Recent studies have revealed that lipid droplets accumulate in neurons after brain injury and evoke lipotoxicity,damaging the neurons.However,how lipids are metabolized by spinal cord neurons after spinal cord injury ...Recent studies have revealed that lipid droplets accumulate in neurons after brain injury and evoke lipotoxicity,damaging the neurons.However,how lipids are metabolized by spinal cord neurons after spinal cord injury remains unclear.Herein,we investigated lipid metabolism by spinal cord neurons after spinal cord injury and identified lipid-lowering compounds to treat spinal cord injury.We found that lipid droplets accumulated in perilesional spinal cord neurons after spinal cord injury in mice.Lipid droplet accumulation could be induced by myelin debris in HT22 cells.Myelin debris degradation by phospholipase led to massive free fatty acid production,which increased lipid droplet synthesis,β-oxidation,and oxidative phosphorylation.Excessive oxidative phosphorylation increased reactive oxygen species generation,which led to increased lipid peroxidation and HT22 cell apoptosis.Bromocriptine was identified as a lipid-lowering compound that inhibited phosphorylation of cytosolic phospholipase A2 by reducing the phosphorylation of extracellular signal-regulated kinases 1/2 in the mitogen-activated protein kinase pathway,thereby inhibiting myelin debris degradation by cytosolic phospholipase A2 and alleviating lipid droplet accumulation in myelin debris-treated HT22 cells.Motor function,lipid droplet accumulation in spinal cord neurons and neuronal survival were all improved in bromocriptine-treated mice after spinal cord injury.The results suggest that bromocriptine can protect neurons from lipotoxic damage after spinal cord injury via the extracellular signal-regulated kinases 1/2-cytosolic phospholipase A2 pathway.展开更多
AIM:To evaluate the predictive value of superficial retinal capillary plexus(SRCP)and radial peripapillary capillary(RPC)for visual field recovery after optic cross decompression and compare them with peripapillary ne...AIM:To evaluate the predictive value of superficial retinal capillary plexus(SRCP)and radial peripapillary capillary(RPC)for visual field recovery after optic cross decompression and compare them with peripapillary nerve fiber layer(pRNFL)and ganglion cell complex(GCC).METHODS:This prospective longitudinal observational study included patients with chiasmal compression due to sellar region mass scheduled for decompressive surgery.Generalized estimating equations were used to compare retinal vessel density and retinal layer thickness preand post-operatively and with healthy controls.Logistic regression models were used to assess the relationship between preoperative GCC,pRNFL,SRCP,and RPC parameters and visual field recovery after surgery.RESULTS:The study included 43 eyes of 24 patients and 48 eyes of 24 healthy controls.Preoperative RPC and SRCP vessel density and pRNFL and GCC thickness were lower than healthy controls and higher than postoperative values.The best predictive GCC and pRNFL models were based on the superior GCC[area under the curve(AUC)=0.866]and the tempo-inferior pRNFL(AUC=0.824),and the best predictive SRCP and RPC models were based on the nasal SRCP(AUC=0.718)and tempo-inferior RPC(AUC=0.825).There was no statistical difference in the predictive value of the superior GCC,tempo-inferior pRNFL,and tempo-inferior RPC(all P>0.05).CONCLUSION:Compression of the optic chiasm by tumors in the saddle area can reduce retinal thickness and blood perfusion.This reduction persists despite the recovery of the visual field after decompression surgery.GCC,pRNFL,and RPC can be used as sensitive predictors of visual field recovery after decompression surgery.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82071376(to ZC)and 82001471(to CJ)the Natural Science Foundation of Shanghai,No.20ZR1410500(to ZC).
文摘Recent studies have revealed that lipid droplets accumulate in neurons after brain injury and evoke lipotoxicity,damaging the neurons.However,how lipids are metabolized by spinal cord neurons after spinal cord injury remains unclear.Herein,we investigated lipid metabolism by spinal cord neurons after spinal cord injury and identified lipid-lowering compounds to treat spinal cord injury.We found that lipid droplets accumulated in perilesional spinal cord neurons after spinal cord injury in mice.Lipid droplet accumulation could be induced by myelin debris in HT22 cells.Myelin debris degradation by phospholipase led to massive free fatty acid production,which increased lipid droplet synthesis,β-oxidation,and oxidative phosphorylation.Excessive oxidative phosphorylation increased reactive oxygen species generation,which led to increased lipid peroxidation and HT22 cell apoptosis.Bromocriptine was identified as a lipid-lowering compound that inhibited phosphorylation of cytosolic phospholipase A2 by reducing the phosphorylation of extracellular signal-regulated kinases 1/2 in the mitogen-activated protein kinase pathway,thereby inhibiting myelin debris degradation by cytosolic phospholipase A2 and alleviating lipid droplet accumulation in myelin debris-treated HT22 cells.Motor function,lipid droplet accumulation in spinal cord neurons and neuronal survival were all improved in bromocriptine-treated mice after spinal cord injury.The results suggest that bromocriptine can protect neurons from lipotoxic damage after spinal cord injury via the extracellular signal-regulated kinases 1/2-cytosolic phospholipase A2 pathway.
文摘AIM:To evaluate the predictive value of superficial retinal capillary plexus(SRCP)and radial peripapillary capillary(RPC)for visual field recovery after optic cross decompression and compare them with peripapillary nerve fiber layer(pRNFL)and ganglion cell complex(GCC).METHODS:This prospective longitudinal observational study included patients with chiasmal compression due to sellar region mass scheduled for decompressive surgery.Generalized estimating equations were used to compare retinal vessel density and retinal layer thickness preand post-operatively and with healthy controls.Logistic regression models were used to assess the relationship between preoperative GCC,pRNFL,SRCP,and RPC parameters and visual field recovery after surgery.RESULTS:The study included 43 eyes of 24 patients and 48 eyes of 24 healthy controls.Preoperative RPC and SRCP vessel density and pRNFL and GCC thickness were lower than healthy controls and higher than postoperative values.The best predictive GCC and pRNFL models were based on the superior GCC[area under the curve(AUC)=0.866]and the tempo-inferior pRNFL(AUC=0.824),and the best predictive SRCP and RPC models were based on the nasal SRCP(AUC=0.718)and tempo-inferior RPC(AUC=0.825).There was no statistical difference in the predictive value of the superior GCC,tempo-inferior pRNFL,and tempo-inferior RPC(all P>0.05).CONCLUSION:Compression of the optic chiasm by tumors in the saddle area can reduce retinal thickness and blood perfusion.This reduction persists despite the recovery of the visual field after decompression surgery.GCC,pRNFL,and RPC can be used as sensitive predictors of visual field recovery after decompression surgery.
