Translational Neuroscience最新文献

{"title":"Effects of edaravone dexborneol on neurological function and serum inflammatory factor levels in patients with acute anterior circulation large vessel occlusion stroke.","authors":"Xiaohong Hu,&nbsp;Zhenhong Qian,&nbsp;Jianhui Chen,&nbsp;Mingsheng Chen,&nbsp;Wenying Zhong,&nbsp;Chaoxiong Shen,&nbsp;Zhizhou Hu,&nbsp;Rongtong Li","doi":"10.1515/tnsci-2022-0312","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0312","url":null,"abstract":"<p><p>The goal of this study is to evaluate and analyze the effects of edaravone (EDV) dexborneol on neurological function and serum inflammatory factor levels among patients with acute anterior circulation big artery blockage stroke. A total of 142 patients with acute anterior circulation large vessel occlusion (LVO) were randomly allocated to the study group (69 patients) or the control group (73 patients). In the study group, patients were treated with 37.5 mg EDV dexborneol twice a day for 10-14 days, based on the control group. The primary efficacy outcome was the National Institutes of Health Stroke Scale score change from baseline to 90 days and the proportion of modified Rankin Scale (mRS)score ≤1 at 90 days after randomization. The secondary outcome included the decrease in inflammatory factors at 14 days. The primary safety outcome was the incidence of hemorrhagic transformation assessed according to Heidelberg bleeding classification within 7 days. A higher percentage of patients with HIHSS score ≤5 at 90 days in the EDV dexcamphorol group was observed than in the control group (75.36% vs 64.38%; <i>P</i> = 0.015). A higher percentage of patients with mRS score ≤1 at 90 days in the EDV dexcamphorol group was observed than in the control group (63.77% vs 50.68%; <i>P</i> = 0.012). After treatment, the levels of IL-6 and hs-CRP were significantly lower following treatment and compared to the control group (<i>P</i> < 0.05). In patients receiving the EDV dexborneol group, a significantly decreased risk of radiographic intracranial hemorrhage was found compared with the control group (20.29% vs 39.73%; <i>P</i> = 0.0006). In conclusion, EDV dexborneol can improve the clinical outcomes of patients with acute anterior circulation LVO stroke, which can be used as an effective supplement to thrombectomy therapy.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"14 1","pages":"20220312"},"PeriodicalIF":2.1,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10579784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49682701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroacupuncture inhibits the expression of HMGB1/RAGE and alleviates injury to the primary motor cortex in rats with cerebral ischemia.","authors":"Zeyin Nie,&nbsp;Huachun Miao,&nbsp;Chenyu Li,&nbsp;Feng Wu","doi":"10.1515/tnsci-2022-0316","DOIUrl":"10.1515/tnsci-2022-0316","url":null,"abstract":"<p><strong>Background: </strong>The high-mobility group box 1 (HMGB1)/receptor for advanced glycation end products (RAGE) signaling pathway holds promise as a potential therapeutic target for ischemic brain injury. The effects of FPS-ZM1 and electroacupuncture (EA) on activation of the HMGB1/RAGE signaling pathway after cerebral ischemia remain uncertain.</p><p><strong>Methods: </strong>Middle cerebral artery occlusion (MCAO) model was established. Neurological function was assessed using Longa scores. Nissl staining was used to observe the morphology of neurons. The expression levels of HMGB1 and RAGE were assayed with immunofluorescence staining and western blot.</p><p><strong>Results: </strong>The results showed that EA and FPS-ZM1 could reduce the neural function score and neurons cell injury in cerebral ischemia rats by inhibiting the expression of HMGB1 and RAGE in primary motor cortex (M1) region. In addition, EA combined with FPS-ZM1 had a better therapeutic effect.</p><p><strong>Conclusions: </strong>The HMGB1/RAGE pathway could be activated after cerebral ischemia. Both EA and FPS-ZM1 improved neurological deficits and attenuated neuronal damage in rats. They had synergistic effects. These interventions were observed to mitigate brain damage by suppressing the activation of HMGB1/RAGE.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"14 1","pages":"20220316"},"PeriodicalIF":2.1,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10566473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41213929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of γ-oryzanol on motor function in a spinal cord injury model.","authors":"ZhiYi Fan,&nbsp;WanDa Zhan,&nbsp;Jun Cai","doi":"10.1515/tnsci-2022-0310","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0310","url":null,"abstract":"<p><strong>Objective: </strong>Spinal cord injury (SCI) is caused by disease or trauma and results in a partial or complete loss of motor or sensory function below the injury level. Most patients with SCI are young, and long-term disability imposes both psychological and financial burdens. Rice is the most abundant source of γ-oryzanol, which exhibits both antioxidant and anti-inflammatory properties. γ-Oryzanol has been shown to cross the blood-brain barrier in an intact form and have beneficial effects on brain function. To the best of our knowledge, this is the first study to report the effect of γ-oryzanol on motor function recovery in mice after SCI.</p><p><strong>Methods: </strong>Mice were randomly divided into three groups: the sham group, the injury group, and the γ-oryzanol-treated group that received an intraperitoneal γ-oryzanol (100 mg/kg) injection every 2 days for 42 days after SCI. The effect of γ-oryzanol was assessed through various approaches. Behavioral tests were performed using Basso mouse scale scores and gait analysis. Hematoxylin and eosin staining, Luxol fast blue staining, magnetic resonance imaging ,and immunofluorescence staining were used to observe the lesion area changes, demyelination, axonal regeneration, and scar tissue formation. The levels of inflammatory cytokines in the peripheral blood of mice were assessed by enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>Behavioral tests showed that γ-oryzanol treatment improved gait following SCI. Pathological examination revealed that demyelination at the site of injury improved with γ-oryzanol treatment and was accompanied by the retention of axons associated with motor function and reduced scarring. Additionally, γ-oryzanol treatment decreased the serum levels of pro-inflammatory factors.</p><p><strong>Conclusions: </strong>Studies have shown that γ-oryzanol promotes motor function recovery in mice after SCI. Therefore, γ-oryzanol might be the latent target for SCI therapy.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"14 1","pages":"20220310"},"PeriodicalIF":2.1,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10512447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41172136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between RS3763040 polymorphism of the AQP4 and idiopathic intracranial hypertension in a Spanish Caucasian population.","authors":"Juan José Tellería-Orriols,&nbsp;Samsara López-Hernández,&nbsp;Inmaculada Vidriales-Vicente,&nbsp;Carlos Alberto Rodríguez-Arias","doi":"10.1515/tnsci-2022-0309","DOIUrl":"10.1515/tnsci-2022-0309","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic intracranial hypertension (IIH) is a condition of increased intracranial pressure of unknown aetiology. Principal symptoms are headache, visual disturbances, and obesity, together with elevated intracranial pressure. Unspecified MRI, despite normal ventricle size, suggests alterations in the water flux cellular mediated by the brain water channel aquaporin-4 (AQP4). The association among IIH, cerebral spinal fluid malfunction, reabsorption, and functional or regulatory modifications of AQP4 is a hypothesis not confirmed.</p><p><strong>Methods: </strong>Blood samples were collected from 72 Spanish Caucasian patients with IIH. A genetic association study was performed with bi-allelic SNPs rs1049305 and rs10244884 in AQ1 and rs2075575, rs3763043, and rs3763040 in AQ4. Genetic data were compared with 94 healthy Caucasian control. Statistics studies were assessed by Pearson's <i>χ</i> ² tests for 2 × 2 (alleles) or 3 × 2 (genotypes) contingency tables. A <i>P</i> value < 0.05 was considered to be statistically significant.</p><p><strong>Results: </strong>Statistically significant differences were found when comparing the results of the rs3763040 polymorphism of the AQ4 locus of IIH patients with controls, in genotypic frequencies (<i>P</i> = 0.0442) and allele frequencies (<i>P</i> = 0.0171). Furthermore, a statistically significant difference (<i>P</i> = 0.0207) was found in individuals carrying and not carrying the minor allele (GG + GA individuals vs GG homozygotes). No statistically significant differences were found when comparing allele and genotypic frequencies for SNPs rs1049305 and rs10244884 of AQ1 and rs2075575 and rs3763043 of AQ4.</p><p><strong>Conclusions: </strong>The association of AQP4 and specifically of its polymorphic variant rs3763040 with IIH should be validated in other ethnic groups in order to assess more precisely the role of AQP4 in the etiopathogenesis of IIH.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"14 1","pages":"20220309"},"PeriodicalIF":2.1,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10505302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10313086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroid hormone levels paradox in acute ischemic stroke.","authors":"Chunhui Xie, Yi Jiang, Xiaozhu Shen, Mengqian Liu, Yiwen Xu, Wen Zhong, Zhonglin Ge, Mingyue Qian, Nan Dong, Chen Gong, Guanghui Zhang","doi":"10.1515/tnsci-2022-0289","DOIUrl":"10.1515/tnsci-2022-0289","url":null,"abstract":"<p><strong>Objective: </strong>Accumulating evidence has suggested that thyroid hormone levels affect the prognosis of acute ischemic stroke (AIS), but the results have been inconsistent.</p><p><strong>Methods: </strong>Basic data, neural scale scores, thyroid hormone levels, and other laboratory examination data of AIS patients were collected. The patients were divided into excellent and poor prognosis group at discharge and 90 days after discharge. Logistic regression models were applied to evaluate the relationship between thyroid hormone levels and prognosis. A subgroup analysis was performed based on stroke severity.</p><p><strong>Results: </strong>A number of 441 AIS patients were included in this study. Those in the poor prognosis group were older, with higher blood sugar levels, higher free thyroxine (FT4) levels, and severe stroke (all <i>p</i> < 0.05) at baseline. Free thyroxine (FT4) showed a predictive value (all <i>p</i> < 0.05) for prognosis in the model adjusted for age, gender, systolic pressure, and glucose level. However, after adjustment for types and severity of stroke, FT4 showed insignificant associations. In the severe subgroup at discharge, the change in FT4 was statistically significant (<i>p</i> = 0.015), odds ratio (95% confidence interval) = 1.394 (1.068-1.820) but not in the other subgroups.</p><p><strong>Conclusions: </strong>High-normal FT4 serum levels in patients with severe stroke receiving conservative medical treatment at admission may indicate a worse short-term prognosis.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"14 1","pages":"20220289"},"PeriodicalIF":1.8,"publicationDate":"2023-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10251163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9673114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leptin ameliorates Aβ1-42-induced Alzheimer's disease by suppressing inflammation via activating p-Akt signaling pathway.","authors":"Lin Lu,&nbsp;Zijuan Fu,&nbsp;Bing Wu,&nbsp;Dongsen Zhang,&nbsp;Ying Wang","doi":"10.1515/tnsci-2022-0270","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0270","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is characterized by progressive neuronal loss, cognitive disorder, and memory decline. Leptin has been reported to have a neuroprotective effect on neurodegenerative diseases.</p><p><strong>Objective: </strong>Our aim was to investigate whether intraperitoneal injection of leptin has a neuroprotective effect and to explore its underlying mechanisms in the AD mouse model.</p><p><strong>Methods: </strong>Aβ1-42 was injected into male C57BL/6J mice to construct an AD mouse model, and leptin was injected intraperitoneally to cure AD. The Morris water maze test was used to investigate spatial learning ability. Neuronal loss was tested by tyrosine hydroxylase expression in the hippocampus, and terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling assay was applied to detect neuronal apoptosis. Pro-inflammatory cytokine levels were monitored by RT-PCR and western blotting was selected to explore which signaling pathway leptin acted on.</p><p><strong>Results: </strong>Leptin ameliorated spatial learning impairment, restored neuronal loss and apoptosis, and inhibited pro-inflammatory cytokine expression by activating the p-Akt signaling pathway in Aβ1-42-induced AD mice.</p><p><strong>Conclusion: </strong>Leptin ameliorates Aβ1-42-induced AD by suppressing inflammation via activating the p-Akt signaling pathway.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"14 1","pages":"20220270"},"PeriodicalIF":2.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10080705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9283533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIF-1α participates in secondary brain injury through regulating neuroinflammation.","authors":"Xiaojian Xu,&nbsp;Mengshi Yang,&nbsp;Bin Zhang,&nbsp;Jinqian Dong,&nbsp;Yuan Zhuang,&nbsp;Qianqian Ge,&nbsp;Fei Niu,&nbsp;Baiyun Liu","doi":"10.1515/tnsci-2022-0272","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0272","url":null,"abstract":"<p><p>A deeper understanding of the underlying biological mechanisms of secondary brain injury induced by traumatic brain injury (TBI) will greatly advance the development of effective treatments for patients with TBI. Hypoxia-inducible factor-1 alpha (HIF-1α) is a central regulator of cellular response to hypoxia. In addition, growing evidence shows that HIF-1α plays the important role in TBI-induced changes in biological processes; however, detailed functional mechanisms are not completely known. The aim of the present work was to further explore HIF-1α-mediated events after TBI. To this end, next-generation sequencing, coupled with cellular and molecular analysis, was adopted to interrogate vulnerable events in a rat controlled cortical impact model of TBI. The results demonstrated that TBI induced accumulation of HIF-1α at the peri-injury site at 24 h post-injury, which was associated with neuronal loss. Moreover, gene set enrichment analysis unveiled that neuroinflammation, especially an innate inflammatory response, was significantly evoked by TBI, which could be attenuated by the inhibition of HIF-1α. Furthermore, the inhibition of HIF-1α could mitigate the activation of microglia and astrocytes. Taken together, all these data implied that HIF-1α might contribute to secondary brain injury through regulating neuroinflammation.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"14 1","pages":"20220272"},"PeriodicalIF":2.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9921917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9314449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EHMT2 affects microglia polarization and aggravates neuronal damage and inflammatory response via regulating HMOX1.","authors":"Huaitao Yang,&nbsp;Zhifang Chen,&nbsp;Wenhong Gao","doi":"10.1515/tnsci-2022-0276","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0276","url":null,"abstract":"<p><strong>Objective: </strong>This research was designed to ascertain the function of euchromatic histone lysine methyltransferase 2 (EHMT2) in ischemic stroke-induced neuronal damage and inflammatory response and its regulatory mechanism.</p><p><strong>Methods: </strong>Mouse microglia (BV-2 cells) were induced by oxygen glucose deprivation/reoxygenation (OGD/R) to establish a cellular model, and then co-cultured with HT22 hippocampal neurons. After that, HT22 cell viability and apoptosis were evaluated, followed by the measurement of apoptosis-related factors (B-cell lymphoma-2, Bcl-2 associated X, and cleaved-Caspase 3). Meanwhile, the expression of inducible nitric oxide synthase (M1 microglia polarization marker) and arginase 1 (M2 microglia polarization marker) in BV-2 cells was detected, as well as the levels of inflammatory factors (tumor necrosis factor-α, interleukin [IL]-6, IL-10, IL-1β, and IL-4). Additionally, the expression of EHMT2 and heme oxygenase 1 (HMOX1) in BV-2 cells was assessed by quantitative reverse transcription polymerase chain reaction and western blot, and the binding between EHMT2 and HMOX1 was predicted and verified.</p><p><strong>Results: </strong>OGD/R treatment led to decreased cell viability and increased cell apoptosis in HT22 cells, and aggravated inflammatory response in BV-2 cells. In OGD/R-induced BV-2 cells, EHMT2 and HMOX1 were increasingly expressed, and knockdown of EHMT2 or HMOX1 in BV-2 cells could inhibit neuronal damage and inflammatory response. Moreover, EHMT2 promoted HMOX1 transcription level by histone methylation.</p><p><strong>Conclusion: </strong>Collected evidence showed that down-regulation of EHMT2 relieved neuronal damage and inflammatory response by inhibiting HMOX1 expression.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"14 1","pages":"20220276"},"PeriodicalIF":2.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10388136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9922872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hematoma evacuation based on active strategies versus conservative treatment in the management of moderate basal ganglia hemorrhage: A retrospective study.","authors":"Weihua Zhang,&nbsp;Jian Zhang,&nbsp;Gaoming Huang,&nbsp;Kaichuang Yang","doi":"10.1515/tnsci-2022-0292","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0292","url":null,"abstract":"<p><strong>Objective: </strong>The internal capsule of the basal ganglia is vulnerable to direct pressure from the hematoma and to secondary damage from toxic products of hemorrhage. Our study evaluated the risk and benefits of active strategies including ultra-early surgery and hematoma evacuation through a transsylvian-transinsular approach for moderate basal ganglia hemorrhage.</p><p><strong>Methods: </strong>We retrospectively collected patients with moderate basal ganglia hemorrhage in two hospitals. The conservative group contained 51 patients who had the best medical treatment, and the surgery group contained 36 patients who were treated with hematoma evacuation through a transsylvian-transinsular approach within 6 h from ictus. Motor function of upper and lower limbs recorded with the motor sub-score of NIHSS (m-NIHSS) at the baseline, 7 days, 30 days, and 90 days, the modified Rankin Scale (mRS), and Barthel Index (BI) scores at 30 and 90 days were compared between the two groups. Good recovery was defined as an m-NIHSS of 0-2 and poor recovery as 3-4. Favorable prognosis was defined as an mRS of 0-3 and unfavorable prognosis as 4-5.</p><p><strong>Results: </strong>The mean time from ictus to surgery was 250.3 ± 57.3 min. The good recovery proportions of upper and lower limbs in the surgery group were significantly higher than that in the conservative group (<i>p</i> < 0.05) at 7 days after hemorrhage. The good recovery proportion of upper limbs was significantly higher in the surgery group than in the conservative group (<i>p</i> < 0.05) at 3 months after hemorrhage. Living ability using BI scores was significantly higher in the surgery group than the conservative group (<i>p</i> < 0.05) at 3 months after hemorrhage. The favorable prognosis proportion had no statistically significant difference between the two groups at 3 months after hemorrhage.</p><p><strong>Conclusions: </strong>Ultra-early hematoma evacuation through a transsylvian-transinsular approach are active strategies for moderate basal ganglia hemorrhage and have potential advantages in improving motor function recovery and daily living. The postoperative rebleeding rate does not increase simultaneously.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"14 1","pages":"20220292"},"PeriodicalIF":2.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10388134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9922875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The promoting effect of modified Dioscorea pills on vascular remodeling in chronic cerebral hypoperfusion via the Ang/Tie signaling pathway.","authors":"Guiying Kuang,&nbsp;Zhigang Shu,&nbsp;Chunli Zhu,&nbsp;Hongbing Li,&nbsp;Cheng Zhang","doi":"10.1515/tnsci-2022-0302","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0302","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to investigate the effect of modified Dioscorea pills (MDP) on microcirculatory remodeling in the hippocampus of rats with chronic cerebral hypoperfusion (CCH) through the angiopoietin (Ang)/tyrosine kinase receptor tyrosine kinase with immunoglobulin-like and EGF-like domains (Ang receptor) 2 (Tie-2) signaling pathways, which may underlie the cognitive improvement observed in CCH rats.</p><p><strong>Methods: </strong>Forty male Sprague-Dawley rats raised under specific pathogen-free conditions were randomly divided into three groups: control group (10 rats), model group (15 rats), and MDP group (15 rats). The rats in the model group and MDP group underwent bilateral common carotid artery occlusion using the 2-vessel occlusion (2-VO) method to induce CCH. Rats in the control group underwent the same surgical procedures as those in the model group, except for ligation and occlusion of the carotid arteries. After 1 week of 2-VO, rats in the MDP group were administered MDP condensed decoction intragastrically at a dose of 1 ml/100 g body weight (prepared by the Preparation Room of Hubei Provincial Hospital of Traditional Chinese Medicine) for 45 days, while rats in the other two groups received normal saline intragastrically with the same dose and duration as the MDP group. After the intervention, all rats were euthanized, and brain perfusion was performed to obtain the hippocampal tissue for analysis. Immunohistochemical staining for CD43 was performed to assess microvessel density (MVD); western blot and the reverse transcription-polymerase chain reaction (RT-PCR) were used to analyze the expression of proteins and genes in angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), Tie-2, and vascular endothelial growth factor (VEGF) proteins and genes in the hippocampal tissue and compute the Ang-1/Ang-2 ratio.</p><p><strong>Results: </strong>MDP treatment reduced neuronal loss and promoted restoration of the damaged hippocampal structure in CCH rats. The model group showed significantly higher MVD (14.93 ± 1.92) compared to the control group (5.78 ± 1.65) (<i>P</i> < 0.01), whereas MDP treatment further increased MVD (21.19 ± 2.62). Western blot and RT-PCR analysis revealed that CCH significantly increased the expression of Ang-1, Ang-2, Tie-2, and VEGF proteins and genes, while MDP treatment further significantly upregulated the expression of these proteins and genes. In addition, MDP significantly elevated the gene and protein expression of the Ang-1/Ang-2 ratio compared to the control group (<i>P</i> = 0.041, <i>P</i> = 0.029).</p><p><strong>Conclusion: </strong>CCH induces microvascular neogenesis in the hippocampus, and MDP promotes angiogenesis and microcirculation remodeling in CCH rats via the Ang/Tie signaling pathway, which may be an important mechanism for its restorative effects on hippocampal perfusion and improvement of cognitive function in CCH rats.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"14 1","pages":"20220302"},"PeriodicalIF":2.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10448306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10481841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}