Neuroscience
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Stroke is the largest contributor to global neurological disability-adjusted life-years, posing a huge economic and social burden to the world. Though pharmacological recanalization with recombinant tissue plasminogen activator and mechanical thrombectomy have greatly improved the prognosis of patients with ischemic stroke, clinically, there is still no effective treatment for the secondary injury caused by cerebral ischemia. In recent years, more and more evidences show that neuroinflammation plays a pivotal role in the pathogenesis and progression of ischemic cerebral injury. ⋯ To inhibit microglia-related neuroinflammation and promote neurological recovery after ischemic stroke, numerous biochemical agents, cellular therapies, and physical methods have been demonstrated to have therapeutic potentials. Though accumulating experimental evidences have demonstrated that targeting microglia is a promising approach in the treatment of ischemic stroke, the clinical progress is slow. Till now, no clinical study could provide convincing evidence that any biochemical or physical therapies could exert neuroprotective effect by specifically targeting microglia following ischemic stroke.
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Emerging evidence suggests that the coupling relating the structural connectivity (SC) of the brain to its functional connectivity (FC) exhibits remarkable changes during development, normal aging, and diseases. Although altered structural-functional connectivity couplings (SC-FC couplings) have been previously reported in schizophrenia patients, the alterations in SC-FC couplings of different illness stages of schizophrenia (SZ) remain largely unknown. In this study, we collected structural and resting-state functional MRI data from 73 normal controls (NCs), 61 first-episode (FeSZ) and 78 chronic (CSZ) schizophrenia patients. ⋯ At the node strength level, significant decreased SC-FC coupling strength was observed in the FeSZ patients compared to that of the NCs, and the coupling strength was positively correlated with negative PANSS scores. These results demonstrated divergent alterations of SC-FC couplings in FeSZ and CSZ patients. Our findings provide new insight into the neuropathological mechanisms underlying the developmental course of SZ.
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Previous studies have shown that alterations in autophagy-related proteins exist extensively after traumatic brain injury (TBI). However, whether autophagy is enhanced or suppressed by TBI remains controversial. In our study, a controlled cortical impact was used to establish a model of moderate TBI in rats. ⋯ Furthermore, chloroquine treatment reversed the beneficial effects of SAR405 by increasing the accumulation of autophagosomes. Finally, our data showed that autophagy inhibition by VPS34 gene knockout method attenuated cell death after TBI. Our findings indicate that impaired autophagosome degradation is involved in the pathological reaction after TBI, and the inhibition of autophagy contributes to attenuate neuronal cell death and functional defects.
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The thalamus is a brain region consisting of anatomical and functional connections between various spinal, subcortical, and cortical regions, which has a putative role in the clinical manifestation of Multiple System Atrophy (MSA). Previous stereological studies have reported significant anatomical alterations in diverse brain regions of MSA patients, including the cerebral cortex, basal ganglia and white matter, but no quantitative studies have examined the thalamus. To establish the extent of thalamic involvement, we applied stereological methods to estimate the total number of neurons and glial cells (oligodendrocytes, astrocytes and microglia) as well as the volume in two thalamic sub-regions, the mediodorsal nucleus (MDT) and the anterior principal nucleus (APn), in brains from ten MSA patients and 11 healthy control subjects. ⋯ Finally, we saw no group differences in the total number of oligodendrocytes. Our findings show a region-specific loss of thalamic neurons that occurs without loss of oligodendrocytes, whereas thalamic microgliosis seems to occur alongside astrogliosis. These pathological changes in the thalamus may contribute to the cognitive impairment seen in most patients with MSA.
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Brain-derived neurotrophic factor (BDNF), including mature BDNF (mBDNF) and precursor BDNF (proBDNF), plays a pivotal role in neuronal survival, synaptic plasticity and neurogenesis. However, the functional effect of the mBDNF/proBDNF ratio in haemorrhagic stroke remains unclear. ATP is a known mediator of BDNF production in neurons and glia. ⋯ Moreover, both P2X4R-shRNA and SB203580 could effectively abolish the effect of ATP injection on the levels of P2X4R and p-p38-MAPK and the mBDNF/proBDNF ratio. Together, these findings show that ATP stimulation contributes to functional recovery after cerebral haemorrhage and that neuroprotection induced by ATP administration in ICH rats is accompanied by a strong increase in the mBDNF/proBDNF ratio. Here, we also show a significant role of P2X4R-p38-MAPK signalling in the ATP-induced increase in the mBDNF/proBDNF ratio in ICH.