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1.
International Eye Science ; (12): 53-56, 2022.
Article in Chinese | WPRIM | ID: wpr-906729

ABSTRACT

@#Microglial activation is one of the main pathogenic factors to cause retinal neuroinflammation. Recently, with the advancement of retinal imaging technologies, hyperreflective foci(HRF), as a novel biomarker in optical coherence tomography(OCT)imaging, have received more attention in retinal neuroinflammation. Current research demonstrated that HRF are the aggregates mainly derived from the activated microglia in retina or mononuclear phagocyte-macrophage from the blood. HRF were defined as discrete and well-circumscribed hyperreflective dot-shaped lesions with the maximum diameter between 20-50μm in retina and choroid imaged with OCT. Under pathological conditions, the number of HRF increases significantly. Under pathological condations, the number of HRF was obviously increased, which might be related to the severity of some retinal diseases. However, the research on the source and function of HRF is still in its infancy. This review is aimed to describe the basic characteristics of HRF and their roles in both retinal inflammatory diseases and neurodegenerative diseases of the central nervous system. HRF are expected to be a potential and novel biomarker of inflammation for early diagnosis and prognosis of neuroinflammation in both retinal and central nervous system diseases.

2.
Acta Pharmaceutica Sinica ; (12): 1946-1953, 2022.
Article in Chinese | WPRIM | ID: wpr-936567

ABSTRACT

Cell senescence is characterized by permanent cell cycle arrest, accompanied by the changes in cell metabolism and epigenetic regulation. Alzheimer's disease (AD) is a common neurodegenerative disease, with the main symptoms of memory loss and cognitive impairment. A large number of studies have shown that the senescence of central nervous system cells such as astrocytes and microglia is closely related to the occurrence of AD. Inhibition of brain cell senescence is expected to provide new ideas and therapeutic strategies for the prevention and treatment of AD. This paper reviews the potential roles and mechanisms of senescence of brain cells in AD, and interaction effects among brain cells. This review will provide a new direction for the study of pathological mechanism of AD and the development of anti-AD drugs.

3.
Article in Chinese | WPRIM | ID: wpr-936306

ABSTRACT

OBJECTIVE@#To investigate the inhibitory effect of ANA-12 that blocks brain-derived neurotrophic factor (BDNF)/ tropomyosin receptor kinase B (TrkB) signaling on inflammatory pain in rats and explore the underlying mechanism.@*METHODS@#Forty-two adult SD rats were randomized into BDNF-induced acute pain group (n=24) and CFA-induced chronic pain group. The former group were randomly divided into 4 subgroups, including a control group, ANA-12 treatment group, BDNF treatment group, and BDNF+ANA-12 treatment group; the latter group were subgrouped into control group, CFA treatment group (CFA) and CFA + ANA-12 treatment group. The effects of ANA-12 treatment on pain behaviors of the rats with BDNF-induced acute pain and CFA-induced chronic inflammatory pain were observed. Western blotting was used to examine TrkB signaling and expressions of microglia marker protein Iba1 and TNF-α in the spinal cord of the rats.@*RESULTS@#BDNF injection into the subarachnoid space significantly increased the number of spontaneous paw withdrawal of the rats (P < 0.05), which was obviously reduced by ANA-12 treatment (P < 0.05). The rats with intraplantar injection of CFA, showed significantly increased ipsilateral mechanical stimulation sensitivity (P < 0.05), and ANA-12 treatment obviously increased the ipsilateral foot withdrawal threshold (P < 0.05). Treatment with either BDNF or CFA significantly increased the phosphorylation level of TrkB (Y705) in the spinal cord of the rats (P < 0.05), which was significantly lowered by ANA-12 treatment (P < 0.05). Treatment with BDNF and CFA both significantly up-regulated the expressions of Iba1 and TNF-α in the spinal cord (P < 0.05), but ANA-12 significantly reduced their expression levels (P < 0.05).@*CONCLUSION@#ANA-12 can reduce spinal cord inflammation and relieve acute and chronic pain in rats by targeted blocking of BDNF/TrkB signaling.


Subject(s)
Animals , Brain-Derived Neurotrophic Factor/metabolism , Chronic Pain/drug therapy , Inflammation , Rats , Rats, Sprague-Dawley , Receptor, trkB/metabolism
4.
Article in English | WPRIM | ID: wpr-928988

ABSTRACT

OBJECTIVES@#During pregnancy, pregnant women are prone to stress reactions due to external stimuli, affecting their own health and fetal development. At present, there is no good treatment for the stress reactions from pregnant women during pregnancy. This study aims to explore the effect of probiotics on abnormal behavior and hippocampal injury in pregnant stressed offspring.@*METHODS@#SD pregnant rats were divided into a control group, a stress group, and a probiotics group, with 6 rats in each group. The control group was untreated; the stress group was given restraint stress on the 15th-20th day of pregnancy; the probiotics group was given both bifidobacterium trisporus capsules and restraint stress on the 15th-20th day of pregnancy, and the offspring continued to be fed with probiotics until 60 days after birth (P60). The offspring rats completed behavioral tests such as the open field test, the elevated plus maze test, the new object recognition test, and the barnes maze test at 60-70 d postnatally. Nissl's staining was used to reflect the injury of hippocampal neurons; immunohistochemical staining was used to detect the expression of microglia marker ionized calcium binding adapter molecule 1 (IBA-1) which can reflect microglia activation; ELISA was used to detect the content of plasma TNF-α and IL-1β; Western blotting was used to detect the expression of Bax, Bcl-2, and caspase-3.@*RESULTS@#The retention time of offspring rats in the stress group in the central area of the open field was significantly less than that in the control group (P<0.01), and the retention time of offspring rats in the probiotic group in the central area of the open field was significantly more than that in the stress group (P<0.05). The offspring rats in the stress group stayed in the open arm for a shorter time than the control group (P<0.05) and entered the open arm less often than the control group (P<0.01); the offspring rats in the probiotic group stayed in the open arm for a longer time than the stress group and entered the open arm more often than the stress group (both P<0.05). The discrimination ratio for new to old objects in the offspring rats of the stress group was significantly lower than that of the control group (P<0.01), and the discrimination ratio for new to old objects in the offspring rats of the probiotic group was significantly higher than that of the stress group (P<0.05). The offspring rats in the stress group made significantly more mistakes than the control group (P<0.05), and the offspring rats in the probiotic group made significantly fewer mistakes than the stress group (P<0.05). Compared with the control group, the numbers of Nissl bodies in CA1, CA3, and DG area were significantly reduced in the offspring rats of the stress group (all P<0.001), the number of activated microglia in DG area of hippocampus was significantly increased (P<0.01), the contents of TNF-α and IL-1β in peripheral blood were significantly increased (P<0.05 or P<0.01), the protein expression level of Bcl-2 was significantly down-regulated, and the protein expression levels of Bax and caspase-3 were significantly up-regulated (all P<0.001). Compared with the stress group, the numbers of Nissl bodies in CA1, CA3, and DG area were significantly increased in the probiotic group offspring rats (P<0.001, P<0.01, P<0.05), the number of activated microglia in the DG area of hippocampus was significantly reduced (P<0.05), and the TNF-α and IL-1β levels in peripheral blood were significantly decreased (both P<0.05), the protein expression level of Bcl-2 was significantly up-regulated, and the protein expression levels of Bax and caspase-3 were significantly down-regulated (all P<0.001).@*CONCLUSIONS@#Probiotic intervention partially ameliorated anxiety and cognitive impairment in rats offspring of pregnancy stress, and the mechanism may be related to increasing the number of neurons, inhibiting the activation of hippocampal microglia, and reducing inflammation and apoptosis.


Subject(s)
Animals , Caspase 3/metabolism , Female , Hippocampus/physiopathology , Humans , Pregnancy , Probiotics/therapeutic use , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats , Stress, Psychological/therapy , Tumor Necrosis Factor-alpha/metabolism , bcl-2-Associated X Protein/metabolism
5.
Biol. Res ; 552022.
Article in English | LILACS-Express | LILACS | ID: biblio-1383914

ABSTRACT

Abstract Background: In Alzheimer's disease (AD), the neuroinflammatory response mediated by the activation of senescent microglia is closely related to energy dysmetabolism. However, the mechanism underlying the interaction between the energy metabolism of aging microglia and neuroinflammation remains unclear. Methods: We used biochemical methods, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and western blot to determine the effects and mechanism of CD38 knockdown on energy metabolism and neuroinflammation in Aβ1-40 injured BV2 cells. Using AD model mice, we detected CD38 enzyme activity, energy metabolism factors (ATP, NAD +, and NAD +/NADH), and neuroinflammatory factors (IL-1β, IL-6, and TNF-α) following the addition of CD38 inhibitor. Using a combination of biochemical analysis and behavioral testing, we analyzed the effects of the CD38 inhibitor on energy metabolism disorder, the neuroinflammatory response, and the cognition of AD mice. Results: Following Aβ1-40 injury, SA-β-Gal positive cells and senescence-related proteins P16 and P21 increased in BV2 cells, while energy-related molecules (ATP, NAD +, and NAD +/NADH) and mitochondrial function (mitochondrial ROS and MMP) decreased. Further studies showed that CD38 knockdown could improve Aβ1-40-induced BV2 cells energy dysmetabolism and reduce the levels of IL-1β, IL-6, and TNF-α. In vivo results showed an increase in senile plaque deposition and microglial activation in the hippocampus and cortex of 34-week-old APP/PS1 mice. Following treatment with the CD38 inhibitor, senile plaque deposition decreased, the number of Iba1 +BV2 cells increased, the energy metabolism disorder was improved, the proinflammatory cytokines were reduced, and the spatial learning ability was improved. Conclusions: Our results confirm that senescent microglia appeared in the brain of 34-week-old APP/PS1 mice, and that Aβ1-40 can induce senescence of BV2 cells. The expression of CD38 increases in senescent BV2 cells, resulting in energy metabolism disorder. Therefore, reducing CD38 expression can effectively improve energy metabolism disorder and reduce proinflammatory cytokines. Following intervention with the CD38 inhibitor in APP/PS1 mice, the energy metabolism disorder was improved in the hippocampus and cortex, the level of proinflammatory cytokines was reduced, and cognitive impairment was improved.

6.
Clinics ; 77: 100062, 2022. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1394294

ABSTRACT

Abstract Introduction: Short-Chain Fatty Acids (SCFA) are products of intestinal microbial metabolism that can reach the brain and alter microglia in health and disease contexts. However, data are conflicting on the effect of acetate, the most abundant SCFA in the blood, in these cells. Objective: The authors aimed to investigate acetate as a modulator of the inflammatory response in microglia stimulated with LPS. Method: The authors used an immortalized cell line, C8-B4, and primary cells for in vitro treatments with acetate and LPS. Cell viability was analyzed by MTT, cytokine by RT-PCR, ELISA, and flow cytometry. The authors also performed in vivo and in silico analyses to study the role of acetate and the TNF-α contribution to the development of Experimental Autoimmune Encephalomyelitis (EAE). Results: Acetate co-administered with LPS was able to exacerbate the production of pro-inflammatory cytokines at gene and protein levels in cell lines and primary culture of microglia. However, the same effects were not observed when acetate was administered alone or as pretreatment, prior to the LPS stimulus. Additionally, pharmacological inhibition of histone deacetylase concomitantly with acetate and LPS led to decreased TNF-α production. In silico analysis showed a crucial role of the TNF-α pathway in EAE development. Moreover, acetate administration in vivo during the initial phase of EAE led to a better disease outcome and reduced TNF-α production. Conclusion: Treatment with acetate was able to promote the production of TNF-α in a concomitant LPS stimulus of microglia. However, the immune modulation of microglia by acetate pretreatment may be a component in the generation of future therapies for neurodegenerative diseases. HIGHLIGHTS Acetate was able to exacerbate the production of TNF-α in microglia. Acetate administered as pre-treatment to LPS acts as an anti-inflammatory. Histone deacetylase decreased TNF-α production in Acetate- and LPS-treated cells. Depending on the time of administration, Acetate modulates microglia's activation. Acetate may threaten neurodegenerative and neuropsychiatric diseases.

7.
Chinese Journal of Neurology ; (12): 520-524, 2022.
Article in Chinese | WPRIM | ID: wpr-933819

ABSTRACT

At present, many drugs were developed based on the main pathological feature of Alzheimer′s disease (AD): "β-amyloid cascade hypothesis and abnormal tau protein aggregation" as targets, but the efficacy is unsatisfactory. With the progress on the study of pathological mechanism of AD, the role of microglia and their related expression genes, such as TREM2, CD 33, ABCA7 gene and their related signal transduction pathways in the pathological mechanism of AD has been paid more and more attention. The study on AD biomarkers and therapeutic targets based on microglia and their related expression genes has also increased significantly. This review will mainly focus on the pathophysiology of microglia, the mechanism of microglia in AD, the biomarkers related to microglia and the drug treatment of AD.

8.
Article in Chinese | WPRIM | ID: wpr-933328

ABSTRACT

Objective:To evaluate the effect of electrical stimulation on lipopolysaccharide (LPS)-induced activation of M1 microglia.Methods:The well-growing BV2 microglia cells were divided into 3 groups ( n=18 each) using a random number table method: control group (group C), group LPS, LPS and electrical stimulation group (group LE). The cells were cultured for 24 h in normal culture atmosphere in group C. In group LPS and group LE, the LPS medium culture 100 ng/ml was added, and the cells were cultured for 24 h. In group LE, cells were stimulated with 100 mV/mm direct current for 4 h before LPS incubation.The levels of tumor necrosis factor-α (TNF-α) and leukocyte interleukin-1β (IL-1β) were determined by enzyme-linked immunosorbent assay.The expression of the M1 microglia surface markers CD32 and inducible nitric oxide synase (iNOS) was detected using immunofluorescent staining.The expression of CD32 and iNOS mRNA was detected using quantitative real-time polymerase chain reaction. Results:Compared with group C, the concentrations of TNF-α and IL-1β were significantly increased, and the expression of CD32 and iNOS protein and mRNA was up-regulated in LPS and LE groups ( P<0.05). Compared with group LPS, the concentrations of TNF-α and IL-1β were significantly decreased, and the expression of CD32 and iNOS protein and mRNA was down-regulated in group LE ( P<0.05). Conclusions:Electrical stimulation can inhibit LPS-induced activation of M1 microglia and thus alleviate the inflammatory responses.

9.
Article in Chinese | WPRIM | ID: wpr-933297

ABSTRACT

Objective:To evaluate the effect of hepatic ischemia-reperfusion (I/R) rats-derived exosomes on microglial pyroptosis.Methods:Twenty clean-grade healthy male Sprague-Dawley rats, aged 2-3 weeks, weighing 20-50 g, were divided into 2 groups ( n=10 each) using a random number table method: sham operation group (group S) and hepatic I/R group (group I/R). The serum of rats in S group and I/R group was collected, and exosomes were isolated from the sera using differential centrifugations.Microglial cells were co-cultured with PKH26-labeled exosomes for 6 h. The intake of exosomes in microglial cells was determined using immunofluorescence staining.Primary microglial cells were seeded onto 6-well culture plates at a density of 5×10 5 cells/ml and were divided into 4 groups ( n=6 each) using a random number table method: control group (group C), 10 7 cells/ml I/R-exosomes treated group (group 10 7), 10 8 cells/ml I/R-exosomes treated group (group 10 8), and 10 9 cells/ml I/R-exosomes treated group (group 10 9). Microglia in each group were co-cultured with the corresponding concentration of I/R-exosomes for 6 h. The expression of NOD-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), cleaved-caspase-1 and gasdermin-D (GSDMD) was detected using Western blot.Primary microglial cells were divided into 3 groups ( n=24 each) by a random number table method: control group (group C), sham operation-exosomes treated group (group S-exosome) and I/R-exosomes treated group (group I/R-exosome). In S-exosome group and I/R-exosome group, exosomes 10 8 cells/ml in S group and I/R group were given, respectively, to incubate cells for 6 h. The expression of NLRP3, ASC and GSDMD mRNA was determined by real-time polymerase chain reaction, and the levels of interleukin-18 (IL-18), IL-1β and tumor necrosis factor-alpha (TNF-α) in the cell culture supernatant were measured by enzyme-linked immunosorbent assay. Results:The results from immunofluorescence staining showed that I/R-exosomes colocalized with microglia.The 10 8 cells/ml I/R-exosomes and 10 9 cells/ml I/R-exosomes up-regulated the expression of NLRP3, ASC, GSDMD and cleaved-caspase-1 in microglial cells ( P<0.01). Compared with group C and group S-exosome, the expression of NLRP3, ASC and GSDMD mRNA in microglial cells was up-regulated, and the levels of IL-18, IL-1β and TNF-α in the supernatant were elevated in group I/R-exosome ( P<0.01). Conclusions:Hepatic I/R rats-derived exosomes can promote microglial pyroptosis.

10.
Article in Chinese | WPRIM | ID: wpr-933294

ABSTRACT

Objective:To evaluate the effect of long-term intake of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) on the activation of hippocampal microglia in a mouse model of postoperative cognitive dysfunction (POCD).Methods:Ninety-six clean-grade healthy male C57BL/6 mice, aged 8 weeks, weighing 18-24 g, were stratified according to body weight and divided into 4 groups ( n=24 each) by a random number table method: control diet group (group C), ω-3 PUFAs group (group ω), control diet plus POCD group (group C+ P) and ω-3 PUFAs plus POCD group (group ω+ P). Mice were fed a special ω-3 PUFAs diet (DHA 0.14 g/100 g, EPA 0.03 g/100 g) for 12 weeks in group ω and group ω+ P, while mice were fed with a control diet for 12 weeks in group C and group C+ P.Tibial fracture procedures were performed under isoflurane anesthesia to develop the POCD model after 12 weeks of feeding.The fear conditioning test and Y maze test were performed on 1st and 3rd days after developing the model.The mice were sacrificed after behavioral tests, and the hippocampal tissues were removed for determination of the contents of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) (by gas chromatography-mass spectroscopy), density of Iba-1 positive microglia (by immunofluorescence staining), and expression of mature brain-derived neurotrophic factor (mBDNF) and precursor brain-derived neurotrophic factor (pro-BDNF) (by Western blot), and contents of interleukin-1beta (IL-1β) and interleukin-6 (IL-6) (by enzyme-linked immunosorbent assay). Results:Compared with group C, the contents of DHA and EPA were significantly increased, the percentage of freezing time in the contextual test was increased, mBDNF/pro-BDNF ratio was increased ( P<0.05), no significant change was found in the rotation accuracy in Y maze test, density of Iba-1 positive microglia and contents of IL-1β and IL-6 in hippocampus ( P>0.05) in group ω ( P<0.05), and no significant change was found in the contents of DHA and EPA ( P>0.05), the percentage of freezing time in the contextual test and accuracy of rotation in Y maze test were decreased on 1st and 3rd days after operation, the density of Iba-1 positive microglia and contents of IL-1β and IL-6 were increased, and mBDNF/pro-BDNF ratio was decreased in group C+ P ( P<0.05). Compared with group C+ P, the contents of DHA and EPA were significantly increased, the percentage of freezing time in the contextual test and accuracy of rotation in Y maze test were increased on 1st and 3rd days after operation, the density of Iba-1 positive microglia and contents of IL-1β and IL-6 were decreased, and mBDNF/pro-BDNF ratio was increased in group ω+ P ( P<0.05). Conclusions:Long-term intake of ω-3 PUFAs can improve cognitive function in a mouse model of POCD, and the mechanism may be related to inhibition of activation of hippocampal microglia, reduction of inflammatory responses, and thus increasing the mBDNF/Pro-BDNF ratio.

11.
Journal of Chinese Physician ; (12): 53-58, 2022.
Article in Chinese | WPRIM | ID: wpr-932025

ABSTRACT

Objective:To explore the efficacy of breaking blood expelling stasis method accelerates hematoma resolution after intracerebral hemorrhage (ICH) and its potential mechanism.Methods:63 ICH patients confirmed by computer tomography (CT) scan from August 2019 to February 2020 were selected as the research objects and randomly divided into control group ( n=29, routine treatment plus placebo) and observation group ( n=34, routine treatment plus breaking blood expelling stasis granules). The changes of neurological function and hematoma volume were observed before and after treatment. At the same time, the ICH rat model was constructed to observe the changes of neurobehavior and hematoma volume after the intervention of breaking blood expelling stasis granules. The expressions of peroxidase proliferator-activated-receptor γ(PPARγ), CD11b and CD36 in the surrounding tissues of hematoma were detected by Western blot on the third day after the intervention. Results:After two weeks of treatment, the National Institutes of Health Stroke Scale (NIHSS) score and hematoma volume of the two groups decreased (all P<0.05), and the NIHSS score and hematoma volume of the observation group were significantly lower than those of the control group (all P<0.05). In addition, the changes of NIHSS score and hematoma volume in the observation group before and after treatment were significantly greater than those in the control group ( P<0.01). In animal experiments, the hematoma volume in the breaking blood expelling stasis group on the 14th day after ICH was significantly smaller than that in the ICH group [(9.8±4.9)mm 3 vs (17.6±6.4)mm 3,P<0.05], and the reduction of hematoma in the breaking blood expelling stasis group on the 7th and 14th day was significantly larger than that in the ICH group [(4.6±2.9)mm 3 vs (-2.1±1.6)mm 3, (14.3±3.8)mm 3 vs (4.2±2.8)mm 3, all P<0.01]. The percentage of right turn on 3rd, 7th and 14th day and the modified Neurological Severity Score (mNSS) on 7th and 14th day in the breaking blood expelling stasis group were lower than those in the ICH group (all P<0.05). Western blot analysis showed that the expressions of CD11b, CD36 and PPARγ in the breaking blood expelling stasis group on the third day after ICH were significantly higher than those in the ICH group (CD11b: 0.78±0.12 vs 0.49±0.11, P<0.05; CD36: 1.16±0.16 vs 0.80±0.11, P<0.05; PPARγ: 0.78±0.11 vs 0.37±0.10, P<0.01). Conclusions:Breaking blood expelling stasis can effectively accelerate intracerebral hematoma clearance and improve neurological outcome after ICH, and the mechanism maybe probably mediated by activating PPARγ and enhanced CD36, CD11b upregulation on microglia/macrophages, which resulting in facilitating erythrocyte endogenous phagocytosis.

12.
Article in Chinese | WPRIM | ID: wpr-931938

ABSTRACT

Objective:To investigate the effect of activation of microglia in prefrontal cortex on long-term spatial memory in post-stroke depression mice.Methods:Forty-eight male C57BL/6 mice were divided into sham operation group, stroke group, post-stroke depression group and depression group according to the random number table method with 12 in each group, and 36 mice were divided into solvent group, enrofloxacin group and minocycline group according to the random number table method with 12 in each group.Middle cerebral artery occlusion (MCAO) was use to establish the stroke model, and forced swimming was used to establish the depression model.The post-stroke depression model mice were received MCAO first and then received forced swimming on the 4th day after stroke to establish the model.Mice in enrofloxacin group and minocycline group were treated with enrofloxacin and minocycline injection once a clay for 14 days from the 5th day after stroke, respectively.Forced swimming test and sugar water preference test were used to evaluate the depression of mice in each group, Morris water maze test was used to detect the spatial memory function of mice in each group, and Nissl staining and immunofluorescence staining were used to detect the neuronal function and the number and type of microglia activation.The expression of inflammatory cytokines IL-6 and IL-1β were detected by Western blot.GraphPad Prism 8.0.1 statistical software was used for statistical analysis.The single factor variance analysis was used to compare the difference among multiple groups, and pairwise comparison was performed with SNK- q test. Results:(1) There were statistically significant differences in depression, learning and memory, neuron damage, activation of microglia, inflammatory factors and other indicators in sham operation group, stroke group, post-stroke depression group and depression group ( F=43.58-255.70, all P<0.05). Compared with stroke group, post-stroke depression group had longer floating immobility time ((222.70±29.12) s, (79.25±46.78) s, P<0.05), the preference rate of sugar water was significantly lower ( (49.44±6.19) %, (84.49±4.73) %, P<0.05), and the average value of platform approach after correction was higher((125.00±9.95) mm, (96.79±12.57) mm, P<0.05), Nissl bodies expression was lower ((53.50±15.78) cells /mm 2, (85.67±17.52) cells /mm 2, P<0.05), NeuN positive expression rate was lower ((29.78±3.70) %, (45.73±4.51) %, P<0.05), the percent of M1 microglia expression was significantly higher ((75.55±8.84) %, (58.19±5.69) %, P<0.05), the percent of M2 microglia expression was lower ((43.46±5.11)%, (57.14±5.40)%, P<0.05), and the expression levels of IL-6 ((1.14±0.03), (0.94±0.05), P<0.05) and IL-1β((1.17±0.03), (0.56±0.04), P<0.05) were significantly higher.(2) Depression, learning and memory, neuron injury, activation of microglia, inflammatory factors and other indicators of mice in solvent group, enrofloxacin group and minocycline group were significantly different ( F=7.13-94.35, all P<0.05). Compared with enrofloxacin group, mice in minocycline group had shorter floating immobility time ((169.30±13.04) s, (224.30±22.60) s, P<0.05) and higher sugar water preference rate ((62.81±7.75) %, (47.71±8.11) %, P<0.05), the mean value of platform approach estimation after water maze correction was lower ((97.66±14.56) mm, (120.20±12.08) mm, P<0.05), and the expression level of Nissl bodies was higher ((80.17±10.55) cells /mm 2, (52.00±8.94) cells /mm 2, P<0.05), NeuN expression rate was high ((45.04±3.62) %, (28.88±4.50) %, P<0.05), Iba-1 expression was lower ((97.33±10.67) cells/mm 2, (112.50±6.54)cells/mm 2, P<0.05), the percent of M1 microglia expression was lower ((54.43±5.22) %, (73.82±6.88) %, P<0.05), and the percent of M2 microglia expression was significantly higher ((51.86±6.22) %, (36.30±5.72) %, P<0.05). The expression levels of IL-6 ((0.75±0.06), (1.21±0.07), P<0.05) and IL-1β ((0.61±0.06) (1.09±0.09), P<0.05) were lower. Conclusion:The long-term spatial memory impairment of post-stroke depression mice is aggravated, which is related to the neuron damage caused by increased activation of M1 microglia in PFC area.Inhibition of M1 microglia by minocycline can effectively improve the spatial memory ability of mice.

13.
Article in Chinese | WPRIM | ID: wpr-931895

ABSTRACT

Objective:To observe the effect of edaravone dexborneol on anxiety and depression after stroke in rats, and to explore its possible mechanism.Methods:Totally 120 healthy adult male SD rats were randomly divided into sham operation group (sham), ischemia-reperfusion group (MCAO), edaravone group (Eda) and edaravone dexborneol group (ED) with 30 in each group.The middle cerebral artery occlusion (MCAO) model was established by thread occlusion.Rats in ED group and Eda group were intraperitoneally injected with edaravone(8 mg·kg -1·d -1) and edaravone dexborneol(edaravone: 8 mg·kg -1·d -1, dexborneol: 2 mg·kg -1·d -1) respectively.And rats in the other two groups were intraperitoneally injected with the same volume of normal saline.Some rats were killed after continuous administration for 3 days to detect molecular indexes, and the remaining rats were tested for behavior after continuous administration for 14 days.The levels of neclear factor κB(NF-κB)、phosphorylated NF-κB(p-NF-κB)、tumor necrosis α(TNF-α)、interleukin 1β(IL-1β) were detected by Western blot.The mRNA levels of TNF-α, IL-1β, cluster of differentiation 86(CD86), cluster of differentiation 206(CD206), inducible nitric oxide synthase(iNOS) were detected by RT-qPCR.M1 type microglia labeled with CD68, microglia labeled with ionized calcium binding adaptor molecule 1(Iba1) and neurons labeled with microtubule-associated protein 2(MAP2) were detected by immunofluorescence staining.The cerebral infarction volume was measured by TTC staining.Depression and anxiety behavior after stroke in rats was observed by the open field test and elevated plus maze test.SPSS 17.0 software was used for statistical analysis of the data.One-way ANOVA was used for multiple group comparison, and LSD-t test was used for pairwise comparison. Results:(1) The behavioral results showed that 14 days after ischemia-reperfusion, the number of entering into the open arm, the time spent in the open arm, and the time spent in the central area of the open field in the MCAO group were lower than those in the sham group ( t=20.77, 6.02, 14.63, all P<0.05). The number of entering into the open arm, the time spent in the open arm, and the time spent in the central area of the field in the ED group ( (16.22±0.49) times, (69.11±17.08) s, (3.80±0.37) s) were higher than those in the MCAO group ( (8.14±0.60) times, (41.18±9.81) s, (0.33±0.39) s) ( t=4.69, 0.38, 2.27, all P<0.05) and Eda group ( (11.11±0.26) times, (45.26±17.16) s, (1.14±0.19) s) ( t=8.63, 2.50, 7.86, all P<0.05). (2) Western blot results showed that 3 days after ischemia-reperfusion, p-NF-κB/NF-κB, TNF-α, and IL-1β levels in the MCAO group were higher than those in the sham group ( t=15.35, 12.35, 7.23, all P<0.05). The levels of p-NF-κB/NF-κB (0.49±0.02), TNF-α (0.73±0.03), IL-1β (0.61±0.01) of ischemic penumbra cortex in ED group were significantly lower than those of the MCAO group ( (1.14±0.05), (1.13±0.07), (1.34±0.14)) ( t=14.58, 7.86, 5.65, all P<0.05) and Eda group ( (0.93±0.03), (0.89±0.02), (1.04±0.36) ) ( t=9.82, 3.07, 3.30, all P<0.05). (3) RT-qPCR results showed that the level of TNF-α mRNA (1.98±0.18), IL-1β mRNA (2.00±0.35), CD86 mRNA (1.56±0.20) and iNOS mRNA (2.01±0.12) in the peri-infarct cortex of ED group were lower than those in the MCAO group ( (5.12±0.24), ( 8.15±0.22), (6.03±0.13), (7.20±0.09) ) ( t=7.86, 16.88, 16.55, 37.25, all P<0.05) and Eda group ( (2.85±0.07), (5.43±0.26), (2.67±0.27), (3.58±0.11) ) ( t=3.71, 9.41, 4.13, 11.30, all P<0.05). The level of CD206 mRNA in the peri-infarct cortex of the ED group (3.98±0.25) was higher than that in the MCAO group (2.00±0.11) ( t=7.08, P<0.05) and Eda group (3.17±0.09) ( t=3.25, P<0.05). (4) The results of immunofluorescence staining showed that the ratio of polarized M1 microglia in the peri-infarct cortex and striatum in the ED group ((20.36±9.23)%, (18.26±5.98)%)were lower than those in the MCAO group ( (83.69±12.79)%, (61.25±33.26)%) ( t=5.23, 3.02, both P<0.05) and Eda group((42.16±13.13)%, (40.23±14.22)%)( t=3.12, 2.08, both P<0.05). In addition, the number of neurons marked with MAP2 of peri-infarct cortex in the MCAO group was lower than that in the sham group( t=8.02, P<0.05), and the number of neurons marded with MAP2 of peri-infarct cortex in the ED group ((53.07±17.90) /scope) was higher than that in the MCAO group ( (26.27±9.95) /scope) ( t=6.89, P<0.05) and Eda group ( (38.69±12.03)/scope) ( t=5.26, P<0.05). (5) The results of TTC staining showed that the cerebral infarction volume in ED group ( (10.31±1.03)%) was lower than that in the MCAO group ( (34.71±1.74)%) ( t=15.31, P<0.05) and Eda group ( (26.05±1.00)%) ( t=9.88, P<0.05). Conclusion:Edaravone dexborneol can alleviate anxiety and depression in rats with cerebral ischemia-reperfusion, which may be related to the inhibition of M1 microglial polarization, the down-regulation of NF-κB signaling pathway and the enhancement of neuronal structural stability.

14.
Article in Chinese | WPRIM | ID: wpr-930994

ABSTRACT

Objective:To study the regulatory effects of transforming growth factor beta-activated kinase 1 (TAK1) on microglia pyroptosis in hypoxic-ischemic brain damage (HIBD).Methods:Primary microglia cells were isolated from fetal mice and randomly assigned into 4 groups: the control group, 5z-7-oxozeaneol (5z-7) group, oxygen-glucose deprivation (OGD) group and OGD+5z-7 group. OGD models of microglia cells were established for the OGD groups and 5z-7 groups received a small molecule TAK1 inhibitor 5z-7. Expression of phosphorylated TAK1(P-TAK1), pyroptosis related proteins including NOD-like receptor pyrin domain containing 3 (NLRP-3), apoptosis-associated speck-like protein containing a CARD (ASC) oligomers, N terminal of Gasdermin D (GSDMD-N) and interleukin 1β (IL-1β) were examined using Western blot at 0 h, 6 h and 24 h after intervention. Lactate dehydrogenase (LDH) test and transmission electron microscope were used for pyroptosis evaluation.Results:(1) Compared with the control group, expressions of all proteins including P-TAK1, NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH level showed no significant differences in the OGD group at 0 h ( P>0.05). P-TAK1 levels in OGD group at 6 h and 24 h were lower than the control group and the levels of NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH were significantly higher ( P<0.05). Microglia pyroptosis (characterized by disruption of cell membrane, extravasation of cytoplasm and chromatin margin aggregation) was observed under electron microscope. (2) 5z-7 group and OGD+5z-7 group had lower P-TAK1 levels and higher NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH levels than the control group and OGD group at 6 h and 24 h. Conclusions:The down-regulation of TAK1 phosphorylation level may promote microglia pyroptosis in HIBD. This regulatory effects is related to the up-regulation of NLRP-3 expression and the oligomerization of ASC.

15.
Article in Chinese | WPRIM | ID: wpr-930255

ABSTRACT

Objective:To explore the mechanism of dexmedetomidine (DEX) regulating microglial (MG) polarization and neuroinflammation after traumatic brain injury (TBI) in rats.Methods:Forty-two adult male SD rats were randomly (random number) divided into the sham group, TBI group, TBI+DEX group (further divided into 1 d, 3 d and 7 d subgroups), TBI+NF-κB inhibitor (pyrrolidine dithiocarbamate, PDTC) group and TBI+DEX+PDTC group, with 6 animals in each group. The rat TBI model was established according to the modified Feeney free fall method. PDTC was intraperitoneally injected 1 h after modeling with a dose of 100 mg/kg, and DEX was intraperitoneally injected 2 h after modeling with a dose of 100 μg/kg. Modified neurological severity score (mNSS) was used to evaluate rat neurological function, ELISA was used to detect serum inflammatory factors, and rats’ damaged cortex was collected to detect the phenotype markers of MG and protein expressions of MyD88 and NF-κB p65, and immunofluorescence staining was used to observe the expression and nuclear entry of NF-κB p65 in MG in injured cortex. One-way and two-way ANOVA were used to compare the measurement data among multiple groups.Results:Compared with the sham group, the mNSS score was significantly higher in the TBI group, and DEX treatment significantly decreased the mNSS score of TBI rats ( P<0.05). ELISA and Western blot results showed that in the TBI group, the tumor necrosis factor-α (TNF-α), interleukin (IL)-1β in serum and M1 phenotype marker (TNF-α, IL-1β) in brain were increased, the expression of anti-inflammatory factor IL-10 in serum and M2 phenotype markers (arginase-1 and IL-10) in brain were decreased ( P<0.05), and DEX downregulated the expression of TNF-α, IL-1β in serum and M1 phenotype markers in brain, while upregulated the level of L-10 in serum and the M2 phenotype marker in brain ( P<0.05). In addition, the expression of MyD88 and the nuclear translocation of NF-κB p65 were inhibited in the DEX group, and this effect could be enhanced by PDTC. Conclusions:DEX modulates MG activation in TBI rats by inhibiting NF-κB nuclear translocation and reduces neuroinflammation.

16.
International Eye Science ; (12): 1079-1084, 2022.
Article in Chinese | WPRIM | ID: wpr-929483

ABSTRACT

AIM: To investigate the effect of modified Zhujing pill on retinal autophagy in mice with form deprivation myopia.METHODS: Thirty C57BL/6 mice were randomly divided into a negative control group, a myopia model group and a traditional Chinese medicine intervention group, with 10 mice in each group. Except for the negative control group, all mice in the myopia model group and the traditional Chinese medicine intervention group used translucent EP tubes to cover their right eyes to make a form deprivation myopia(FDM)model; The traditional Chinese medicine intervention group gavage Zhujing pill modified suspension 0.546g/(kg·d)(0.15mL/d), the negative control group and the myopia model group were given an equal amount of normal saline(0.15mL/d)for 4wk. At the beginning and the end of the experiment respectively, the right eye diopter of the mouse was measured with a strip retinoscope, measurement of the axial length of the right eye of mouse by A-ultrasound. At the end of the experiment, the right eyes of all mice were taken for detection, and immunofluorescence method was used to locate and detect the activity and migration of the retinal microglia marker(Iba1); Transmission electron microscope observation of autophagosome formation in retinal pigment epithelial cells; Western Blot, real-time fluorescent quantitative PCR(q-PCR)to detect the autophagy marker LC3Ⅱ and p62 protein quantitative and gene expression in retinal tissues.RESULTS: At the end of the experiment, the refractive power of the right eyes of mice showed that the myopia model group and the traditional Chinese medicine intervention group formed relative myopia, the myopia model group and the traditional Chinese medicine intervention group were significantly lower than those of the negative control group(all P&#x003C;0.01). At the end of the experiment, the axial length of the myopia model group and the Chinese medicine intervention group were significantly increased compared with the negative control group(P&#x003C;0.01). Immunofluorescence method for locating and detecting Iba1 showed that the average optical density of Iba1 in the retina of the myopia model group increased the most obviously, followed by the increase in the negative control group, and the decrease in the traditional Chinese medicine intervention group. Compared with the negative control group, the myopia model group increased significantly(P&#x003C;0.05), and the traditional Chinese medicine intervention group was significantly lower than the myopia model group(P&#x003C;0.05). It was found that Iba1 migrated to the ganglion cell layer in the myopia model group and the traditional Chinese medicine intervention group. Transmission electron microscopy showed that autophagosomes were observed in the retinal pigment epithelial cells of the myopia model group and the Chinese medicine intervention group. The results of Western Blot and q-PCR showed that the expression of LC3Ⅱ and p62 increased most obviously in the traditional Chinese medicine intervention group, followed by the myopia model group, and the negative control group was the lowest.CONCLUSION: The results of the study show that modified Zhujing pill may enhance retinal autophagy in mice with FDM by inhibiting the activation of microglia.

17.
Article in Chinese | WPRIM | ID: wpr-940832

ABSTRACT

ObjectiveTo establish a neuroinflammation-based obesity and depression comorbidity (COM) model in mice and explore the pharmacodynamics and preliminary pharmacological mechanism of tripterine on COM mice. MethodC57BL/6J mice were randomly divided into a normal group (Chow), a diet-induced obesity group (DIO), and a COM group. The mice in the COM group were fed on a high-fat diet and chronically stressed with moist litter for 12 weeks to establish the COM model. C57BL/6J mice were randomly divided into a Chow group, a COM group, and a tumor necrosis factor-α(TNF-α) knock-down group. In the TNF-α knock-down group, TNF-α shRNA adeno-associated virus was injected into the amygdala through brain stereotaxis, and the expression of TNF-α in the amygdala was down-regulated. C57BL/6J mice were randomly divided into a Chow group, a DIO group, a DIO + low-dose tripterine group (0.5 mg·kg-1), a DIO + high-dose tripterine group (1.0 mg·kg-1), a COM group, a COM + low-dose tripterine group (0.5 mg·kg-1), and a COM + high-dose tripterine group (1.0 mg·kg-1). The body weight, food intake, glucose tolerance, white/brown fat ratio, serum total cholesterol (TC), triglyceride (TG), and high-/low-density lipoprotein cholesterol (HDL-C and LDL-C) content were recorded, and obesity of mice in each group was evaluated. Forced swimming test (FST), tail suspension test (TST), and open field test were used to evaluate the degree of depression of mice in each group. Immunofluorescence staining was used to detect the protein expression levels of neuropeptide Y, tryptophan hydroxylase 2 (TPH2), and brain-derived neurotrophic factor (BDNF) in various brain nuclei of mice. Correlation analysis was used to detect the correlation of obesity and depression indexes. ResultThe comparison of the Chow group and the DIO group indicated that COM mice showed obesity and depression. To be specific, obesity was manifested as increased body weight and food intake (P<0.05, P<0.01), as well as increased NPY expression in the central amygdala, and depression was manifested as prolonged immobility time in FST and TST (P<0.01), and reduced TPH2-positive 5-hydroxytryptamine neurons in the dorsal raphe nucleus (DRN) and basolateral nucleus of the amygdala (BLA). The down-regulation of TNF-α protein in BLA of COM mice shortened the immobility time in FST and TST (P<0.05, P<0.01), increased TPH2/BDNF-positive neurons in BLA, and showed no significant changes in obesity. In DIO mice, the administration of 0.5 mg·kg-1 tripterine for 9 days significantly decreased the 60 min blood glucose in glucose tolerance (P<0.01) and food intake (P<0.05). In COM mice, 1.0 mg·kg-1 tripterine was administered for 14 days to significantly decrease 30 min blood glucose in glucose tolerance (P<0.01), and food intake (P<0.05), and immobility time in TST (P<0.01), increase TPH2-BDNF double-labeled cells in BLA and DRN, and reduce the area of TMEM119-stained cells. ConclusionThe model of obesity and depression comorbidity can be properly induced in mice under the condition of dual stress of energy environment. Tripterine can effectively interfere with obesity-depression comorbidity, and its mechanism may be related to the inhibition of central nervous system inflammation.

18.
Article in Chinese | WPRIM | ID: wpr-940344

ABSTRACT

ObjectiveTo study the inhibitory effect of Banxia Houputang (BHT) on lipopolysaccharide (LPS)-induced inflammation of microglia (BV2) cells and the neuroprotective effect on human neuroblastoma (SH-SY5Y) cells. MethodAfter the neuroinflammatory model was constructed by LPS inducing BV2 cells, model group (LPS 100 µg·L-1), administration groups (LPS+1 g·L-1 BHT, LPS+2 g·L-1 BHT, LPS+5 g·L-1 BHT, LPS+10 g·L-1 BHT), and blank group were given DEME medium at the same volume. In addition, neuronal apoptosis model was established by co-culture of LPS-induced BV2 cell inflammation medium and SH-SY5Y cells (LPS-DMEM) and was administrated according to the above grouping. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay. The content of nitric oxide (NO) and that of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were determined by Griess aasay and enzyme-linked immunosorbent assay (ELISA), respectively. The mRNA levels of TNF-α, IL-1β, interleukin-4 (IL-4), nitric oxide synthase (iNOS), and interleukin-10 (IL-10) were measured by real-time polymerase chain reaction (Real-rime PCR). Western blot was used to detect the expression levels of signal transducer and activator of transcription 3 (STAT3), Janus kinase 2 (JAK2) and nuclear factor kappa-B (NF-κB p65), protein kinase B (Akt), inhibitor of nuclear factor κB α (IκBα), B-cell lymphoma-2 (Bcl-2), and Bcl-2 associated X protein (Bax). ResultCompared with blank group, LPS increased the NO release, levels of TNF-α, IL-1β, IL-6, and iNOS and protein expression of Akt, NF-κB p65, IκBα, JAK2 and STAT3, decreased the content of IL-4 and IL-10 in BV2 cells, and induced apoptosis of co-cultured SH-SY5Y cells (P<0.01). Compared with model group, BHT reduced the content of NO, TNF-α, IL-1β, and iNOS (P<0.01) and protein expression of Akt, NF-κB p65, IκBα, JAK2 and STAT3 (P<0.01), elevated the content of IL-4 and IL-10 (P<0.01), and inhibited the apoptosis of SH-SY5Y cells induced by LPS-DMEM (P<0.01). ConclusionThis experiment reveals that BHT inhibited LPS-induced inflammation in BV2 cells by regulating Akt/NF-κB/JAK2/STAT3 signaling pathway and showed neuroprotective effects on SH-SY5Y cells.

19.
Neuroscience Bulletin ; (6): 753-768, 2022.
Article in English | WPRIM | ID: wpr-939840

ABSTRACT

A transient ischemic attack (TIA) can cause reversible and delayed impairment of cognition, but the specific mechanisms are still unclear. Annexin a1 (ANXA1) is a phospholipid-binding protein. Here, we confirmed that cognition and hippocampal synapses were impaired in TIA-treated mice, and this could be rescued by multiple mild stimulations (MMS). TIA promoted the interaction of ANXA1 and CX3CR1, increased the membrane distribution of CX3CR1 in microglia, and thus enhanced the CX3CR1 and CX3CL1 interaction. These phenomena induced by TIA could be reversed by MMS. Meanwhile, the CX3CR1 membrane distribution and CX3CR1-CX3CL1 interaction were upregulated in primary cultured microglia overexpressing ANXA1, and the spine density was significantly reduced in co-cultured microglia overexpressing ANXA1 and neurons. Moreover, ANXA1 overexpression in microglia abolished the protection of MMS after TIA. Collectively, our study provides a potential strategy for treating the delayed synaptic injury caused by TIA.


Subject(s)
Animals , Annexin A1/metabolism , CX3C Chemokine Receptor 1/metabolism , Chemokine CX3CL1 , Cognition , Dendritic Spines/metabolism , Ischemic Attack, Transient , Mice , Microglia/metabolism
20.
Article in English | WPRIM | ID: wpr-939804

ABSTRACT

OBJECTIVES@#Because intracerebral hemorrhage (ICH) has high morbidity, disability and mortality, it is significant to find new and effective treatments for ICH. This study aims to explore the effect of butyphthalide (NBP) on neuroinflammation secondary to ICH and microglia polarization.@*METHODS@#A total of 48 healthy male SD rats were randomly divided into 6 groups: a sham 24 h group, a sham 72 h group, an ICH 24 h group, an ICH 72 h group, an ICH+NBP 24 h group, and an ICH+NBP 72 h group (8 rats per group). After operation, the neurological deficiencies were assessed based on improved Garcia scores and corner test. The expressions of Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), aquaporin-4 (AQP4), zonula occludens-1 (ZO-1), occludin, CD68, CD86, and CD206 were observed by Western blotting. Inflammatory cytokines were detected by ELISA. The immunofluorescence was to detect the polarization of microglia.@*RESULTS@#1) Compared with the sham groups, the expression of TLR4 (24 h: P<0.05; 72 h: P<0.01), NF-κB (both P<0.01) and Nrf2 (both P<0.01) in the perihematoma of the ICH group was increased, leading to microglia activation (P<0.01). The expressions of IL-6 (24 h: P<0.05; 72 h: P<0.01) and TNF-α (both P<0.01), the pro-inflammatory cytokines were up-regulated, and the expression of anti-inflammatory cytokine IL-4 was down-regulated (both P<0.01). Besides, the expression of AQP4 was enhanced (both P<0.01). The protein level of tightly connected proteins (including ZO-1, occludin) was decreased (all P<0.01). The neurological function of the rats in the ICH group was impaired in the 2 time points (both P<0.01). 2) Compared with the sham group at 24 h and 72 h after the intervention of NBP, the expressions of TLR4 (both P<0.05) and NF-κB (both P<0.01) were significantly declined, and the expression of Nrf2 was further enhanced (both P<0.05) in the perihematoma of the ICH+NBP group. Furthermore, the expression of M1 microglia marker was inhibited (P<0.05), and the polarization of microglia to the M2 phenotype was promoted (P<0.01). 3) In terms of inflammation after ICH, the IL-4 expression in the ICH+NBP group was increased compared with the ICH group (24 h: P<0.05; 72 h: P<0.01); the expression of IL-6 was decreased significantly in the ICH+NBP 72 h group (P<0.01); the level of AQP4 was declined significantly in the ICH+NBP 24 h group (P<0.05), there was a downward trend in the 72-hour intervention group but without significant statistical difference. 4) Compared with the ICH group, the ZO-1 protein levels were increased (24 h: P<0.05; 72 h: P<0.01), and the symptoms of nerve defect were improved eventually (both P<0.05) in the ICH+NBP groups.@*CONCLUSIONS@#After ICH, the TLR4/NF-κB pathway is activated. The M1 microglia is up-regulated along with the release of detrimental cytokines, while the anti-inflammatory cytokines are down-regulated. The expression of AQP4 is increased, the tight junction proteins from the blood-brain barrier (BBB) is damaged, and the neurological function of rats is impaired. On the contrary, NBP may regulate microglia polarization to M2 phenotype and play a role in the neuroprotective effect mediated via inhibiting TLR4/NF-κB and enhancing Nrf2 pathways, which relieves the neuroinflammation, inhibits the expression of AQP4, repairs BBB, and improves neurological functional defects.


Subject(s)
Animals , Anti-Inflammatory Agents/therapeutic use , Cerebral Hemorrhage , Cytokines/metabolism , Interleukin-4/therapeutic use , Interleukin-6/metabolism , Male , Microglia/metabolism , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , Occludin/pharmacology , Rats , Rats, Sprague-Dawley , Signal Transduction , Toll-Like Receptor 4/genetics
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