OBJECTIVE Brain inflammation plays an important role in the pathophysiology of brain ischemicstroke,psychiatric and neurological diseases.During brain inflammation,microglia cells are activated and show pro-inflammato...OBJECTIVE Brain inflammation plays an important role in the pathophysiology of brain ischemicstroke,psychiatric and neurological diseases.During brain inflammation,microglia cells are activated and show pro-inflammatory M1 and anti-inflammatory M2 phenotypes,producing neurotoxic molecules and neurotrophic factors,respectively.We have previously discovered a novel natural product compound 3c exhibiting antiinflammatory effects in microglia cells,but the underlying mechanisms and its beneficial effects on brain inflammation and brain ischemia are unknown.METHODS The gene expression of M1 markers and M2 markers was measured by RT-PCR.The AMPK phosphorylation level and M2 marker CD206 protein expression were determined by Western blotting.TNFαrelease was measured by ELISA.The gene knowdown was performed by the si RNA transfection experiment.The LPS-induced brain inflammation mouse model and transient middle cerebral artery occlusion(t MCAO)stroke model were used.RESULTS We found that compound 3c inhibited M1polarization and promoted M2 polarization in LPS-stimulated BV2 and primary microglia cells,and these effects are mediated by Ca MKKβ/AMPK/JNK signaling pathway.Furthermore,compound 3c prevented M1 gene expression and enhanced M2 gene expression in a mouse model of LPS-induced neuroinflammation,and reduced the LPS-induced sickness behavior.In addition,compound 3c significantly reduced infarct volume,improved the neurological deficit,and reduced neuroinflammation in rats with acute focal cerebral ischemia.CONCLUSION Our results indicate that natural product compound 3c suppresses microglia activation by promoting M2 polarization and may provide a novel therapeutic approach to treat brain ischemic stroke associated with enhanced brain inflammation.展开更多
In the past two decades,pain perception in the human brain has been studied with EEG/MEG brain topography and PET/fMRI neuroimaging techniques.A host of cortical and subcortical loci can be activated by various nocice...In the past two decades,pain perception in the human brain has been studied with EEG/MEG brain topography and PET/fMRI neuroimaging techniques.A host of cortical and subcortical loci can be activated by various nociceptive conditions.The activation in pain perception can be induced by physical(electrical,thermal,mechanical),chemical(capsacin,ascoric acid),psychological(anxiety,stress,nocebo) means,and pathological(e.g.migraine,neuropathic) diseases.This article deals mainly on the activation,but not modulation,of human pain in the brain.The brain areas identified are named pain representation,matrix,neuraxis,or signature.The sites are not uniformly isolated across various studies,but largely include a set of cores sites:thalamus and primary somatic area(SI),second somatic area(SII),insular cortex(IC),prefrontal cortex(PFC),cingulate,and parietal cortices.Other areas less reported and considered important in pain perception include brainstem,hippocampus,amygdala and supplementary motor area(SMA).The issues of pain perception basically encompass both the site and the mode of brain function.Although the site issue is delineared to a large degree,the mode issue has been much less explored.From the temporal dynamics,IC can be considered as the initial stage in genesis of pain perception as conscious suffering,the unique aversion in the human brain.展开更多
Parkinson’s disease (PD) is a debilitating neurological disorder that affects <span>the aged population globally. This study aimed to explore how oral- and in</span>traperitoneal-rotenone-induced PD alter...Parkinson’s disease (PD) is a debilitating neurological disorder that affects <span>the aged population globally. This study aimed to explore how oral- and in</span>traperitoneal-rotenone-induced PD alters brain urea levels, histopathology, and key Parkinsonism<span>-related genes in the striatum. Hematoxylin and eosin staining was performed for histopathology assessment and real-time polymerase chain reaction was performed for gene expression. Rotenone 3 mg/kg body weight (Rot-3-ip) for 21 days and rotenone 50 mg/kg body weight (Rot-50-po) for 28 days significantly (p < 0.05) altered alpha-synuclein and tyrosine hydroxylase protein expression and <i>Snca</i>, <i>Becn</i>1 and <i>Prkaa</i>1 gene expression in the striatum. Lewy bodies were visible in both Rot-3-ip and Rot-50-po rat brains. There were </span><span>contrasting features in brain and liver histopathology between the oral and</span><span> intraperitoneal rotenone treatment groups. However, there was no significant (p < 0.05) difference in the brain urea levels between intraperitoneal and oral rotenone treatment groups. The propagation of PD through oral and intraperitoneal rotenone</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:"">can have different impacts on the pathological sequence of events based on the molecular approach.展开更多
文摘OBJECTIVE Brain inflammation plays an important role in the pathophysiology of brain ischemicstroke,psychiatric and neurological diseases.During brain inflammation,microglia cells are activated and show pro-inflammatory M1 and anti-inflammatory M2 phenotypes,producing neurotoxic molecules and neurotrophic factors,respectively.We have previously discovered a novel natural product compound 3c exhibiting antiinflammatory effects in microglia cells,but the underlying mechanisms and its beneficial effects on brain inflammation and brain ischemia are unknown.METHODS The gene expression of M1 markers and M2 markers was measured by RT-PCR.The AMPK phosphorylation level and M2 marker CD206 protein expression were determined by Western blotting.TNFαrelease was measured by ELISA.The gene knowdown was performed by the si RNA transfection experiment.The LPS-induced brain inflammation mouse model and transient middle cerebral artery occlusion(t MCAO)stroke model were used.RESULTS We found that compound 3c inhibited M1polarization and promoted M2 polarization in LPS-stimulated BV2 and primary microglia cells,and these effects are mediated by Ca MKKβ/AMPK/JNK signaling pathway.Furthermore,compound 3c prevented M1 gene expression and enhanced M2 gene expression in a mouse model of LPS-induced neuroinflammation,and reduced the LPS-induced sickness behavior.In addition,compound 3c significantly reduced infarct volume,improved the neurological deficit,and reduced neuroinflammation in rats with acute focal cerebral ischemia.CONCLUSION Our results indicate that natural product compound 3c suppresses microglia activation by promoting M2 polarization and may provide a novel therapeutic approach to treat brain ischemic stroke associated with enhanced brain inflammation.
基金grants from the National Natural Science Foundation of China(No.30770691)Beijing Municipal Government for Advancement of Sciences and Capital Medical University for Innovation Awards
文摘In the past two decades,pain perception in the human brain has been studied with EEG/MEG brain topography and PET/fMRI neuroimaging techniques.A host of cortical and subcortical loci can be activated by various nociceptive conditions.The activation in pain perception can be induced by physical(electrical,thermal,mechanical),chemical(capsacin,ascoric acid),psychological(anxiety,stress,nocebo) means,and pathological(e.g.migraine,neuropathic) diseases.This article deals mainly on the activation,but not modulation,of human pain in the brain.The brain areas identified are named pain representation,matrix,neuraxis,or signature.The sites are not uniformly isolated across various studies,but largely include a set of cores sites:thalamus and primary somatic area(SI),second somatic area(SII),insular cortex(IC),prefrontal cortex(PFC),cingulate,and parietal cortices.Other areas less reported and considered important in pain perception include brainstem,hippocampus,amygdala and supplementary motor area(SMA).The issues of pain perception basically encompass both the site and the mode of brain function.Although the site issue is delineared to a large degree,the mode issue has been much less explored.From the temporal dynamics,IC can be considered as the initial stage in genesis of pain perception as conscious suffering,the unique aversion in the human brain.
文摘Parkinson’s disease (PD) is a debilitating neurological disorder that affects <span>the aged population globally. This study aimed to explore how oral- and in</span>traperitoneal-rotenone-induced PD alters brain urea levels, histopathology, and key Parkinsonism<span>-related genes in the striatum. Hematoxylin and eosin staining was performed for histopathology assessment and real-time polymerase chain reaction was performed for gene expression. Rotenone 3 mg/kg body weight (Rot-3-ip) for 21 days and rotenone 50 mg/kg body weight (Rot-50-po) for 28 days significantly (p < 0.05) altered alpha-synuclein and tyrosine hydroxylase protein expression and <i>Snca</i>, <i>Becn</i>1 and <i>Prkaa</i>1 gene expression in the striatum. Lewy bodies were visible in both Rot-3-ip and Rot-50-po rat brains. There were </span><span>contrasting features in brain and liver histopathology between the oral and</span><span> intraperitoneal rotenone treatment groups. However, there was no significant (p < 0.05) difference in the brain urea levels between intraperitoneal and oral rotenone treatment groups. The propagation of PD through oral and intraperitoneal rotenone</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:"">can have different impacts on the pathological sequence of events based on the molecular approach.
