validated that miRNA-9-5p was a posttranscriptional modulator of Ptch-1.