Pub Date : 2024-01-01DOI: 10.2174/0115672026304601240307051654
Gustavo da Fontoura Galvão, Ricardo Castro Filho, Alexandre Alexandre Martins Cunha, Andre Guimarães Soares, Marcos Antônio Dellaretti Filho, Jorge Marcondes de Souza
Background: Cerebral Cavernous Malformation (CCM) is one of the most common types of vascular malformation of the central nervous system. Intracerebral hemorrhage, seizures, and lesional growth are the main clinical manifestations. Natural history studies have tried to identify many risk factors; however, the clinical course remains highly unpredictable.
Objective: Here, we have analyzed a multicenter CCM cohort looking for the differential clinical data regarding the patients harboring supra and/or infratentorial cavernous malformations in order to better understand risk factors involved in the anatomical location of the unique neurosurgical disease.
Methods: We have presented a multicenter, Propensity Score Matched (PSM), case-control study including 149 consecutive CCM cases clinically evaluated from May 2017 to December 2022 from three different neurosurgical centers. Epidemiological data were defined at each clinical assessment. Logistic regression was used to identify the independent contribution of each possible risk factor to the bleeding risk. To balance baseline covariates between patients with and without symptoms, and specifically between those with and without symptomatic bleeding, we used a PSM strategy. The Kaplan-Meier curve was drawn to evaluate if patients with infratentorial lesions had a greater chance of bleeding earlier in their life.
Results: The presence of infratentorial lesions was a risk factor in the multivariate analysis comparing the bleeding risk with pure asymptomatic individuals (OR: 3.23, 95% CI 1.43 - 7.26, P = 0.005). Also, having an infratentorial CCM was a risk factor after PSM (OR: 4.56, 95% CI 1.47 - 14.10, P = 0.008). The presence of an infratentorial lesion was related to precocity of symptoms when the time to first bleed was compared to all other clinical presentations in the overall cohort (P = 0.0328) and in the PSM group (P = 0.03).
Conclusion: Here, we have provided some evidence that infratentorial cerebral cavernous malformation may have a more aggressive clinical course, being a risk factor for symptomatic haemorrhage and precocity of bleeding.
{"title":"Infratentorial Cerebral Cavernous Malformation May be a Risk Factor for Symptomatic Bleeding and Precocity of Symptoms: A Multicenter, Propensity Score Matched, Case-Control Study.","authors":"Gustavo da Fontoura Galvão, Ricardo Castro Filho, Alexandre Alexandre Martins Cunha, Andre Guimarães Soares, Marcos Antônio Dellaretti Filho, Jorge Marcondes de Souza","doi":"10.2174/0115672026304601240307051654","DOIUrl":"10.2174/0115672026304601240307051654","url":null,"abstract":"<p><strong>Background: </strong>Cerebral Cavernous Malformation (CCM) is one of the most common types of vascular malformation of the central nervous system. Intracerebral hemorrhage, seizures, and lesional growth are the main clinical manifestations. Natural history studies have tried to identify many risk factors; however, the clinical course remains highly unpredictable.</p><p><strong>Objective: </strong>Here, we have analyzed a multicenter CCM cohort looking for the differential clinical data regarding the patients harboring supra and/or infratentorial cavernous malformations in order to better understand risk factors involved in the anatomical location of the unique neurosurgical disease.</p><p><strong>Methods: </strong>We have presented a multicenter, Propensity Score Matched (PSM), case-control study including 149 consecutive CCM cases clinically evaluated from May 2017 to December 2022 from three different neurosurgical centers. Epidemiological data were defined at each clinical assessment. Logistic regression was used to identify the independent contribution of each possible risk factor to the bleeding risk. To balance baseline covariates between patients with and without symptoms, and specifically between those with and without symptomatic bleeding, we used a PSM strategy. The Kaplan-Meier curve was drawn to evaluate if patients with infratentorial lesions had a greater chance of bleeding earlier in their life.</p><p><strong>Results: </strong>The presence of infratentorial lesions was a risk factor in the multivariate analysis comparing the bleeding risk with pure asymptomatic individuals (OR: 3.23, 95% CI 1.43 - 7.26, P = 0.005). Also, having an infratentorial CCM was a risk factor after PSM (OR: 4.56, 95% CI 1.47 - 14.10, P = 0.008). The presence of an infratentorial lesion was related to precocity of symptoms when the time to first bleed was compared to all other clinical presentations in the overall cohort (P = 0.0328) and in the PSM group (P = 0.03).</p><p><strong>Conclusion: </strong>Here, we have provided some evidence that infratentorial cerebral cavernous malformation may have a more aggressive clinical course, being a risk factor for symptomatic haemorrhage and precocity of bleeding.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"177-183"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Early neurological deterioration (END) after bridging therapy (BT) of acute ischemic stroke (AIS) patients is associated with poor outcomes.
Objective: We aimed to study the incidence, risk factors and prognosis of END after BT.
Methods: From January to December 2021, the clinical data of AIS patients treated by BT (intravenous thrombolysis with alteplase prior to mechanical thrombectomy) from three comprehensive stroke centers were analyzed. Patients were divided into non-END group and END group according to whether they developed END within 72 hours of symptom onset. Modified Rankin scale (mRS) was used to assess the patient's prognosis at 90 days, and favorable outcomes were defined as mRS≤2. The incidence of END was investigated, and binary logistic regression analysis was used to explore its associated factors.
Results: The incidence of END after BT was 33.67%. The eligible 90 patients included 29 cases in the END group and 61 cases in the non-END group. Multivariate Logistic regression analysis showed that increase of systolic blood pressure (SBP) (OR=1.026, 95%CI:1.001-1.051, p =0.043), higher level of blood glucose at admission (OR=1.389, 95%CI:1.092-1.176, p =0.007) and large artery atherosclerosis (LAA) subtype (OR=8.009, 95%CI:2.357-27.223, p =0.001) were independent risk factors of END. Compared with the non-END group, the END group had significantly lower rates of good outcomes (6.90% versus 65.57%, p =0.001) while higher rates of mortality (44.83% versus 4.92%, p =0.001).
Conclusion: It was found that the incidence of END after BT in AIS patients was 33.67%. An increase in SBP, higher glucose levels at admission, and LAA were independent risk factors of END that predicted a poor prognosis.
{"title":"Risk Factors and Prognosis of Early Neurological Deterioration after Bridging Therapy.","authors":"Yiju Xie, Shengyu Li, Liuyu Liu, Shiting Tang, Yayuan Liu, Shuangquan Tan, Zhijian Liang","doi":"10.2174/0115672026287986240104074006","DOIUrl":"10.2174/0115672026287986240104074006","url":null,"abstract":"<p><strong>Background: </strong>Early neurological deterioration (END) after bridging therapy (BT) of acute ischemic stroke (AIS) patients is associated with poor outcomes.</p><p><strong>Objective: </strong>We aimed to study the incidence, risk factors and prognosis of END after BT.</p><p><strong>Methods: </strong>From January to December 2021, the clinical data of AIS patients treated by BT (intravenous thrombolysis with alteplase prior to mechanical thrombectomy) from three comprehensive stroke centers were analyzed. Patients were divided into non-END group and END group according to whether they developed END within 72 hours of symptom onset. Modified Rankin scale (mRS) was used to assess the patient's prognosis at 90 days, and favorable outcomes were defined as mRS≤2. The incidence of END was investigated, and binary logistic regression analysis was used to explore its associated factors.</p><p><strong>Results: </strong>The incidence of END after BT was 33.67%. The eligible 90 patients included 29 cases in the END group and 61 cases in the non-END group. Multivariate Logistic regression analysis showed that increase of systolic blood pressure (SBP) (OR=1.026, 95%CI:1.001-1.051, p =0.043), higher level of blood glucose at admission (OR=1.389, 95%CI:1.092-1.176, p =0.007) and large artery atherosclerosis (LAA) subtype (OR=8.009, 95%CI:2.357-27.223, p =0.001) were independent risk factors of END. Compared with the non-END group, the END group had significantly lower rates of good outcomes (6.90% versus 65.57%, p =0.001) while higher rates of mortality (44.83% versus 4.92%, p =0.001).</p><p><strong>Conclusion: </strong>It was found that the incidence of END after BT in AIS patients was 33.67%. An increase in SBP, higher glucose levels at admission, and LAA were independent risk factors of END that predicted a poor prognosis.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"25-31"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139682161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0115672026298727240219110134
Yongho Kwon, Ho Jun Yi, Dong-Seong Shin, Bum-Tae Kim
Objective: Emboli commonly occurs in mechanical thrombectomy (MT). The objective of this study was to analyze predicting factors of emboli after MT.
Methods: Patients who underwent MT with successful reperfusion for anterior circulation occlusion were enrolled. Emboli included distal emboli at digital subtraction angiography (DSA) and unexpected embolic infarct on diffusion-weighted image (DWI) without distal emboli at DSA. Baseline characteristics, procedural details, angiographic outcomes, and clinical outcomes were reviewed. Multivariable analyses were performed to evaluate predictive factors for the occurrence of emboli.
Results: Of 601 patients, 149 (24.8%) patients had distal emboli at DSA, and 169 (28.1%) patients had unexpected embolic infarction on DWI even without distal emboli at DSA. A total of 318 (52.9%) patients were enrolled in the embolic group, and 283 (47.1%) patients were assigned to the non-embolic group. In multivariate analysis, larger microcatheter (OR 1.26, 95% CI 1.12-1.94; p = 0.047), clot passage (OR 1.33, 95% CI 1.07-1.87; p = 0.041), use of balloon guide catheter (BGC) (OR 0.70, 95% CI 0.52-0.92; p = 0.014), early ballooning of BGC (OR 0.68, 95% CI 0.50-0.90; p = 0.009), and longer stent retriever (OR 0.72, 95% CI 0.54-0.90; p = 0.029) were associated with occurrence of emboli.
Conclusion: MT with only a stent retriever, use of a larger microcatheter, and clot passage might increase the risk of emboli. In contrast, contact aspiration thrombectomy, use of BGC, early ballooning of BGC, and use of longer stent retrievers could reduce the chance of emboli.
{"title":"Predictors of Emboli in Mechanical Thrombectomy for Anterior Circulation Stroke.","authors":"Yongho Kwon, Ho Jun Yi, Dong-Seong Shin, Bum-Tae Kim","doi":"10.2174/0115672026298727240219110134","DOIUrl":"10.2174/0115672026298727240219110134","url":null,"abstract":"<p><strong>Objective: </strong>Emboli commonly occurs in mechanical thrombectomy (MT). The objective of this study was to analyze predicting factors of emboli after MT.</p><p><strong>Methods: </strong>Patients who underwent MT with successful reperfusion for anterior circulation occlusion were enrolled. Emboli included distal emboli at digital subtraction angiography (DSA) and unexpected embolic infarct on diffusion-weighted image (DWI) without distal emboli at DSA. Baseline characteristics, procedural details, angiographic outcomes, and clinical outcomes were reviewed. Multivariable analyses were performed to evaluate predictive factors for the occurrence of emboli.</p><p><strong>Results: </strong>Of 601 patients, 149 (24.8%) patients had distal emboli at DSA, and 169 (28.1%) patients had unexpected embolic infarction on DWI even without distal emboli at DSA. A total of 318 (52.9%) patients were enrolled in the embolic group, and 283 (47.1%) patients were assigned to the non-embolic group. In multivariate analysis, larger microcatheter (OR 1.26, 95% CI 1.12-1.94; <i>p</i> = 0.047), clot passage (OR 1.33, 95% CI 1.07-1.87; <i>p</i> = 0.041), use of balloon guide catheter (BGC) (OR 0.70, 95% CI 0.52-0.92; <i>p</i> = 0.014), early ballooning of BGC (OR 0.68, 95% CI 0.50-0.90; <i>p</i> = 0.009), and longer stent retriever (OR 0.72, 95% CI 0.54-0.90; <i>p</i> = 0.029) were associated with occurrence of emboli.</p><p><strong>Conclusion: </strong>MT with only a stent retriever, use of a larger microcatheter, and clot passage might increase the risk of emboli. In contrast, contact aspiration thrombectomy, use of BGC, early ballooning of BGC, and use of longer stent retrievers could reduce the chance of emboli.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"131-138"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Electroacupuncture (EA) treatment plays a protective role in cerebral ischemiareperfusion (CIR) injury. However, the underlying molecular mechanism is still not fully elucidated.
Methods: All rats were randomly divided into five groups: the SHAM group, MCAO group, MCAO+EA (MEA) group, MCAO+METTL3 overexpression+EA (METTL3) group and MCAO+lncRNA H19 overexpression+EA (lncRNA H19) group. The middle cerebral artery occlusion (MCAO) rats were established to mimic CIR injury. The overexpression of lncRNA H19 and METTL3 was induced by stereotactic injection of lentiviruses into the rat lateral ventricles. The rats in the MEA, METTL3, and lncRNA H19 groups were treated with EA therapy on "Renzhong" (DU26) and "Baihui" (DU20) acupoints (3.85/6.25Hz; 1mA). Besides, the neurological deficit scoring, cerebral infarction area, pathological changes in brain tissue, total RNA m6A level, and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 were detected in this experiment.
Results: EA improved the neurological deficit scoring, cerebral infarction area, and pathological injury in MCAO rats, while these beneficial effects of EA on CIR injury were attenuated by the overexpression of METTL3 or lncRNA H19. More importantly, EA down-regulated the total RNA m6A level and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 in MCAO rats. Instead, the overexpression of METTL3 or lncRNA H19 was found to reverse the EA-induced down-regulation.
Conclusion: The findings indicated that EA might down-regulate the S1PR2/TLR4/NLRP3 signaling pathway via m6A methylation of lncRNA H19 to alleviate CIR injury. Our findings provide a new insight into the molecular mechanism of EA on CIR injury.
{"title":"Electroacupuncture Alleviates Cerebral Ischemia-reperfusion Injury by Regulating the S1PR2/TLR4/NLRP3 Signaling Pathway via m6A Methylation of lncRNA H19.","authors":"Han-Rui Zhang, Gu-Quan Ma, He-Qun Lv, Yao-Ting Feng, Yong-Jun Peng","doi":"10.2174/0115672026294183240207115956","DOIUrl":"10.2174/0115672026294183240207115956","url":null,"abstract":"<p><p>Electroacupuncture (EA) treatment plays a protective role in cerebral ischemiareperfusion (CIR) injury. However, the underlying molecular mechanism is still not fully elucidated.</p><p><strong>Methods: </strong>All rats were randomly divided into five groups: the SHAM group, MCAO group, MCAO+EA (MEA) group, MCAO+METTL3 overexpression+EA (METTL3) group and MCAO+lncRNA H19 overexpression+EA (lncRNA H19) group. The middle cerebral artery occlusion (MCAO) rats were established to mimic CIR injury. The overexpression of lncRNA H19 and METTL3 was induced by stereotactic injection of lentiviruses into the rat lateral ventricles. The rats in the MEA, METTL3, and lncRNA H19 groups were treated with EA therapy on \"Renzhong\" (DU26) and \"Baihui\" (DU20) acupoints (3.85/6.25Hz; 1mA). Besides, the neurological deficit scoring, cerebral infarction area, pathological changes in brain tissue, total RNA m6A level, and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 were detected in this experiment.</p><p><strong>Results: </strong>EA improved the neurological deficit scoring, cerebral infarction area, and pathological injury in MCAO rats, while these beneficial effects of EA on CIR injury were attenuated by the overexpression of METTL3 or lncRNA H19. More importantly, EA down-regulated the total RNA m6A level and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 in MCAO rats. Instead, the overexpression of METTL3 or lncRNA H19 was found to reverse the EA-induced down-regulation.</p><p><strong>Conclusion: </strong>The findings indicated that EA might down-regulate the S1PR2/TLR4/NLRP3 signaling pathway via m6A methylation of lncRNA H19 to alleviate CIR injury. Our findings provide a new insight into the molecular mechanism of EA on CIR injury.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"64-73"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Glioblastoma multiforme (GBM) is an aggressive type of brain tumor that is difficult to remove surgically. Research suggests that substances from saffron, namely crocetin and crocin, could be effective natural treatments, showing abilities to kill cancer cells.
Methods: Our study focused on evaluating the effects of crocetin on glioma using the U87 cell line. We specifically investigated how crocetin affects the survival, growth, and spread of glioma cells, exploring its impact at concentrations ranging from 75-150 μM. The study also included experiments combining crocetin with the chemotherapy drug Temozolomide (TMZ) to assess potential synergistic effects.
Results: Crocetin significantly reduced the viability, proliferation, and migration of glioma cells. It achieved these effects by decreasing the levels of Matrix Metallopeptidase 9 (MMP-9) and Ras homolog family member A (RhoA), proteins that are critical for cancer progression. Additionally, crocetin inhibited the formation of cellular structures necessary for tumor growth. It blocked multiple points of the Ak Strain Transforming (AKT) signaling pathway, which is vital for cancer cell survival. This treatment led to increased cell death and disrupted the cell cycle in the glioma cells. When used in combination with TMZ, crocetin not only enhanced the reduction of cancer cell growth but also promoted cell death and reduced cell replication. This combination therapy further decreased levels of high mobility group box 1 (HMGB1) and Receptor for Advanced Glycation End-products (RAGE), proteins linked to inflammation and tumor progression. It selectively inhibited certain pathways involved in the cellular stress response without affecting others.
Conclusion: Our results underscore the potential of crocetin as a treatment for glioma. It targets various mechanisms involved in tumor growth and spread, offering multiple avenues for therapy. Further studies are essential to fully understand and utilize crocetin's benefits in treating glioma.
{"title":"Crocetin Enhances Temozolomide Efficacy in Glioblastoma Therapy Through Multiple Pathway Suppression.","authors":"Wei-En Tsai, Yen-Tsen Liu, Fu-Hsuan Kuo, Wen-Yu Cheng, Chiung-Chyi Shen, Ming-Tsang Chiao, Yu-Fen Huang, Yea-Jiuen Liang, Yi-Chin Yang, Wan-Yu Hsieh, Jun-Peng Chen, Szu-Yuan Liu, Cheng-Di Chiu","doi":"10.2174/0115672026332275240731054001","DOIUrl":"10.2174/0115672026332275240731054001","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma multiforme (GBM) is an aggressive type of brain tumor that is difficult to remove surgically. Research suggests that substances from saffron, namely crocetin and crocin, could be effective natural treatments, showing abilities to kill cancer cells.</p><p><strong>Methods: </strong>Our study focused on evaluating the effects of crocetin on glioma using the U87 cell line. We specifically investigated how crocetin affects the survival, growth, and spread of glioma cells, exploring its impact at concentrations ranging from 75-150 μM. The study also included experiments combining crocetin with the chemotherapy drug Temozolomide (TMZ) to assess potential synergistic effects.</p><p><strong>Results: </strong>Crocetin significantly reduced the viability, proliferation, and migration of glioma cells. It achieved these effects by decreasing the levels of Matrix Metallopeptidase 9 (MMP-9) and Ras homolog family member A (RhoA), proteins that are critical for cancer progression. Additionally, crocetin inhibited the formation of cellular structures necessary for tumor growth. It blocked multiple points of the Ak Strain Transforming (AKT) signaling pathway, which is vital for cancer cell survival. This treatment led to increased cell death and disrupted the cell cycle in the glioma cells. When used in combination with TMZ, crocetin not only enhanced the reduction of cancer cell growth but also promoted cell death and reduced cell replication. This combination therapy further decreased levels of high mobility group box 1 (HMGB1) and Receptor for Advanced Glycation End-products (RAGE), proteins linked to inflammation and tumor progression. It selectively inhibited certain pathways involved in the cellular stress response without affecting others.</p><p><strong>Conclusion: </strong>Our results underscore the potential of crocetin as a treatment for glioma. It targets various mechanisms involved in tumor growth and spread, offering multiple avenues for therapy. Further studies are essential to fully understand and utilize crocetin's benefits in treating glioma.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"320-336"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0115672026290996240307072539
Jing-Xuan Li, Dai Shi, Si-Ying Ren, Guo-Feng Wu
Background: Drug-resistant epilepsy (DRE) is a refractory neurological disorder. There is ample evidence that suggest that γ-aminobutyric acid-a (GABAA) receptors could be one of the mechanisms responsible for the development of drug resistance in epilepsy. It is also known that the cAMP response element binding protein (CREB) plays a possible key role in the transcriptional regulation of GABAA.
Objective: This study explores the role of CREB in the development of DRE and the effect of CREB on GABA-related receptors in DRE.
Methods: The CREB expression was increased or decreased in the hippocampus of normal rats by lentiviral transfection, who then underwent the lithium-pilocarpine-induced epilepsy model. Phenobarbital (PB) sodium and carbamazepine (CBZ) were used to select a drug-resistant epileptic model. The expression levels of GABAA receptor α1, β2, and γ2 subunits and CREB protein were measured in the rat hippocampus by western blot and fluorescent quantitative PCR.
Results: The frequency and duration of seizures increased in the overexpression group compared to that in the control group. In addition, the severity, frequency, and duration of seizures decreased in the group with decreased expression. The hippocampus analysis of the expression levels of the CREB protein and CREB mRNA yielded similar findings. Altering the CREB protein expression in the rat hippocampus could negatively regulate the expression and transcript levels of GABAA receptors α1, β2, and γ2, suggesting that CREB may serve as a potential target for the development of treatment protocols and drugs for epilepsy.
Conclusion: Our study shows that enhanced CREB expression promotes the development of DRE and negatively regulates GABAA receptor levels and that the inhibition of CREB expression may reduce the incidence of DRE.
背景:耐药性癫痫(DRE)是一种难治性神经系统疾病。大量证据表明,γ-氨基丁酸-a(GABAA)受体可能是导致癫痫耐药性产生的机制之一。人们还知道,cAMP 反应元件结合蛋白(CREB)在 GABAA 的转录调控中可能起着关键作用:本研究探讨了 CREB 在 DRE 发病中的作用,以及 CREB 对 DRE 中 GABA 相关受体的影响:方法:通过慢病毒转染增加或减少正常大鼠海马中CREB的表达,然后对其进行锂-匹罗卡品诱导的癫痫模型试验。苯巴比妥钠(PB)和卡马西平(CBZ)用于选择耐药癫痫模型。通过Western印迹和荧光定量PCR检测大鼠海马中GABAA受体α1、β2和γ2亚基以及CREB蛋白的表达水平:结果:与对照组相比,过表达组大鼠癫痫发作的频率和持续时间增加。此外,表达减少组的癫痫发作严重程度、频率和持续时间均有所下降。对海马CREB蛋白和CREB mRNA表达水平的分析也得出了类似的结果。改变大鼠海马中CREB蛋白的表达可负向调节GABAA受体α1、β2和γ2的表达和转录水平,这表明CREB可能是开发癫痫治疗方案和药物的潜在靶点:我们的研究表明,CREB表达的增强会促进DRE的发生,并负向调节GABAA受体水平,抑制CREB的表达可降低DRE的发病率。
{"title":"Increased Cyclic Adenosine Monophosphate Responsive Element is Closely Associated with the Pathogenesis of Drug-resistant Epilepsy.","authors":"Jing-Xuan Li, Dai Shi, Si-Ying Ren, Guo-Feng Wu","doi":"10.2174/0115672026290996240307072539","DOIUrl":"10.2174/0115672026290996240307072539","url":null,"abstract":"<p><strong>Background: </strong>Drug-resistant epilepsy (DRE) is a refractory neurological disorder. There is ample evidence that suggest that γ-aminobutyric acid-a (GABAA) receptors could be one of the mechanisms responsible for the development of drug resistance in epilepsy. It is also known that the cAMP response element binding protein (CREB) plays a possible key role in the transcriptional regulation of GABA<sub>A</sub>.</p><p><strong>Objective: </strong>This study explores the role of CREB in the development of DRE and the effect of CREB on GABA-related receptors in DRE.</p><p><strong>Methods: </strong>The CREB expression was increased or decreased in the hippocampus of normal rats by lentiviral transfection, who then underwent the lithium-pilocarpine-induced epilepsy model. Phenobarbital (PB) sodium and carbamazepine (CBZ) were used to select a drug-resistant epileptic model. The expression levels of GABA<sub>A</sub> receptor α1, β2, and γ2 subunits and CREB protein were measured in the rat hippocampus by western blot and fluorescent quantitative PCR.</p><p><strong>Results: </strong>The frequency and duration of seizures increased in the overexpression group compared to that in the control group. In addition, the severity, frequency, and duration of seizures decreased in the group with decreased expression. The hippocampus analysis of the expression levels of the CREB protein and CREB mRNA yielded similar findings. Altering the CREB protein expression in the rat hippocampus could negatively regulate the expression and transcript levels of GABA<sub>A</sub> receptors α1, β2, and γ2, suggesting that CREB may serve as a potential target for the development of treatment protocols and drugs for epilepsy.</p><p><strong>Conclusion: </strong>Our study shows that enhanced CREB expression promotes the development of DRE and negatively regulates GABA<sub>A</sub> receptor levels and that the inhibition of CREB expression may reduce the incidence of DRE.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"54-63"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140103017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0115672026298542240130053315
Dandan Geng, Huanxian Liu, Haoyuan Wang, Zhao Dong, Hebo Wang
Background: Migraine is implicated in oxidative stress. The oxidative balance score (OBS) assesses the combined impact of diet and lifestyle on oxidative and antioxidant balance in diseases. However, the association between OBS and migraine remains underexplored.
Objective: We aimed to examine the relationship between OBS and severe headaches or migraines among American adults.
Methods: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, defining severe headaches or migraine via self-reports and calculating OBS from 16 diaries and 4 lifestyle factors. Multivariable weighted logistic regression models were used to explore the OBS-migraine relationship, with stratified analysis for result validation.
Results: The study included 6,653 participants (average age 45.6, 52.1% male), and 19.1% reported severe headaches or migraines. There was a significant inverse association between OBS and severe headache or migraine, with an adjusted odds ratio (OR) of 0.97 (95% [confidence interval] CI: 0.96, 0.98, p < 0.001). The highest OBS tertile had an adjusted OR of 0.58 (95% CI: 0.47, 0.73) compared to the lowest. This pattern was consistent across sexes, with an adjusted OR of 0.98 (0.95, 1.00) in males and 0.97 (0.95, 1.00) in females. The adjusted OR for migraine was 0.61 (0.44, 0.87) and 0.54 (0.37, 0.79) in the highest tertile for males and females, respectively.
Conclusion: The study highlights a significant association between OBS and severe headaches or migraines, suggesting the potential role of oxidative stress in these conditions. The findings emphasize the importance of a balanced, antioxidant-rich diet and lifestyle in managing severe headaches or migraine.
{"title":"Association between Oxidative Balance Score and Severe Headache or Migraine among American Adults A Cross-Section Study.","authors":"Dandan Geng, Huanxian Liu, Haoyuan Wang, Zhao Dong, Hebo Wang","doi":"10.2174/0115672026298542240130053315","DOIUrl":"10.2174/0115672026298542240130053315","url":null,"abstract":"<p><strong>Background: </strong>Migraine is implicated in oxidative stress. The oxidative balance score (OBS) assesses the combined impact of diet and lifestyle on oxidative and antioxidant balance in diseases. However, the association between OBS and migraine remains underexplored.</p><p><strong>Objective: </strong>We aimed to examine the relationship between OBS and severe headaches or migraines among American adults.</p><p><strong>Methods: </strong>This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, defining severe headaches or migraine <i>via</i> self-reports and calculating OBS from 16 diaries and 4 lifestyle factors. Multivariable weighted logistic regression models were used to explore the OBS-migraine relationship, with stratified analysis for result validation.</p><p><strong>Results: </strong>The study included 6,653 participants (average age 45.6, 52.1% male), and 19.1% reported severe headaches or migraines. There was a significant inverse association between OBS and severe headache or migraine, with an adjusted odds ratio (OR) of 0.97 (95% [confidence interval] CI: 0.96, 0.98, p < 0.001). The highest OBS tertile had an adjusted OR of 0.58 (95% CI: 0.47, 0.73) compared to the lowest. This pattern was consistent across sexes, with an adjusted OR of 0.98 (0.95, 1.00) in males and 0.97 (0.95, 1.00) in females. The adjusted OR for migraine was 0.61 (0.44, 0.87) and 0.54 (0.37, 0.79) in the highest tertile for males and females, respectively.</p><p><strong>Conclusion: </strong>The study highlights a significant association between OBS and severe headaches or migraines, suggesting the potential role of oxidative stress in these conditions. The findings emphasize the importance of a balanced, antioxidant-rich diet and lifestyle in managing severe headaches or migraine.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"139-147"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139699120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0115672026312548240610104504
Pikria Ketelauri, Meltem Gümüs, Hanah Hadice Gull, Maryam Said, Laurel Rauschenbach, Thiemo Florin Dinger, Mehdi Chihi, Marvin Darkwah Oppong, Yahya Ahmadipour, Philipp Dammann, Karsten Henning Wrede, Ulrich Sure, Ramazan Jabbarli
Objective: A rupture of the intracranial aneurysm is frequently complicated, with an increase of intracranial pressure (ICP) requiring conservative and/or surgical treatment. We analyzed the risk factors related to the duration of pathologic ICP increase and the relationship between ICP burden and the outcome of subarachnoid hemorrhage (SAH).
Methods: Consecutive cases with aneurysmal SAH treated at our institution between 01/2003 and 06/2016 were eligible for this study. Different admission variables were evaluated to predict the duration of ICP increase >20 mmHg in univariate and multivariate analyses. The association of the ICP course with SAH outcome parameters (risk of cerebral infarction, in-hospital mortality, and unfavorable outcome at 6 months defined as modified Rankin scale >3) was adjusted for major outcome-relevant confounders.
Results: Of 820 SAH patients, 378 individuals (46.1%) developed at least one ICP increase requiring conservative and/or surgical management after aneurysm treatment (mean duration: 1.76 days, range: 1 - 14 days). In the multivariable linear regression analysis, patients' age (unstandardized coefficient [UC]=-0.02, p <0.0001), World Federation of Neurosurgical Societies (WFNS) grade 4-5 at admission (UC=0.71, p <0.004), regular medication with the angiotensinconverting enzyme (ACE) inhibitors (UC=-0.61, p =0.01), and presence of intracerebral hemorrhage (UC=0.59, p =0.002) were associated with the duration of ICP increase. In turn, patients with longer ICP elevations were at higher risk for cerebral infarction (adjusted odds ratio [aOR]=1.32 per-day-increase, p <0.0001), in-hospital mortality (aOR=1.30, p <0.0001) and unfavorable outcome (aOR=1.43, p <0.0001). SAH patients who underwent primary decompressive craniectomy (DC) showed shorter periods of ICP increase than patients with a secondary decompression (mean: 2.8 vs 4.9 days, p <0.0001).
Conclusion: The duration of ICP increase after aneurysm rupture is a strong outcome predictor and is related to younger age and higher initial severity of SAH. Further analysis of the factors impacting the course of ICP after SAH is essential for the optimization of ICP management and outcome improvement.
{"title":"Duration of Intracranial Pressure Increase after Aneurysmal Subarachnoid Hemorrhage: Prognostic Factors and Association with the Outcome.","authors":"Pikria Ketelauri, Meltem Gümüs, Hanah Hadice Gull, Maryam Said, Laurel Rauschenbach, Thiemo Florin Dinger, Mehdi Chihi, Marvin Darkwah Oppong, Yahya Ahmadipour, Philipp Dammann, Karsten Henning Wrede, Ulrich Sure, Ramazan Jabbarli","doi":"10.2174/0115672026312548240610104504","DOIUrl":"10.2174/0115672026312548240610104504","url":null,"abstract":"<p><strong>Objective: </strong>A rupture of the intracranial aneurysm is frequently complicated, with an increase of intracranial pressure (ICP) requiring conservative and/or surgical treatment. We analyzed the risk factors related to the duration of pathologic ICP increase and the relationship between ICP burden and the outcome of subarachnoid hemorrhage (SAH).</p><p><strong>Methods: </strong>Consecutive cases with aneurysmal SAH treated at our institution between 01/2003 and 06/2016 were eligible for this study. Different admission variables were evaluated to predict the duration of ICP increase >20 mmHg in univariate and multivariate analyses. The association of the ICP course with SAH outcome parameters (risk of cerebral infarction, in-hospital mortality, and unfavorable outcome at 6 months defined as modified Rankin scale >3) was adjusted for major outcome-relevant confounders.</p><p><strong>Results: </strong>Of 820 SAH patients, 378 individuals (46.1%) developed at least one ICP increase requiring conservative and/or surgical management after aneurysm treatment (mean duration: 1.76 days, range: 1 - 14 days). In the multivariable linear regression analysis, patients' age (unstandardized coefficient [UC]=-0.02, p <0.0001), World Federation of Neurosurgical Societies (WFNS) grade 4-5 at admission (UC=0.71, p <0.004), regular medication with the angiotensinconverting enzyme (ACE) inhibitors (UC=-0.61, p =0.01), and presence of intracerebral hemorrhage (UC=0.59, p =0.002) were associated with the duration of ICP increase. In turn, patients with longer ICP elevations were at higher risk for cerebral infarction (adjusted odds ratio [aOR]=1.32 per-day-increase, p <0.0001), in-hospital mortality (aOR=1.30, p <0.0001) and unfavorable outcome (aOR=1.43, p <0.0001). SAH patients who underwent primary decompressive craniectomy (DC) showed shorter periods of ICP increase than patients with a secondary decompression (mean: 2.8 vs 4.9 days, p <0.0001).</p><p><strong>Conclusion: </strong>The duration of ICP increase after aneurysm rupture is a strong outcome predictor and is related to younger age and higher initial severity of SAH. Further analysis of the factors impacting the course of ICP after SAH is essential for the optimization of ICP management and outcome improvement.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"253-262"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0115672026316069240502120918
Qinqin Dai, Mengmeng Zhang, Yuanli Guo, Qilan Tang, Aixia Wang, Yuming Xu, Kai Liu
The key to treating Acute Ischemic Stroke (AIS) is to rapidly reopen occluded blood vessels, restore blood flow, and rescue the ischemic penumbra. Treatment methods mainly include thrombolysis, endovascular intervention, etc. However, these treatments are limited by strict time windows and technical conditions. Simpler and more feasible methods to improve cerebral blood flow are currently a hot topic in clinical research. In recent years, several studies have shown that changes in body position can effectively improve cerebral blood flow in patients. However, the effect on the neurological functional prognosis of AIS remains inconclusive. This review has examined the effects of changes in body position on the clinical prognosis of AIS, combining relevant guidelines and the latest research. The study has provided evidence of an improvement in the clinical prognosis of AIS.
{"title":"A Study on the Effects of Different Positions on the Clinical Prognosis of Patients with Acute Ischemic Stroke.","authors":"Qinqin Dai, Mengmeng Zhang, Yuanli Guo, Qilan Tang, Aixia Wang, Yuming Xu, Kai Liu","doi":"10.2174/0115672026316069240502120918","DOIUrl":"10.2174/0115672026316069240502120918","url":null,"abstract":"<p><p>The key to treating Acute Ischemic Stroke (AIS) is to rapidly reopen occluded blood vessels, restore blood flow, and rescue the ischemic penumbra. Treatment methods mainly include thrombolysis, endovascular intervention, etc. However, these treatments are limited by strict time windows and technical conditions. Simpler and more feasible methods to improve cerebral blood flow are currently a hot topic in clinical research. In recent years, several studies have shown that changes in body position can effectively improve cerebral blood flow in patients. However, the effect on the neurological functional prognosis of AIS remains inconclusive. This review has examined the effects of changes in body position on the clinical prognosis of AIS, combining relevant guidelines and the latest research. The study has provided evidence of an improvement in the clinical prognosis of AIS.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"337-342"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}