Neuroscience
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Clinical investigations to date have proposed the possibility that exposure to anesthetics is associated with neurodevelopmental deficits. Sevoflurane is the most commonly used general anesthetic in pediatric patients. Animal studies have demonstrated that multiple exposures to sevoflurane during the postnatal period resulted in neuropathological brain changes and long-term cognitive deficits. ⋯ The males had 35 hypermethylated genes, and some physiological processes related to the regulation of synaptic structure were enriched. Rhesus macaques are genetically closer to human beings. Our findings can help in the study of the mechanism of sevoflurane-relevant neurodevelopmental deficits at the posttranscriptional level and can provide new insights into potential clinical preventions and interventions for the neurotoxicity of neonatal anesthesia exposure.
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Parvalbumin-expressing (PV+) interneurons in the sensory cortex form powerful inhibitory synapses on the perisomatic compartments and axon initial segments of excitatory principal neurons (PNs), and perform diverse computational functions. Impaired PV+ interneuron functions have been reported in neural developmental and degenerative disorders. Expression of the unique marker parvalbumin (PV) is often used as a proxy of PV+ interneuron functions. ⋯ The expression of KV3.1 was correlated with spike frequency adaptation, but not with the expression of GAD67. These results suggest separate transcriptional regulations of PV/GAD67 vs. KV3.1, both of which are modulated by NIHL.
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Delayed paralysis occurs within some patients suffered from ischemic spinal cord injury (ISCI) due to the aorta occlusion during the repair surgery of thoracic and thoracoabdominal aortic aneurysms. Although mild hypothermia has been reported to improve ISCI and prolong the tolerance of rats to ISCI without inducing immediate paralysis, the mechanism remains unclear. Herein, the study revealed that the mild hypothermia treatment indeed partially improved the ISCI in rats caused by cross-clamping at the descending aorta. ⋯ In both in vivo ISCI model in rats and in vitro OGD model in BV-2 cells, the PI3K/AKT/mTOR pathway showed to be inhibited, whereas the PI3K/AKT/mTOR pathway was further inhibited by mild hypothermia in ISCI rats or rapamycin treatment in OGD-stimulated BV-2 cells. In conclusion, enhanced autophagy might be the mechanism of inhibited microglia activation by hypothermia treatment in ISCI rats and by rapamycin treatment in OGD-stimulated BV-2 cells. Autophagy could be enhanced through inhibiting the PI3K/AKT/mTOR pathway.
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Cerebral ischemia-reperfusion injury (IRI) is caused by reperfusion following ischemia. Mitophagy is closely related to cerebral IRI. Mitophagy disorder or excess may be harmful and lead to neuronal apoptosis. ⋯ Our research found that knockdown PRDX6 increased the expression of mitophagy-related and apoptosis-related proteins. Knocking down PINK1 relieved mitophagy and apoptosis caused by knocking down PRDX6. In conclusion, knockdown of PRDX6 could aggravate cerebral IRI by enhancing PINK1/PARKIN pathway mediated mitophagy, and this effect could increase neuronal apoptosis.
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Abundant findings including our previous work proved that the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome exerts a key role in the process of neuroinflammation following blast-induced traumatic brain injury (bTBI). The opening of potassium channels leads to low K+ environment in cells, which appears to be an essential requirement for NLRP3 inflammasome activation. Notably, MaxiK (BK) channel is significant for K+ transport. ⋯ In addition, paxilline could also decrease the level of pro-inflammatory cytokines and the biomarkers of brain injury and alleviate brain edema of bTBI rats. Our findings have revealed that MaxiK channel might be involved in the process of neuroinflammation of bTBI. Paxilline could depress neuro-inflammation response and alleviate brain injury by blocking MaxiK channel and subsequently inhibition of NLRP3 inflammasome activation.