Current neurovascular research最新文献

{"title":"Neutrophil-to-albumin Ratio as a Prognostic Factor in Patients with Acute Ischemic Stroke.","authors":"Jiajia Bao, Yang Zhang, Mengmeng Ma, Jian Wang, Xin Jiang, Jian Guo, Li He","doi":"10.2174/0115672026328594240614080241","DOIUrl":"10.2174/0115672026328594240614080241","url":null,"abstract":"<p><strong>Background: </strong>Neutrophil-To-Albumin Ratio (NAR) is a novel inflammatory biomarker. However, the potential prognostic value of NAR in acute ischemic stroke (AIS) remains unclear. This study aimed to evaluate whether NAR levels correlated with the 3-month modified Rankin scale (mRS) in patients with AIS.</p><p><strong>Methods: </strong>AIS patients were included in this retrospective study. NAR was calculated as the ratio of absolute neutrophil count to serum albumin level. Logistic regression analyses were used to investigate the effect of NAR on 3-month mRS of AIS. The predictive values of NAR, albumin level, and neutrophil count were compared utilizing receiver operating characteristic (ROC) curves. Moreover, subgroup analyses and interaction tests were conducted to evaluate the consistency of NAR's effect on AIS prognosis.</p><p><strong>Results: </strong>Of the 780 patients included, 403 (51.67%) had a poor clinical outcome (mRS 3-6) at 3 months. NAR was independently correlated to 3-month poor functional outcome after adjusting for confounders (Odds ratios (OR), 9.34; 95% confidence intervals (CI), 1.09 to 80.13; p =0.0417). Subgroup analysis showed a relative effect consistent with the overall population results, and no statistical interactions were found in the subgroups (all p for interaction > 0.05). The ROC curve showed that the prognosis-related cutoff value for NAR was 0.123, with corresponding specificity and sensitivity of 53.55% and 63.94%, respectively. When comparing the predictive power, NAR (0.590; 95%CI 0.549-0.630) exhibited the highest area under the curve (AUC) of ROC compared to neutrophils (0.584; 95%CI 0.543-0.624) and albumin (0.540; 95%CI 0.500-0.581).</p><p><strong>Conclusion: </strong>There is a positive relationship between NAR levels and 3-month poor functional outcomes in AIS patients, supporting the potential of NAR as a readily available and economic serum biomarker for the early identification of AIS prognosis. Further studies are required to validate the prognostic value and clinical utility of the NAR.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141452527","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}

{"title":"Association between Interleukin-6 and Multiple Acute Infarctions in Symptomatic Intracranial Atherosclerotic Disease.","authors":"Jinglin Mo, Zimo Chen, Mengxing Wang, Aichun Cheng, Jiejie Li, Yuesong Pan, Yong Jiang, Jing Jing, Yongjun Wang, Yuehua Pu, Zixiao Li","doi":"10.2174/0115672026323216240722194958","DOIUrl":"10.2174/0115672026323216240722194958","url":null,"abstract":"<p><strong>Background: </strong>Interleukin-6 (IL-6) plays an important role in the pathophysiology of atherosclerosis. This study aimed to determine whether IL-6 is a crucial biomarker associated with Multiple Acute Infarctions (MAIs), which indicate an important stroke mechanism of artery-to-artery embolism with a high risk of stroke recurrence in symptomatic Intracranial Atherosclerotic Disease (sICAD). We tested the association between circulating IL-6 levels and the presence of MAIs in a prospective population-based registry.</p><p><strong>Methods: </strong>We included 1,919 patients with sICAD and baseline IL-6 levels from the Third China National Stroke Registry for the current analysis, The baseline IL-6 was centrally measured at Beijing Tiantan Hospital, Images of the brain parenchyma and vascular structures were digitized and then blindly and independently read by two groups of trained readers, The recruited patients were divided into 3 groups according to IL-6 tertiles, The relationship between baseline IL-6 tertile levels and the presence of MAIs was modeled using multivariate logistic regression.</p><p><strong>Results: </strong>Compared to patients in the first IL-6 tertile those in the second and third tertiles demonstrated a significantly higher proportion of MAIs. The odds ratios were 1.81 [95% Confidence Interval (CI), 1.42-2.30] for the second versus first tertile and 2.15 (95% CI 1.66-2.79) for the third versus first tertile, The proportion of patients with MAIs increased with rising IL-6 tertiles observed at 59.3%, 71.6% and 76.4% for the first, second and third tertiles, respectively (P for trend < 0.001). The association between higher IL-6 tertiles and increased proportion of MAIs was also present in subgroups defined by age < 65 years, age ≥ 65 years, male, and high-sensitivity C-reactive Protein (hs-CRP) ≥ 2 mg/L. Furthermore, a significant interaction was detected for the hs- CRP subgroup (P = 0.038). In sensitivity analyses, the positive correlation between IL-6 levels and the proportion of MAIs remained consistent.</p><p><strong>Conclusion: </strong>In patients with sICAD, higher IL-6 levels were associated with an increased proportion of MAIs. IL-6 could be used as a biomarker and a potential therapeutic target for future atherosclerosis treatment and prevention in patients with sICAD.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790591","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}

{"title":"Diffusion-weighted Imaging Detection of Acute Ischemia Brain Lesions in Spontaneous Intracerebral Hemorrhage Associated with White Matter Hyperintensities, Enlarged Perivascular Spaces and Diabetes Mellitus.","authors":"Yutong Hou, Wei Qin, Shuna Yang, Yue Li, Lei Yang, Wenli Hu","doi":"10.2174/0115672026283323240108052711","DOIUrl":"10.2174/0115672026283323240108052711","url":null,"abstract":"<p><strong>Objective: </strong>Diffusion-weighted imaging (DWI) is commonly detected after spontaneous intracerebral hemorrhage (sICH) and is associated with poor functional outcomes. However, the etiology and significance of DWI lesions remain unclear. Thus, our study aimed to explore the prevalence and risk factors of acute ischemic lesions in sICH and discussed the possible mechanisms.</p><p><strong>Methods: </strong>We conducted a retrospective review of a consecutive cohort of 408 patients from June 2013 to October 2019 with sICH, who had brain computed tomography (CT) and magnetic resonance imaging (MRI) within 14 days of symptoms onset. Acute ischemic lesions were assessed on MRI using DWI lesions. We compared the clinical and imaging characteristics of patients with and without DWI lesions. The data were analyzed by univariate and multivariate logistic regression.</p><p><strong>Results: </strong>Among the enrolled 408 patients, the mean age was 56.8 ± 14.5 years, 68 (16.7%) of them had been diagnosed with diabetes mellitus (DM). DWI lesions were observed in 89 (21.8%) patients, and most of them had a history of lacunar infarctions, which were located in cortical or subcortical. In multivariate logistic regression analysis, DM (odds ratio (OR) 3.962, p <0.001), severe deep white matter hypertensities (DWMH) (OR 2.463, p =0.001) and severe centrum semiovale enlarged perivascular spaces (CSO-EPVS) (OR 2.679, p =0.001) were independently associated with the presence of DWI lesions.</p><p><strong>Conclusion: </strong>In our cohort, we found DM, severe DWMH and severe CSO-EPVS were the independent risk factors in sICH patients with DWI lesions.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577284","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}

{"title":"Enlarged Perivascular Space in the Basal Ganglia is Associated with Cerebral Venous Reflux in Patients with Recent Small Subcortical Infarction.","authors":"Zhengrong Wu, Ke Zhang, Ce Zong, Hongbing Liu, Yanhong Wang, Yuming Xu, Yuan Gao","doi":"10.2174/0115672026299546240130092550","DOIUrl":"10.2174/0115672026299546240130092550","url":null,"abstract":"<p><strong>Background: </strong>Research has linked enlarged perivascular spaces (EPVS) to cerebral venous reflux (CVR) in patients with hypertensive intracerebral hemorrhage, but it is unclear whether this association exists in recent small subcortical infarct (RSSI) patients.</p><p><strong>Objective: </strong>This study aimed to investigate the correlation between EPVS and CVR in patients with RSSI.</p><p><strong>Method: </strong>This study included 297 patients, selected from patients with RSSI in the lenticulostriate artery admitted to the Department of Neurology of the First Affiliated Hospital of Zhengzhou University. CVR was assessed by time-of-flight magnetic resonance angiography (TOF-MRA). The relationship between EPVS and CVR was studied using multiple logistic regression analysis.</p><p><strong>Results: </strong>This study included patients with an average age of 59.84±12.27 years, including 201 males (67.7%). CVR was observed in 40 (13.5%) patients. Compared to the group without CVR, the proportions of male patients and patients with a history of smoking and drinking were higher in the CVR group. The proportions of high-grade EPVS in the centrum semiovale region [23 cases (57.5%) vs. 108 cases (42.0%), <i>p</i> =0.067] and the basal ganglia region [30 cases (75.0%) vs. 133 cases (51.8%), <i>p</i> =0.006] were higher in the CVR group. After multiple logistic regression analysis, high-grade EPVS in the basal ganglia region was still associated with CVR (OR, 2.68; 95% CI, 1.22-5.87;<i>p</i>=0.014).</p><p><strong>Conclusion: </strong>In the population with RSSI, EPVS in basal ganglia is significantly associated with CVR, suggesting a close relationship between venous dysfunction and the formation of EPVS.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139699121","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}

{"title":"Microglia: Formidable Players in Alzheimer's Disease and Other Neurodegenerative Disorders.","authors":"Kenneth Maiese","doi":"10.2174/1567202620999231027155308","DOIUrl":"10.2174/1567202620999231027155308","url":null,"abstract":"","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54232865","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}

{"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":null,"pages":null},"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}

{"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":null,"pages":null},"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}

{"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":null,"pages":null},"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}

{"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":null,"pages":null},"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}

{"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_A.</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_A 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_A 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_A receptor levels and that the inhibition of CREB expression may reduce the incidence of DRE.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":null,"pages":null},"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}