摘要
This study was conducted to evaluate how sterubin affects rotenone-induced Parkinson's disease (PD) in rats. A total of 24 rats were distributed into 4 equal groups: normal saline control and rotenone control were administered saline or rotenone (ROT), respectively, orally; sterubin 10 received ROT + sterubin 10 mg/kg po; and sterubin alone was administered to the test group (10 mg/kg). Rats of the normal saline and sterubin alone groups received sunflower oil injection (sc) daily, 1 h after receiving the treatments cited above, while rats of the other groups received rotenone injection (0.5 mg/kg, sc). The treatment was continued over the course of 28 days daily. On the 29th day, catalepsy and akinesia were assessed. The rats were then euthanized, and the brain was extracted for estimation of endogenous antioxidants (MDA: malondialdehyde, GSH: reduced glutathione, CAT: catalase, SOD: superoxide dismutase), nitrative (nitrite) stress markers, neuroinflammatory cytokines, and neurotransmitter levels and their metabolites (3,4-dihydroxyphenylacetic acid (DOPAC), dopamine (DA), norepinephrine (NE), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA)). Akinesia and catatonia caused by ROT reduced the levels of endogenous antioxidants (GSH, CAT, and SOD), elevated the MDA level, and altered the levels of nitrites, neurotransmitters, and their metabolites. Sterubin restored the neurobehavioral deficits, oxidative stress, and metabolites of altered neurotransmitters caused by ROT. Results demonstrated the anti-Parkinson's activities of sterubin in ROT-treated rats.
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Objective To explore the effect of scutellarin on lipopolysaccharide(LPS)induced neuroinflammation in BV-2 microglia cells.Methods BV-2 microglia were cultured and randomly divided into 6 groups:control group(Ctrl),cyclic GMP-AMP synthetase(cGAS)inhibitor RU320521 group(RU.521 group),LPS group,LPS+RU.521 group,LPS+scutellarin pretreatment group(LPS+S)and LPS+S+RU.521 group.The expressions of cGAS,stimulator of interferon gene(STING),nuclear factor kappa B(NF-κB),phosphorylated NF-κB(p-NF-κB),neuroinflammatory factors PYD domains-containing protein 3(NLRP3)and tumor necrosis factor α(TNF-α)in BV-2 microglia were detected by Western blotting and immunofluorescent double staining(n= 3).Results Western blotting and immunofluorescent double staining showed that compared with the control group,the expression of cGAS,STING,p-NF-κB,NLRP3 and TNF-α in BV-2 microglia increased significantly after LPS induction(P<0.05),while the expression of cGAS,STING,p-NF-κB,NLRP3 and TNF-α in LPS+S group were significantly lower than those in LPS group(P<0.05).Treatment with cGAS pathway inhibitor RU.521 showed similar effects as the pre-treatment group with scutellarin.In addition,the change of NF-κB in each group was not statistically significant(P>0.05).Conclusion Scutellarin inhibits the neuroinflammation mediated by BV-2 microglia cells,which may be related to cGAS-STING signaling pathway.
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Neuropathic pain(NP)is caused by leision or disease of the somatic sensory nervous system,and its pathological mechanism is complex,mainly related to abnormal neural structure and function.It is hard for existing treatment methods to obtain satisfactory results.With the deepening of the study of peroxisome proliferate activation receptor-γ(PPAR-γ),its role in neuroinflammation,oxidative stress,ion channels,mitochondrial function,neuroprotection and other aspects have been discovered succes-sively,PPAR-γ may be one new target for pain prevention and treatment.This paper reviews the role of PPAR-γ in NP and related mechanisms,in order to provide new thinking for the clinical treatment of NP.
摘要
Chronic pain has been a prominent public health issue in China for years,affecting over 30%of the population.The mechanism of chronic pain has always been a controversial and difficult topic of pain medicine research.The polarization of microglia inherent in the central nervous system when the external microenvironment changes and the subsequent neuroinflammatory response are critical in chronic pain.Microglia can polarize into pro-inflammatory M1 or anti-inflammatory M2 phenotypes during neuroin-flammatory reactions,exerting neurotoxic or neuroprotective effects in the nervous system,respectively.The aim of the article is proposed to provide an overview of the main mechanisms of microglial polarization and-how it might contribute to chronic pain.
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The incidence of dementia increased significantly in the context of an aging population,imposing a significant burden on the economy and society.Therefore,finding the specific mechanism underlying cognitive decline in aging is of paramount significance.Recently,the role of microglia in the initiation and progression of cognitive decline in aging has become a research hotspot.Microglia,the resident immune cells of CNS,play important roles in immunosurveillance,synaptic pruning,damage repair and maintaining immune homeostasis.However,microglia undergo a variety of changes in cell morphology,gene expression and functional status with aging.This article review the impact of normal aging on microglia and the role of microglia in the pathogenesis of cognitive decline in aging,to provide a novel strategy for slowing or preventing the onset of dementia.
摘要
Stroke is the main cause of disability in adults.With the progress of stroke diagnosis and treatment technology,the mortality rate of stroke patients has decreased significantly,but its incidence keeps increasing,and there is an increasing number of stroke survivors develop chronic neurological disorders.At present,there is no clear drug to promote functional repair after stroke.Several studies have shown that gut microbiota can improve stroke prognosis by regulating neuroactive molecules and immune cell functions,enhancing neural network plasticity,and reducing neuroinflammation.Based on a review of previous studies,this paper describes the mechanism of action of gut microbiota on neural network plasticity and neuroinflammation after stroke and its impact on functional recovery after stroke and explores its clinical value and feasibility in improving neurological dysfunction after stroke.
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Objective:To investigate the effect of minocycline on neuroinflammation of rats with post-traumatic stress disorder(PTSD).Methods:The rat model of PTSD was prepared by a single prolonged stress(SPS)method,and the rats were treated with minocycline(PTSD+Mino group)or normal saline(PTSD group)by gavage.The behavioral changes of rats were detected by light-dark box test.The expression of ionized calcium-binding adapter molecule 1(Iba-1)in hippocampus was detected by immunohistochemical staining.The contents of IL-1β and TNF-α in hippocampus were detected by ELISA,and the expression levels of IL-1β and TNF-α mRNA in hippocampus were detected by real-time RT-PCR(qRT-PCR).Results:After 3 days of SPS stimulation,the anxiety-like behavior of rats was obvious,the expression of Iba-1 in hippocampus was increased,and the contents of IL-1β and TNF-α in hippocampus were in-creased.Minocycline treatment significantly reduced anxiety-like behavior and decreased the expression of Iba-1 in the hippocampus of PTSD rats.Meanwhile,minocycline treatment also decreased the levels of IL-1β and TNF-α mRNA and protein in the hippocampus.Conclusion:Minocycline can improve the anxiety-like behavior of PTSD rats by inhibiting the activation of microglia.
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BACKGROUND:Patients with Alzheimer's disease mainly show cognitive and memory dysfunctions.Aerobic exercise can inhibit endoplasmic reticulum stress and improve cognitive function of the patients.However,whether aerobic exercise can inhibit endoplasmic reticulum stress dependent neuroinflammation is still unclear. OBJECTIVE:To explore the effect of aerobic exercise on neuroinflammation and cognitive impairment in a mouse model of Alzheimer's disease. METHODS:Fifty C57BL/6J wild-type male mouse mice were randomly divided into wild-type control and wild-type exercise groups,while another 50 APP/PS1 double transgenic male mice were randomly divided into Alzheimer's disease group and Alzheimer's disease exercise group,with 25 mice in each group.Mice in the wild-type exercise and Alzheimer's disease exercise groups received aerobic exercise training(treadmill training,45 min/d,12 m/min,5 d/wk,8 weeks in total).Mice in the wild-type control and Alzheimer's disease groups were placed on the quiet running platform.Morris water maze test was used to detect the cognitive ability of mice.Hematoxylin-eosin staining and Nissl staining were used to detect hippocampal tissue damage in mice.Thioflavin-S staining was used to detect β-amyloid content in hippocampal tissue.Immunohistochemistry was used to detect β-amyloid and p-Tau levels in hippocampal tissue.Immunofluorescence staining was used to detect the number of positive cells for neuroinflammation-related factors in hippocampal tissue.Western blot was used to detect p-IRE1,IRE1,p-PERK,PERK,ATF6,GRP78,Bip,Caspase-12,Iba-1,and GFAP protein levels. RESULTS AND CONCLUSION:Compared with the wild-type control group,escape latency was increased,the number of times they reached the previous platform and the time they stayed on the platform were decreased,β-amyloid and Tau levels,p-IRE1/IRE1,p-PERK/PERK,ATF6,GRP78,Bip,Caspase-12,Iba-1,and GFAP protein levels,Iba-1+,Iba-1+TNF-α+,Iba-1+IL-6+,Iba-1+IL-1β+,GFAP+,GFAP+TNF-α+,GFAP+IL-6+,GFAP+IL-1β+ positive cells in hippocampal tissue were increased,and Iba-1+IL-4+,Iba-1+IL-10+,GFAP+IL-4+,GFAP+IL-10+ positive cells were decreased in the Alzheimer's disease group(P＜0.05).Compared with Alzheimer's disease group,escape latency was decreased,the number of times they reached the previous platform and the time they stayed on the platform were increased,β-amyloid and Tau levels,p-IRE1/IRE1,p-PERK/PERK,ATF6,GRP78,Bip,Caspase-12,Iba-1,GFAP protein levels,Iba-1+,Iba-1+TNF-α+,Iba-1+IL-6+,Iba-1+IL-1β+,GFAP+,GFAP+TNF-α+,GFAP+IL-6+,and GFAP+IL-1β+ positive cells in hippocampal tissue were decreased,and Iba-1+IL-4+,Iba-1+IL-10+,GFAP+IL-4+,GFAP+IL-10+ positive cells were increased in the Alzheimer's disease exercise group(P＜0.05).To conclude,aerobic exercise can reduce cognitive impairment in Alzheimer's disease mice by inhibiting endoplasmic reticulum stress and neuroinflammation in hippocampal tissue.
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BACKGROUND:Long non-coding RNAs(lncRNAs),as important regulators of the inflammatory response,are involved in the immune-inflammation-brain crosstalk mechanism after ischemic stroke and have the potential to become a therapeutic agent for neurological dysfunction after ischemic stroke. OBJECTIVE:To analyze and summarize the molecular mechanism of lncRNA acting on glial cells involved in the neuroimmuno-inflammatory cascade response after ischemic stroke and the associated signaling pathways,pointing out that lncRNAs have the potential to regulate inflammation after ischemic stroke. METHODS:PubMed was searched using the search terms of"ischemic stroke,long non-coding RNA,neuroinflammation,immune function,signal pathway,microglia,astrocytes,oligodendrocyte,mechanism,"and 63 relevant documents were finally included for review. RESULTS AND CONCLUSION:In the early stage of ischemic stroke,the death of nerve cells due to ischemia and hypoxia activates the innate immune response of the brain,promoting the secretion of inflammatory factors and inducing blood-brain barrier damage and a series of inflammatory cascades responses.As an important pathogenesis factor in ischemic stroke,the neuroimmuno-inflammatory cascade has been proved to seriously affect the prognosis of patients with ischemic stroke,and it needs to be suppressed promptly in the early stage.Neuroinflammation after ischemic stroke usually induces abnormal expression of a large number of lncRNAs that mediate a series of neuro-immune-inflammatory crosstalk mechanisms through regulating the polarization of microglia,astrocytes and oligodendrocytes to exert post-stroke neuroprotective effects.LncRNAs,as important regulatory factors of the inflammatory response,inhibit the neuroimmuno-inflammatory cascade response after ischemic stroke through regulating nuclear factor-κB,lncRNA-miRNA-mRNA axis,Rho-ROCK,MAPK,AKT,ERK and other signaling pathways to effectively improve neurological impairment after ischemic stroke.Most of experimental studies on the interaction between lncRNAs and ischemic stroke are based on a middle cerebral artery occlusion model or a cerebral ischemia-reperfusion injury model,but no clinical trials have been conducted.Therefore,it remains to be further explored about whether lncRNAs can be safely applied in clinical practice.At present,there are many therapeutic drugs for the treatment of ischemic stroke,but there are relatively few studies on the application of lncRNAs,exosomes and other transplantation technologies for the treatment of ischemic stroke using tissue engineering technology,which need to be further explored.lncRNA has become an important target for the treatment of ischemic stroke with its relative stability and high specificity.In future studies,more types of inflammatory lncRNAs that function under ischemic-hypoxia conditions should continue to be explored,in order to provide new research directions for the treatment of neuroinflammation after ischemic stroke.
摘要
BACKGROUND:Exercise has been widely recognized in the prevention and treatment of diabetes.Aerobic exercise has become an important part of the treatment of type 1 diabetes.However,the effect of treadmill exercise on the metabolism and chronic neuroinflammation of type 1 diabetes in different sexes needs further discussion. OBJECTIVE:To study the effects of treadmill exercise on metabolism and chronic neuroinflammation in type 1 diabetes mice of different sexes. METHODS:Forty C57BL/6 mice were divided into male group and female group,with 20 mice in each group.Then,a diabetes model was established by continuous injection of streptozotocin at 80 mg/kg for 3 days.Ten rats from each group were randomly selected to perform 6-week treadmill exercise as the diabetes+exercise group and another 10 rats from each group were selected as the diabetes group.Serum sex hormones,liver tissue oxidative stress,brain tissue inflammatory factors,and liver pathology were detected,and Morris water maze was performed for the observation of behavioral changes in mice. RESULTS AND CONCLUSION:Compared with the diabetes group,the diabetes+exercise group delayed the rise of blood sugar in type 1 diabetes mice(P＜0.05)and showed a significant reduction in serum follicle-stimulating hormone,luteinizing hormone,liver superoxide dismutase,malondialdehyde,brain tumor necrosis factor α,interleukin-6 and interleukin-1β levels(P＜0.01),while serum estradiol,progesterone,estrogen,and liver glutathione peroxidase protein levels were significantly increased(P＜0.01,P＜0.05).Compared with male type 1 diabetes mice,female type 1 diabetes mice had significantly higher estradiol levels and lower luteinizing hormone levels(P＜0.05).Compared with the male diabetes+exercise group,the female diabetes+exercise group had lower liver glutathione peroxidase levels(P＜0.05).Compared with type 1 diabetes mice,the escape latency of exercise training mice was shorter(P＜0.01).In male mice,exercises significantly increased the time and platform crossing times of type 1 diabetes mice in the target quadrant(P＜0.01 or P＜0.05),while in female mice,exercises significantly increased the time of type 1 diabetes mice in the target quadrant(P＜0.05).Correlation analysis results showed that the levels of follicle-stimulating hormone,luteinizing hormone,progesterone,superoxide dismutase,malondialdehyde,tumor necrosis factor α,and interleukin-6 were positively correlated with the level of interleukin-1β(P＜0.05 or P＜0.01),whereas the levels of estradiol and progesterone were negatively correlated with the levels of superoxide dismutase,malondialdehyde,tumor necrosis factor α,interleukin-6 and interleukin-1β(P＜0.05 or P＜0.01).Overall,there are sex differences in the effects of treadmill exercise on metabolic indicators and chronic neuroinflammatory regulation in diabetes mice.Sex hormones are an important variable of treadmill exercise in the metabolic,inflammatory and cognitive responses in diabetes mice.
摘要
Objective:To observe the effect of early electroacupuncture intervention on the expression of TARDNA bind-ing protein 43(TDP-43)and HMGB1/RhoA signaling pathway in the cerebral cortex of amyotrophic lateral sclerosis(ALS)mice,and to explore the potential mechanism of early electroacupuncture intervention in im-proving motor function in ALS mice. Method:SOD1G93A gene phenotype mice were randomly divided into model group(SOD1G93A),acupuncture in-tervention group(EA),riluzole group(Riluzole),and SOD1G93A negative mice in the same litter were blank control group(Control),with 15 mice in each group.The electroacupuncture group was given acupuncture of Baihui point,bilateral Tianzhu point,bilateral Tianshu point,5 times/7 days,7 days for a course of treat-ment,a total of 4 courses of treatment.The riluzole group was treated with riluzole 30 mg/(kg·d)by gavage,once a day,five times a week for two weeks.The motor function of mice in each group was evaluated by hind limb functional neurological score and rotarod fatigue test,and the rate of TDP-43 positive cells in cere-bral cortex was observed by immunofluorescence.The relative expression of Iba-1,HMGB1 or RhoA protein in cerebral cortex was detected by Western Blot.The levels of serum TNF-α and MCP-1 were detected by Elisa.The morphological changes of cerebral cortical neurons were observed by transmission electron microscopy. Result:Compared with the control group,the rotarod latency time was decreased and the neurological score was increased in the model group(P＜0.01).The contents of serum MCP-1 and TNF-α,the expression of Iba-1,HMGB1 and RhoA protein in cerebral cortex and the rate of TDP-43 positive cells were increased in the model group(P＜0.01).Compared with the model group,the rotarod latency time of the electroacupuncture group and the riluzole group increased and the neurological score decreased(P＜0.01,P＜0.05),the serum MCP-1,TNF-α content and the cerebral cortex Iba-1,HMGB1,RhoA protein expression and TDP-43 positive cell rate decreased(P＜0.01,P＜0.05).The results of electron microscopy showed that the structure of cortical neurons in the control group was normal,and the nerve cells in the model group exhibited obvious pathologi-cal changes.The damage of nerve cells in the electroacupuncture group and the riluzole group was reduced,the structure was relatively complete,and some normal organelles were detected. Conclusion:Electroacupuncture intervention can improve the motor function of ALS model mice.The mecha-nism may be related to the inhibition of HMGBl/RhoA signaling pathway and the reduction of microglia-in-duced neuroinflammation,and it is speculated that it has a positive effect on the reduction of ALS pathologi-cal substrate TDP-43 deposition.
摘要
PD is a neurodegenerative disease characterized by degenerative death of dopaminergic neurons in the substantia nigra,exhibiting a range of motor and non-motor symptoms with serious effects on quality of life.circRNA is a covalently closed-loop non-coding RNA that plays a major role in PD progression.This article reviews the involvement of circRNA in oxidative stress,regulation of transcription,neuroinflammation,autophagy,and α-synuclein.
摘要
Parkinson disease (PD) is a common chronic neurodegenerative disease that seriously affects the quality of life of patients and has become an important population health problem in society.The typical neuropathological feature of PD is the abnormal aggregation of α-synuclein (α-Syn) in the substantia nigra-striatal region, causing dopaminergic degenerative necrosis of neurons. With further research, it was found that cellular autophagy mediated the clearance process of pathological α-Syn involved in the pathogenesis of PD. Autophagy is an important pathway for cells to remove abnormal aggregated proteins and senescence-damaged organelles, and autophagic removal of abnormal α-Syn deposition can maintain cellular homeostasis and protect dopaminergic neurons. In addition, impaired autophagy causes α-Syn aggregation, increases α-Syn propagation in the brain, promotes the degeneration of dopaminergic neurons, and is involved in the development of PD.PD-related genes affect autophagy regulation, and mutations in related genes can lead to impaired lysosomal function to block autophagy. At the same time, abnormal aggregation of α-Syn further disrupts the autophagy process, reduces the autophagic clearance capacity, and increases the accumulation of neurotoxicity. Impaired autophagy and abnormal α-Syn aggregation are important mechanisms of degeneration in nigrostriatal dopaminergic neurons. Therefore, studies targeting autophagy and abnormal α-Syn aggregation may provide new ideas for the pathogenesis of PD, and reducing α-Syn accumulation by increasing autophagic flux may become a key target for the treatment of PD.
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Major depressive disorder (MDD) has become an increasingly serious public health issue, characterized by high incidence and high disability rates. It often coexists with other mental health problems and physical diseases, with a significant negative impact on patients' quality of life. In clinical practice, MDD is considered a heterogeneous disease. The complexity of the pathological mechanisms and the variability in treatment responses lead to a lack of clear therapeutic targets, which complicates the treatment process. In recent years, with advancements in neuroscience, the crucial role of microglia in the pathogenesis of MDD has been revealed. As the main immune cells in the brain, microglia are not only involved in the regulation of neuroinflammation but also play important roles in neurogenesis and neuronal regulation in MDD. This article mainly discusses the role of microglia in the pathophysiological mechanisms of MDD, aiming to provide a theoretical basis for microglia as a potential target for the treatment of MDD.
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Objective To observe the effects of electroacupuncture on post-stroke spasticity(PSS)rats and the relationship between microglia polarization-mediated neuroinflammation and neurotransmitter glutamate(Glu)and γ-aminobutyric acid(GABA)in cerebral cortex;To investigate the possible mechanism of electroacupuncture to relieve PSS.Methods Male SD rats were randomly divided into sham-operation group,model group and electroacupuncture group,with 10 rats in each group.A rat model of PSS was prepared using suture method combined with internal capsule injection of NMDA receptor.The electroacupuncture group selected"Quchi"and"Yanglingquan"electroacupuncture for 30 minutes per day,for 7 days,the model group and the sham-operation group were fixed at the same time without intervention.Zea Longa neurological function score and modified Ashworth muscular tone score were evaluated,and electrophysiology was tested;kits were used to GABA,Glu,tumor necrosis factor-α(TNF-α)and interleukin-10(IL-10)content in ischemic cortex;Western blot was used to detect the expression of GABRA1 and GAD67 protein in ischemic cortex;The co-expression of ionized calcium-binding protein 1(Iba-1),inducible nitric oxide synthase(iNOS)and Arg-1 were detected by immunofluorescence staining.Results Compared with the sham-operation group,the neurological function score and muscle tone score of the model group rats significantly increased(P<0.01),and muscle tone significantly increased(P<0.01);the contents of GABA and IL-10 in ischemic cortex significantly decreased(P<0.01),and the contents of TNF-α and Glu significantly increased(P<0.01),Glu/GABA ratio increased(P<0.01),GABRA1 and GAD67 protein expression significantly decreased(P<0.01),the co-expression of Iba-1 and iNOS significantly increased(P<0.01),while the co-expression of Iba-1 and Arg-1 was significantly decreased(P<0.01).Compared with the model group,the nerve function score and muscle tone score of the electroacupuncture group rats were significantly reduced(P<0.05),and muscle tone was significantly reduced(P<0.01);the contents of GABA and IL-10 in ischemic cortex significantly increased(P<0.01),and the contents of TNF-α and Glu significantly decreased(P<0.01),Glu/GABA ratio decreased(P<0.01),the protein expressions of GABRA1 and GAD67 significantly increased(P<0.01),the co-expression of Iba-1 and iNOS significantly decreased(P<0.01),while the co-expression of Iba-1 and Arg-1 significantly increased(P<0.05).Conclusion Electroacupuncture can effectively alleviate PSS,and its mechanism of action may be related to electroacupuncture regulating microglia polarization and reduing neuroinflammation.
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AIM To explore the effects of Shiquan Dabu Decoction on the synaptic function and cognitive impairment in a mouse model of Alzheimer's disease(AD).METHODS Sixty mice were randomly divided into the control group,the model group,the memantine group(5 mg/kg)and the high,medium and low dose Shiquan Dabu Decoction groups(6.24,3.12 and 1.56 g/kg),with 10 mice in each group.Except for those of the control group,the mice of other groups underwent their 70-day AD models induction by intraperitoneal injection of D-galactose and gavage feeding of AlCl3,followed by 42-day corresponding dosing of drugs by gavage on the 29th day.The mice had their spatial learning and associative memory detected by Morris water maze test and conditioned fear test;their morphological changes of hippocampal neurons observed by HE staining;their serum SOD activity,MDA level,and SOD,AChE activities and MDA,ACh,TNF-α and IL-1β levels in hippocampus detected by kits;and their PSD-95,Shank3,NR1,NR2A,NR2B,AMPK and p-AMPK protein expressions in hippocampus detected by Western blot.RESULTS Compared with the model group,the high-dose Shiquan Dabu Decoction group displayed improved spatial learning and memory ability and associative memory(P<0.05,P<0.01);reduced pathological damage of hippocampal neurons,decreased levels of oxidative stress and inflammation(P<0.05,P<0.01);enhanced cholinergic transmission(P<0.05,P<0.01),and increased protein expressions of PSD-95,Shank3,NR1,NR2A,NR2B,and p-AMPK in hippocampal tissue(P<0.05,P<0.01).CONCLUSION Shiquan Dabu Decoction can improve the cognitive impairment of in the mouse model of AD,and its mechanism may be related to AMPK activation and synaptic function restoration.
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Objective:To investigate the effect of low-dose ketamine on neuroinflammation and microcirculation in mice with traumatic brain injury (TBI).Methods:Sixty adult male C57BL/6 mice, weighing 22-28 g, were randomly divided into sham-operated group, TBI group, Sham+ketamine group, and TBI+ketamine group ( n=15). A controlled cortical impingement (CCI) method was used to establish TBI models in the later 2 groups. Sham+ketamine group and TBI+ketamine group were intraperitoneally injected with 30 mg/kg ketamine once daily for 3 d at 30 min after TBI; sham-operated group and TBI group were intraperitoneally injected same amount of saline at the same time points. Cerebral cortical blood flow in 6 mice from each group was measured by laser speckle contrast imaging (LSCI) before, immediately after, 30 min after, 1 d after and 3 d after modeling, respectively. Three d after modeling, immunohistochemical staining and immunofluorescent double label staining were used to detect the nuclear translocation of microglia markers, ionized calcin-antibody-1 (Iba-1) and nuclear factor (NF)-κB p65 in damaged cortical brain tissues in 6 mice from each group. The remaining 3 mice in each group were sacrificed and tissue plasma was extracted 3 d after modeling; levels of NF-κB p65, phosphorylated (p)-NF-κB p65, p-IκB and inducible nitric oxide synthase (iNOS) in cortical brain tissues were detected by Western blotting. Expressions of tumor necrosis factor-α (TNF-α), interleukin-1-β (IL-1β) and interleukin-6 (IL-6), iNOS, reactive oxygen species (ROS) and reactive nitrogen species (RNS) in cortical brain tissues were detected by ELISA. Results:LSCI indicated that, 3 d after modeling, relative blood flow in local cerebral microcirculation of TBI+ketamine group was significantly increased compared with that of TBI group ( P<0.05). Immunohistochemical staining indicated that compared with the sham-operated group and Sham+ketamine group, the TBI group and TBI+ketamine group had significantly increased number of Iba-1 positive cells in the cerebral cortex ( P<0.05); compared with the TBI group, the TBI+ketamine group had significantly decreased number of Iba-1 positive cells ( P<0.05). ELISA indicated that compared with the sham-operated group and Sham+ketamine group, the TBI group and TBI+ketamine group had significantly increased expressions of TNF-α, IL-1β, IL-6, iNOS, ROS and RNS in damaged cortical brain tissues ( P<0.05); compared with the TBI group, the TBI+ ketamine group had significantly decreased expressions of TNF-α, IL-1β, IL-6, iNOS, ROS and RNS in damaged cortical brain tissues ( P<0.05). Immunofluorescent double label staining indicated obviously inhibited NF-κB p65 nuclear translocation in TBI+ketamine group when it was compared with TBI group. Western blotting indicated that compared with the sham-operated group and Sham+ketamine group, the TBI+ketamine group had significantly increased iNOS, NF-κB p65, p-NF-κB p65 and P-IκB protein expressions in damaged cortical brain tissues ( P<0.05); compared with the TBI group, the TBI+ketamine group had significantly decreased protein expressions of iNOS, NF-κB p65, p-NF-κB p65 and p-IκB in damaged cortical brain tissues ( P<0.05). Conclusion:Low-dose ketamine reduces neuroinflammation and improves cerebral microcirculatory blood flow after open TBI, whose mechanism may be related to inhibition of microglia NF-κB/iNOS pathway.
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Objective @#To investigate the protective effects and mechanisms of soybean phospholipid powder on nerve cells in vitro and rats neural tissues.@*Methods @#In the cell experiments , the cytotoxicity of soybean phospholipid powder with different concentrations on mouse microglia cells ( BV2 ) and rat adrenal pheochromocytoma (PC12) cells was ob served by cell counting kit⁃8( CCK⁃8) assay. The effect of soybean phospholipid powder on the NO level of BV2 cells was analyzed by NO determination experiment , and the synaptic growth of PC12 cells was observed under the microscope. In the animal experiment , the cognitive dysfunction of rat was simulated by scopol⁃ ocampal tissue morphology and nerve cell density of scopolamine model mice were ob served by hematoxylin ⁃eosin staining (HE) staining.@*Results @#Soybean phospholipid powder had no obvious cytotoxicity on BV2 cells and PC12 cells within the concentration of 1 000 μg/ml. Compared with the control group , the NO secretion of BV2 cells pretreated with soybean phospholipid powder significantly decreased (P < 0. 01) , and the neuronal synapse growth of PC12 cells significantly increased (P < 0. 01) . In comparison to the model group , soybean phospholipid powder significantly improved the learning and memory ability of scopolamine model rats (P < 0. 05) , reduced the neuronal damage in dentate gyrus (DG) , cornu ammonis3 (CA3) , cornu ammonis1 (CA1) areas of hippocampus , and increased the density of nerve cells (P < 0. 001) .@*Conclusion @#Soybean phospholipid powder can play a neuroprotective role by reducing neuroinflammation and promoting neuronal synapse growth at the cellular level , and improve the learning and memory ability of rats with cognitive impairment , reduce hippocampal tissue damage.
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Depression is a prevalent mental illness worldwide, its multifaceted pathogenesis is still in the exploratory stage. MicroRNA (miRNA), as a crucial epigenetic regulator, plays an important role in depression. miR-124 is one of the most abundant miRNAs in the central nervous system including neurons and microglia, and involved in various biological events like neuron development and differentiation, synaptic and axonal growth, neural plasticity, inflammation and autophagy. Recent studies have reported abnormal expression of miR-124 in both depression patients and animal models. Most of the studies showed that miR-124 is upregulated in the hippocampus or prefrontal cortex in stress-induced rodent depression animal models such as CUMS, CSDS, CORT, CRS and LH but some evidence for divergence. Upregulation of miR-124 expression may be involved in depression-like behavior via CREB/BDNF/TrkB pathway, GR pathway, SIRT1 pathway, apoptosis and autophagy pathways by directly targeting these genes including Creb, Bdnf, Sirt1, Nr3c1, Ezh2 and Stat3. The downregulation of miR-124 expression in neurons is mainly involved in the neurogenesis and neuroplasticity impairments in depression by targeting the Notch signaling pathway and DDIT4/TSC1/2/mTORC1 pathway. The downregulation of miR-124 expression also was found in the activated microglia in the stress-induced models, and resulted in neuroinflammation. In summary, the abnormal expression of miR-124 in the brain of depression-related models and its related mechanisms are complex and even contradictory, and still need further research. This review provides a summary of the research progress of miR-124 in depression.
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I report five cases in which chikujountanto and untanto were effective for trauma and stressor-related disorders. Post-traumatic stress disorder (PTSD) and acute stress disorder (ASD) are both psychiatric disorders that occur as a reaction to severe stress, and are distinguished by the duration of the disorder. Chikujountanto is indicated for those who have cough and insomnia after late yang stage pattern in case of cold, and for chronic diseases such as depression and sleep disorders, and is applied to various psychiatric disorders. In this paper, I cite the grounds for applying chikujountanto to PTSD from the classics, examine the similarities and differences with other Kampo medicines reported to be used for PTSD from the characteristics of the constituent crude drug centered on Huang lian. I also infer the relationship between the therapeutic mechanism of Kampo and neuroinflammation. Regardless of the severity of the trauma, rapid administration of this drug is expected to hasten the healing process.