Pub Date : 2022-01-01Epub Date: 2021-08-24DOI: 10.1159/000518215
Meijing Wang, Hongyan Liu, Lufeng Xu, Mengmeng Li, Ming Zhao
Introduction: Isoflurane inhalation leads to apoptotic neurodegeneration and further results in learning and cognitive dysfunction. Notoginsenoside R1 (NGR1), a major ingredient from Radix notoginseng, has been reported to exert neuroprotective effect during brain or neuron injury. This study aimed to investigate the effect of NGR1 on neurological impairment.
Methods: Sixty-four male Sprague Dawley rat pups (15-20 g) of postnatal day 7 were recruited. Spatial learning and memory were assessed by the Morris water maze test, and the neurological severity score was determined. Real-time quantitative PCR was used to detect the expression levels of microRNA (miR)-29a. Enzyme-linked immunosorbent assay was applied to estimate the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the hippocampal tissues.
Results: NGR1 attenuated neurological impairment induced by isoflurane, shown by the decrease in neurological function score and escape latency and the increase in staying time in the original quadrant in rats. NGR1 reversed the downregulation of miR-29a expression induced by isoflurane treatment. After the treatment of NGR1, the elevated levels of IL-6, TNF-α, and IL-1β induced by isoflurane were all decreased significantly in the hippocampal tissues of rats. Additionally, the repressive action of NGR1 in neurological impairment and neuroinflammation was eliminated by downregulating miR-29a in rats.
Conclusion: NGR1 protects against isoflurane-induced neurological impairment. The protective effect of NGR1 might be achieved by promoting the expression of miR-29a and preventing inflammatory response.
{"title":"The Protective Effect of Notoginsenoside R1 on Isoflurane-Induced Neurological Impairment in the Rats via Regulating miR-29a Expression and Neuroinflammation.","authors":"Meijing Wang, Hongyan Liu, Lufeng Xu, Mengmeng Li, Ming Zhao","doi":"10.1159/000518215","DOIUrl":"https://doi.org/10.1159/000518215","url":null,"abstract":"<p><strong>Introduction: </strong>Isoflurane inhalation leads to apoptotic neurodegeneration and further results in learning and cognitive dysfunction. Notoginsenoside R1 (NGR1), a major ingredient from Radix notoginseng, has been reported to exert neuroprotective effect during brain or neuron injury. This study aimed to investigate the effect of NGR1 on neurological impairment.</p><p><strong>Methods: </strong>Sixty-four male Sprague Dawley rat pups (15-20 g) of postnatal day 7 were recruited. Spatial learning and memory were assessed by the Morris water maze test, and the neurological severity score was determined. Real-time quantitative PCR was used to detect the expression levels of microRNA (miR)-29a. Enzyme-linked immunosorbent assay was applied to estimate the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the hippocampal tissues.</p><p><strong>Results: </strong>NGR1 attenuated neurological impairment induced by isoflurane, shown by the decrease in neurological function score and escape latency and the increase in staying time in the original quadrant in rats. NGR1 reversed the downregulation of miR-29a expression induced by isoflurane treatment. After the treatment of NGR1, the elevated levels of IL-6, TNF-α, and IL-1β induced by isoflurane were all decreased significantly in the hippocampal tissues of rats. Additionally, the repressive action of NGR1 in neurological impairment and neuroinflammation was eliminated by downregulating miR-29a in rats.</p><p><strong>Conclusion: </strong>NGR1 protects against isoflurane-induced neurological impairment. The protective effect of NGR1 might be achieved by promoting the expression of miR-29a and preventing inflammatory response.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":"29 1","pages":"70-76"},"PeriodicalIF":2.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39410771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Neuropathic pain (NP) is one of the most severe chronic pain types. In recent years, more and more studies have shown that long noncoding RNA (LncRNA) plays a key role in a variety of human diseases, including NP. However, the role of LncRNA prostate cancer-associated transcript 19 (PCAT19) in NP and its specific mechanism remain unclear.
Methods: A chronic constrictive injury (CCI) rat model was established. Rat paw withdrawal threshold and paw withdrawal latency were used to evaluate the neuronal pain behavior of rats in this model. mRNA expression of PCAT19, neuroinflammatory factor, microRNA (miR)-182-5p, and Jumonji domain containing 1A (JMJD1A) were detected by quantitative real-time PCR. ELISA analysis was used to detect inflammatory factor protein expression. Dual-luciferase reporter assay was used to evaluate the targeting relationship between genes.
Results: PCAT19 was continuously upregulated in CCI rats. miR-182-5p was the target of PCAT19, and miR-182-5p was increased after PCAT19 knockdown. NP behaviors such as mechanical ectopic pain and thermal hyperalgesia as well as neuroinflammation can be reduced by knocking down PCAT19. However, the injection of miR-182-5p antagomir significantly reversed the level of the NP behaviors and neuroinflammation caused by PCAT19 knockdown. Besides, dual-luciferase reporter assay showed that JMJD1A was the target gene of miR-182-5p. The level of JMJD1A in CCI rats increased with time. After PCAT19 knockdown, JMJD1A was significantly decreased, but inhibition of miR-182-5p can reverse its levels.
Conclusion: This study shows that PCAT19 plays a role in NP by targeting the miR-182-5p/JMJD1A axis, and PCAT19 can be used as a new therapeutic target for NP.
{"title":"LncRNA PCAT19 Regulates Neuropathic Pain via Regulation of miR-182-5p/JMJD1A in a Rat Model of Chronic Constriction Injury.","authors":"Miao Huo, Xingxing Zheng, Ning Bai, Ruifen Xu, Guang Yang, Ziyu Zhao","doi":"10.1159/000518847","DOIUrl":"https://doi.org/10.1159/000518847","url":null,"abstract":"<p><strong>Introduction: </strong>Neuropathic pain (NP) is one of the most severe chronic pain types. In recent years, more and more studies have shown that long noncoding RNA (LncRNA) plays a key role in a variety of human diseases, including NP. However, the role of LncRNA prostate cancer-associated transcript 19 (PCAT19) in NP and its specific mechanism remain unclear.</p><p><strong>Methods: </strong>A chronic constrictive injury (CCI) rat model was established. Rat paw withdrawal threshold and paw withdrawal latency were used to evaluate the neuronal pain behavior of rats in this model. mRNA expression of PCAT19, neuroinflammatory factor, microRNA (miR)-182-5p, and Jumonji domain containing 1A (JMJD1A) were detected by quantitative real-time PCR. ELISA analysis was used to detect inflammatory factor protein expression. Dual-luciferase reporter assay was used to evaluate the targeting relationship between genes.</p><p><strong>Results: </strong>PCAT19 was continuously upregulated in CCI rats. miR-182-5p was the target of PCAT19, and miR-182-5p was increased after PCAT19 knockdown. NP behaviors such as mechanical ectopic pain and thermal hyperalgesia as well as neuroinflammation can be reduced by knocking down PCAT19. However, the injection of miR-182-5p antagomir significantly reversed the level of the NP behaviors and neuroinflammation caused by PCAT19 knockdown. Besides, dual-luciferase reporter assay showed that JMJD1A was the target gene of miR-182-5p. The level of JMJD1A in CCI rats increased with time. After PCAT19 knockdown, JMJD1A was significantly decreased, but inhibition of miR-182-5p can reverse its levels.</p><p><strong>Conclusion: </strong>This study shows that PCAT19 plays a role in NP by targeting the miR-182-5p/JMJD1A axis, and PCAT19 can be used as a new therapeutic target for NP.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":"29 2","pages":"161-170"},"PeriodicalIF":2.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39413585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2021-12-02DOI: 10.1159/000519124
Yanhu Ge, Duomao Lin, Boqun Cui, Liang Zhang, Shurong Li, Zhaoqi Wang, Jun Ma
Introduction: Isoflurane (ISO) may cause neuronal apoptosis and synaptic disorder during development, and damage long-term learning and memory function. This observation aimed to study the function of H19 in vitro and in vivo tests and the further mechanism was identified.
Methods: ISO cell models and rat models were established and reactive oxygen species (ROS) identified. The viability and apoptosis of HT22 cells were detected by the MTT and flow cytometer. Morris water maze test was conducted to analyze the neurotoxicity of ISO on spatial learning and memory ability. Quantitative PCR was the method to verify the expression of H19. The concentration of inflammatory indicators was identified by enzyme-linked immunosorbent assay.
Results: 1.5% and 2% ISO led to the neurotoxicity of HT22 cells and increased expression of H19. Silenced H19 meliorated these adverse impacts of ISO. Interference of H19 exerted neuroprotective roles by repressing modified neurological severity score, inhibiting escape latency, elevating distance and time of target area, and controlling ROS and inflammation. MiR-17-5p might be a promising competing endogenous RNA of H19. The expression of miR-17-5p was reduced in the ISO group and reversed by the absence of H19.
Conclusion: Our results of in vitro and in vivo assay indicated that the absence of HT22 is a neuroprotective regulator of cognition and inflammation by accumulating miR-17-5p.
{"title":"Effects of Long Noncoding RNA H19 on Isoflurane-Induced Cognitive Dysregulation by Promoting Neuroinflammation.","authors":"Yanhu Ge, Duomao Lin, Boqun Cui, Liang Zhang, Shurong Li, Zhaoqi Wang, Jun Ma","doi":"10.1159/000519124","DOIUrl":"https://doi.org/10.1159/000519124","url":null,"abstract":"<p><strong>Introduction: </strong>Isoflurane (ISO) may cause neuronal apoptosis and synaptic disorder during development, and damage long-term learning and memory function. This observation aimed to study the function of H19 in vitro and in vivo tests and the further mechanism was identified.</p><p><strong>Methods: </strong>ISO cell models and rat models were established and reactive oxygen species (ROS) identified. The viability and apoptosis of HT22 cells were detected by the MTT and flow cytometer. Morris water maze test was conducted to analyze the neurotoxicity of ISO on spatial learning and memory ability. Quantitative PCR was the method to verify the expression of H19. The concentration of inflammatory indicators was identified by enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>1.5% and 2% ISO led to the neurotoxicity of HT22 cells and increased expression of H19. Silenced H19 meliorated these adverse impacts of ISO. Interference of H19 exerted neuroprotective roles by repressing modified neurological severity score, inhibiting escape latency, elevating distance and time of target area, and controlling ROS and inflammation. MiR-17-5p might be a promising competing endogenous RNA of H19. The expression of miR-17-5p was reduced in the ISO group and reversed by the absence of H19.</p><p><strong>Conclusion: </strong>Our results of in vitro and in vivo assay indicated that the absence of HT22 is a neuroprotective regulator of cognition and inflammation by accumulating miR-17-5p.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":"29 2","pages":"117-127"},"PeriodicalIF":2.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39938635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2021-06-16DOI: 10.1159/000516559
Fatemeh Lotfi, Marjan Mansourian, Omid Mirmoayyeb, Soroush Najdaghi, Vahid Shaygannejad, Nafiseh Esmaeil
The association between air pollution and multiple sclerosis (MS) is not entirely clear. This meta-analysis was aimed at determining the correlation between particulate matter (PM)2.5, PM10, and MS incidence/relapse. The literature search was performed in EMBASE, Web of Science, PubMed, and the gray literature. Sixteen articles were retrieved, and ten articles were included and evaluated. Three measures of association were used for the meta-analysis: odds ratio (cross-sectional and case-control studies), incidence rate ratio, or hazard ratio (cohort studies). Meta-analysis of those 3 studies on PM2.5 indicated that exposure to PM2.5 was associated with MS relapse and incidence ([95% confidence interval; CI] 1.178 [1.102, 1.279]), p > 0.05. Also, assessment of risk ratio for all studies showed a correlation between PMs (PM10 and PM2.5) and MS incidence and relapse ([95% CI] 1.28, [1.13-1.43]) p < 0.05. Collectively, we found that PM exposure (PM10 and PM2.5) in MS patients associates with the occurrence and relapse of disease.
空气污染与多发性硬化症(MS)之间的关系尚不完全清楚。该荟萃分析旨在确定颗粒物(PM)2.5、PM10与MS发病率/复发之间的相关性。在EMBASE、Web of Science、PubMed和灰色文献中进行文献检索。16篇文章被检索,10篇文章被纳入并评价。meta分析使用了三种关联指标:优势比(横断面和病例对照研究)、发病率比或风险比(队列研究)。对这3项PM2.5研究的荟萃分析表明,暴露于PM2.5与MS复发和发病率相关(95%可信区间;CI] 1.178 [1.102, 1.279]), p > 0.05。此外,所有研究的风险比评估显示pm (PM10和PM2.5)与MS发病率和复发之间存在相关性([95% CI] 1.28, [1.13-1.43]) p < 0.05。总的来说,我们发现MS患者的PM暴露(PM10和PM2.5)与疾病的发生和复发有关。
{"title":"Association of Exposure to Particulate Matters and Multiple Sclerosis: A Systematic Review and Meta-Analysis.","authors":"Fatemeh Lotfi, Marjan Mansourian, Omid Mirmoayyeb, Soroush Najdaghi, Vahid Shaygannejad, Nafiseh Esmaeil","doi":"10.1159/000516559","DOIUrl":"https://doi.org/10.1159/000516559","url":null,"abstract":"<p><p>The association between air pollution and multiple sclerosis (MS) is not entirely clear. This meta-analysis was aimed at determining the correlation between particulate matter (PM)2.5, PM10, and MS incidence/relapse. The literature search was performed in EMBASE, Web of Science, PubMed, and the gray literature. Sixteen articles were retrieved, and ten articles were included and evaluated. Three measures of association were used for the meta-analysis: odds ratio (cross-sectional and case-control studies), incidence rate ratio, or hazard ratio (cohort studies). Meta-analysis of those 3 studies on PM2.5 indicated that exposure to PM2.5 was associated with MS relapse and incidence ([95% confidence interval; CI] 1.178 [1.102, 1.279]), p > 0.05. Also, assessment of risk ratio for all studies showed a correlation between PMs (PM10 and PM2.5) and MS incidence and relapse ([95% CI] 1.28, [1.13-1.43]) p < 0.05. Collectively, we found that PM exposure (PM10 and PM2.5) in MS patients associates with the occurrence and relapse of disease.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":"29 1","pages":"21-27"},"PeriodicalIF":2.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000516559","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39237450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2021-09-08DOI: 10.1159/000517901
Amir Mohammadi, Abasalt Hosseinzadeh Colagar, Ayeh Khorshidian, Seyed Mohammad Amini
Progressive abnormality and loss of axons and neurons in the central nervous system (CNS) cause neurodegenerative diseases (NDs). Protein misfolding and its collection are the most important pathological features of NDs. Astrocytes are the most plentiful cells in the mammalian CNS (about 20-40% of the human brain) and have several central functions in the maintenance of the health and correct function of the CNS. Astrocytes have an essential role in the preservation of brain homeostasis, and it is not surprising that these multifunctional cells have been implicated in the onset and progression of several NDs. Thus, they become an exciting target for the study of NDs. Over almost 15 years, it was revealed that curcumin has several therapeutic effects in a wide variety of diseases' treatment. Curcumin is a valuable ingredient present in turmeric spice and has several essential roles, including those which are anticarcinogenic, hepatoprotective, thrombosuppressive, cardioprotective, anti-arthritic, anti-inflammatory, antioxidant, chemopreventive, chemotherapeutic, and anti-infectious. Furthermore, curcumin can suppress inflammation; promote angiogenesis; and treat diabetes, pulmonary problems, and neurological dysfunction. Here, we review the effects of curcumin on astrocytes in NDs, with a focus on Alzheimer's disease, Parkinson's disease, multiple scleroses, Huntington's disease, and amyotrophic lateral sclerosis.
{"title":"The Functional Roles of Curcumin on Astrocytes in Neurodegenerative Diseases.","authors":"Amir Mohammadi, Abasalt Hosseinzadeh Colagar, Ayeh Khorshidian, Seyed Mohammad Amini","doi":"10.1159/000517901","DOIUrl":"https://doi.org/10.1159/000517901","url":null,"abstract":"<p><p>Progressive abnormality and loss of axons and neurons in the central nervous system (CNS) cause neurodegenerative diseases (NDs). Protein misfolding and its collection are the most important pathological features of NDs. Astrocytes are the most plentiful cells in the mammalian CNS (about 20-40% of the human brain) and have several central functions in the maintenance of the health and correct function of the CNS. Astrocytes have an essential role in the preservation of brain homeostasis, and it is not surprising that these multifunctional cells have been implicated in the onset and progression of several NDs. Thus, they become an exciting target for the study of NDs. Over almost 15 years, it was revealed that curcumin has several therapeutic effects in a wide variety of diseases' treatment. Curcumin is a valuable ingredient present in turmeric spice and has several essential roles, including those which are anticarcinogenic, hepatoprotective, thrombosuppressive, cardioprotective, anti-arthritic, anti-inflammatory, antioxidant, chemopreventive, chemotherapeutic, and anti-infectious. Furthermore, curcumin can suppress inflammation; promote angiogenesis; and treat diabetes, pulmonary problems, and neurological dysfunction. Here, we review the effects of curcumin on astrocytes in NDs, with a focus on Alzheimer's disease, Parkinson's disease, multiple scleroses, Huntington's disease, and amyotrophic lateral sclerosis.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":"29 1","pages":"4-14"},"PeriodicalIF":2.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39395666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: This study aimed to observe the changes of resting energy metabolism in patients with severe neurological diseases, and to explore the effects of tracheostomy status, stroke severity, and complications on resting energy expenditure (REE) and respiratory quotient (RQ).
Methods: A retrospective study was conducted in 105 patients with neurological rehabilitation who were hospitalized in the Rehabilitation Department of the Affiliated Jiangning Hospital of Nanjing Medical University from August 2018 to October 2021. REE was measured by Italian Cosmed k4b2 indirectly, and white blood cell count and C-reactive protein (CRP) were collected.
Results: Among the 105 patients, there were 18 cases of mild stroke, 45 cases of moderate stroke, and 42 cases of severe stroke. The difference between predicted REE and actual REE among different degrees of stroke patients was statistically significant (p < 0.05); there was no significant difference in RQ values among different degrees of stroke patients (p > 0.05). Hemoglobin, albumin, and body mass index were significantly and positively correlated with predicted REE and actual REE, while CRP was significantly negatively correlated with predicted REE and actual REE. There was no significant difference in predicted REE, actual REE, and RQ between renal insufficiency, type 2 diabetes mellitus, and chronic obstructive pulmonary disease (p > 0.05). The CRP level could affect the REE of stroke patients.
Conclusion: Metabolic vehicle assay has a certain clinical value in accurately evaluating the metabolic needs and feeding level of patients.
{"title":"Analysis of Resting Energy Consumption and Its Influencing Factors in Stroke Patients with Severe Neurological Diseases: A Retrospective Clinical Study.","authors":"Hui Feng, Huaping Pan, Wei Yao, Chengyao Mei","doi":"10.1159/000524719","DOIUrl":"https://doi.org/10.1159/000524719","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to observe the changes of resting energy metabolism in patients with severe neurological diseases, and to explore the effects of tracheostomy status, stroke severity, and complications on resting energy expenditure (REE) and respiratory quotient (RQ).</p><p><strong>Methods: </strong>A retrospective study was conducted in 105 patients with neurological rehabilitation who were hospitalized in the Rehabilitation Department of the Affiliated Jiangning Hospital of Nanjing Medical University from August 2018 to October 2021. REE was measured by Italian Cosmed k4b2 indirectly, and white blood cell count and C-reactive protein (CRP) were collected.</p><p><strong>Results: </strong>Among the 105 patients, there were 18 cases of mild stroke, 45 cases of moderate stroke, and 42 cases of severe stroke. The difference between predicted REE and actual REE among different degrees of stroke patients was statistically significant (p < 0.05); there was no significant difference in RQ values among different degrees of stroke patients (p > 0.05). Hemoglobin, albumin, and body mass index were significantly and positively correlated with predicted REE and actual REE, while CRP was significantly negatively correlated with predicted REE and actual REE. There was no significant difference in predicted REE, actual REE, and RQ between renal insufficiency, type 2 diabetes mellitus, and chronic obstructive pulmonary disease (p > 0.05). The CRP level could affect the REE of stroke patients.</p><p><strong>Conclusion: </strong>Metabolic vehicle assay has a certain clinical value in accurately evaluating the metabolic needs and feeding level of patients.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":"29 4","pages":"460-467"},"PeriodicalIF":2.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10394868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lin Zhu, Ce Dong, Xiongfei Yue, Pengzhen Ge, Guozhen Zheng, Zhanying Ye, Baogen Pan
Background: Neuroinflammation subsequent to traumatic brain injury (TBI) is important for the recovery of patients and is associated with neurodegenerative changes post-TBI. The tripartite motif containing 44 (TRIM44) protein is an E3 ligase involved in the regulation of immune function with no previously known link to TBI. This study explores the connection between TRIM44 and TBI.
Methods: After induction of TBI in rats by control cortex injury, TRIM44 expressions were determined with quantitative real-time reverse transcription polymerase chain reaction and Western blot, and Toll-like receptor 4 (TLR4)-NF-κB signaling was examined by the expression of TLR4, p65 phosphorylation, and the specific NF-κB transcription activity. The effects of TRIM44 knockdown on inflammation, neurological function, and TLR4-NF-κB signaling in TBI rats were revealed by the detection of proinflammatory cytokines and TLR4-NF-κB signaling molecules, modified neurological severity score, brain water content, and Evans blue permeability.
Results: We found that TRIM44 expression was significantly increased following TBI induction along with TLR4-NF-κB activation. Silencing of TRIM44 suppressed proinflammatory cytokine production, improved neurological outcomes, alleviated brain edema, and inhibited TLR4-NF-κB signaling in TBI rats.
Conclusion: Our findings suggest that suppressing TRIM44 or modulation of relevant pathways may be a therapeutic strategy for TBI.
{"title":"Silencing of TRIM44 Inhibits Inflammation and Alleviates Traumatic Brain Injury in Rats by Downregulating TLR4-NF-κB Signaling.","authors":"Lin Zhu, Ce Dong, Xiongfei Yue, Pengzhen Ge, Guozhen Zheng, Zhanying Ye, Baogen Pan","doi":"10.1159/000524536","DOIUrl":"https://doi.org/10.1159/000524536","url":null,"abstract":"<p><strong>Background: </strong>Neuroinflammation subsequent to traumatic brain injury (TBI) is important for the recovery of patients and is associated with neurodegenerative changes post-TBI. The tripartite motif containing 44 (TRIM44) protein is an E3 ligase involved in the regulation of immune function with no previously known link to TBI. This study explores the connection between TRIM44 and TBI.</p><p><strong>Methods: </strong>After induction of TBI in rats by control cortex injury, TRIM44 expressions were determined with quantitative real-time reverse transcription polymerase chain reaction and Western blot, and Toll-like receptor 4 (TLR4)-NF-κB signaling was examined by the expression of TLR4, p65 phosphorylation, and the specific NF-κB transcription activity. The effects of TRIM44 knockdown on inflammation, neurological function, and TLR4-NF-κB signaling in TBI rats were revealed by the detection of proinflammatory cytokines and TLR4-NF-κB signaling molecules, modified neurological severity score, brain water content, and Evans blue permeability.</p><p><strong>Results: </strong>We found that TRIM44 expression was significantly increased following TBI induction along with TLR4-NF-κB activation. Silencing of TRIM44 suppressed proinflammatory cytokine production, improved neurological outcomes, alleviated brain edema, and inhibited TLR4-NF-κB signaling in TBI rats.</p><p><strong>Conclusion: </strong>Our findings suggest that suppressing TRIM44 or modulation of relevant pathways may be a therapeutic strategy for TBI.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":"29 4","pages":"439-449"},"PeriodicalIF":2.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10476631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yong-Ping Zhang, Yu-Yu Li, Cai Zhang, Ya-Jun Li, Bai-Ping Liu, Yan Zhang, Ju-Da Lin, Cai Song
Background: Activated microglia can trigger pro-inflammatory cytokine releases and neuroinflammation, which may inhibit astrocytes to produce neurotrophins and anti-inflammatory factors. Both eventually lead to neuron apoptosis or death. Furthermore, effective antidepressant or anti-dementia treatments can reduce pro-inflammatory cytokines, while enhance interleukin (IL)-10 production. However, the underline mechanism by which IL-10 modulates glial cell function, hence improves cognitive impairment or depression-like behavior is unknown. This study evaluated whether and how IL-10 attenuated chronic IL-1β administration-induced behavioral changes and the possible involved mechanisms.
Methods: Rats received intracerebroventricular injection of IL-1β and/or IL-10 for 14 days. Then animal memory and depression-like behavior, pro-inflammatory cytokines, glial activities, expression of brain-derived neurotrophic factor (BDNF), Trk B, p75, and apoptosis-related genes were studied.
Results: Compared to controls, significantly increased latent time and swimming distance in the Morris-water-maze, decreased sucrose consumption, and decreased locomotor and center zone entries in the open-field were found in rats administrated with IL-1β. These changes were associated with the reduction of GFAP expression, and concentrations of BDNF and anti-inflammatory cytokine IL-10, but the increase in the expressions of CD11b, TrkB, p75, and Caspase-3, the ratio of Bax/Bcl-2, and the concentrations of IL-1β, tumor necrosis factor-α, and IL-6. IL-10 treatment markedly attenuated IL-1β-induced above changes, except for the expressions of neurotrophin receptors.
Conclusion: IL-10-improved behavioral changes may be through suppressing microglia activity and inflammation, while restoring astrocyte function and BDNF expression.
{"title":"Interleukin-10 Attenuates Behavioral, Immune and Neurotrophin Changes Induced by Chronic Central Administration of Interleukin-1β in Rats.","authors":"Yong-Ping Zhang, Yu-Yu Li, Cai Zhang, Ya-Jun Li, Bai-Ping Liu, Yan Zhang, Ju-Da Lin, Cai Song","doi":"10.1159/000521710","DOIUrl":"https://doi.org/10.1159/000521710","url":null,"abstract":"<p><strong>Background: </strong>Activated microglia can trigger pro-inflammatory cytokine releases and neuroinflammation, which may inhibit astrocytes to produce neurotrophins and anti-inflammatory factors. Both eventually lead to neuron apoptosis or death. Furthermore, effective antidepressant or anti-dementia treatments can reduce pro-inflammatory cytokines, while enhance interleukin (IL)-10 production. However, the underline mechanism by which IL-10 modulates glial cell function, hence improves cognitive impairment or depression-like behavior is unknown. This study evaluated whether and how IL-10 attenuated chronic IL-1β administration-induced behavioral changes and the possible involved mechanisms.</p><p><strong>Methods: </strong>Rats received intracerebroventricular injection of IL-1β and/or IL-10 for 14 days. Then animal memory and depression-like behavior, pro-inflammatory cytokines, glial activities, expression of brain-derived neurotrophic factor (BDNF), Trk B, p75, and apoptosis-related genes were studied.</p><p><strong>Results: </strong>Compared to controls, significantly increased latent time and swimming distance in the Morris-water-maze, decreased sucrose consumption, and decreased locomotor and center zone entries in the open-field were found in rats administrated with IL-1β. These changes were associated with the reduction of GFAP expression, and concentrations of BDNF and anti-inflammatory cytokine IL-10, but the increase in the expressions of CD11b, TrkB, p75, and Caspase-3, the ratio of Bax/Bcl-2, and the concentrations of IL-1β, tumor necrosis factor-α, and IL-6. IL-10 treatment markedly attenuated IL-1β-induced above changes, except for the expressions of neurotrophin receptors.</p><p><strong>Conclusion: </strong>IL-10-improved behavioral changes may be through suppressing microglia activity and inflammation, while restoring astrocyte function and BDNF expression.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":"29 4","pages":"380-390"},"PeriodicalIF":2.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10481585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2022-01-03DOI: 10.1159/000521574
Rainer H Straub
By studying the history of a scientific journal, we can learn more about the scientific culture of a research field and we can start to understand how it changed and what it is now. Samuel M. McCann† and James M. Lipton† (served: 1994–2001), George P. Chrousos (2002–2006), and Wilson Savino (2007–2021) were the distinguished Editors-in-Chief of Neuroimmunomodulation, giants of the science of neuro-endocrine-immune interrelations. The late Sam McCann wrote in the first Neuroimmunomodulation Editorial in Volume 1, Issue 1, 1994 [1]:
{"title":"New Editor-in-Chief's Note: The Past and the Future.","authors":"Rainer H Straub","doi":"10.1159/000521574","DOIUrl":"https://doi.org/10.1159/000521574","url":null,"abstract":"By studying the history of a scientific journal, we can learn more about the scientific culture of a research field and we can start to understand how it changed and what it is now. Samuel M. McCann† and James M. Lipton† (served: 1994–2001), George P. Chrousos (2002–2006), and Wilson Savino (2007–2021) were the distinguished Editors-in-Chief of Neuroimmunomodulation, giants of the science of neuro-endocrine-immune interrelations. The late Sam McCann wrote in the first Neuroimmunomodulation Editorial in Volume 1, Issue 1, 1994 [1]:","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":"29 1","pages":"1-3"},"PeriodicalIF":2.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39642810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yiqin Lin, Yingle Chen, Jingyang Zeng, Shunyuan Li
Background: Inflammatory pain mediated by nuclear factor kappa-B (NF-κB) signal pathway has become an increasingly important clinical issue in the last decade. As a potent antioxidant, Nodakenetin has been shown to have a prominent inhibitory effect on inflammation. However, the therapeutic effects and underlying pharmacological mechanisms of Nodakenetin for inflammatory pain remain unclear.
Methods: Intraplanar injection of complete Freund's adjuvant (CFA) was used to establish a model of chronic inflammation pain in C57BL/6 mice. The chronic neuropathic pain model was conducted by the sciatic nerve ligation surgery. QRT-PCR was performed to estimate the RNA levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Western blot was used to demonstrated the protein levels of phospho-IkappaBα (IκBα), p50, and p65 in HEK293T cells.
Results: The bioactive components of the traditional Chinese medicine Notopterygium forbesii boiss mainly include Nodakenetin, isoimperatorin, and pregnenolone. Nodakenetin significantly alleviated CFA-induced inflammatory pain but showed no significant therapeutic effect on surgically induced neuralgia in a mouse model. In contrast, isoimperatorin and pregnenolone did not relieve CFA-induced inflammatory pain. Mechanistically, Nodakenetin inhibited IL-1β-induced activation of the NF-κB pathway and phosphorylation of IκBα in HEK293T cells. Furthermore, Nodakenetin treatment suppressed the expression of IL-6, TNF-α, and IL-1β in mouse bone marrow-derived macrophages.
Conclusion: Nodakenetin alleviates inflammatory pain induced by CFA injection in vivo and modulates NF-κB signal pathway in vitro.
{"title":"Nodakenetin Alleviates Inflammatory Pain Hypersensitivity by Suppressing NF-κB Signal Pathway.","authors":"Yiqin Lin, Yingle Chen, Jingyang Zeng, Shunyuan Li","doi":"10.1159/000525690","DOIUrl":"https://doi.org/10.1159/000525690","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory pain mediated by nuclear factor kappa-B (NF-κB) signal pathway has become an increasingly important clinical issue in the last decade. As a potent antioxidant, Nodakenetin has been shown to have a prominent inhibitory effect on inflammation. However, the therapeutic effects and underlying pharmacological mechanisms of Nodakenetin for inflammatory pain remain unclear.</p><p><strong>Methods: </strong>Intraplanar injection of complete Freund's adjuvant (CFA) was used to establish a model of chronic inflammation pain in C57BL/6 mice. The chronic neuropathic pain model was conducted by the sciatic nerve ligation surgery. QRT-PCR was performed to estimate the RNA levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Western blot was used to demonstrated the protein levels of phospho-IkappaBα (IκBα), p50, and p65 in HEK293T cells.</p><p><strong>Results: </strong>The bioactive components of the traditional Chinese medicine Notopterygium forbesii boiss mainly include Nodakenetin, isoimperatorin, and pregnenolone. Nodakenetin significantly alleviated CFA-induced inflammatory pain but showed no significant therapeutic effect on surgically induced neuralgia in a mouse model. In contrast, isoimperatorin and pregnenolone did not relieve CFA-induced inflammatory pain. Mechanistically, Nodakenetin inhibited IL-1β-induced activation of the NF-κB pathway and phosphorylation of IκBα in HEK293T cells. Furthermore, Nodakenetin treatment suppressed the expression of IL-6, TNF-α, and IL-1β in mouse bone marrow-derived macrophages.</p><p><strong>Conclusion: </strong>Nodakenetin alleviates inflammatory pain induced by CFA injection in vivo and modulates NF-κB signal pathway in vitro.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":"29 4","pages":"486-492"},"PeriodicalIF":2.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10762175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}