Pub Date : 2024-10-22DOI: 10.2174/0115672026348875241011100717
Yuan Kan, Lu Yang, Changhong Ren, Chuanhui Li, Jiali Xu, Wenting Guo, Wenbo Zhao, Xunming Ji
Objective: To explore the effect of baseline Systemic Inflammatory Response reflected by platelet-to-lymphocyte ratio (PLR) and pre-thrombectomy cerebral edema reflected by Net Water Uptake (NWU) on futile recanalization in patients with Acute Ischemic Stroke (AIS) after successful thrombectomy, and to investigate the potential mediating role of baseline cerebral edema.
Methods: 134 Patients with anterior circulation ischemic stroke receiving successful thrombectomy were retrospectively studied. Their demographic and clinical characteristics were collected at admission, and the NWU was quantitatively calculated based on baseline computed tomography (CT). The predictive value of PLR for futile recanalization and the relationship between PLR, NWU, and futile recanalization using mediation analysis were explored. Patients were followed up for 90 days and were divided into a futile recanalization group and a favorable prognosis group [90-day modified Rankin Scale score of 0-2].
Results: High baseline PLR, NWU, no first-pass reperfusion, and large baseline ischemic core volume were independent predictors of futile recanalization after successful thrombectomy in patients with AIS. Mediation analysis results indicate that PLR may partially mediate the occurrence of futile recanalization through NWU.
Conclusion: Baseline PLR and NWU were independent predictors of futile recanalization, and higher PLR and NWU values were associated with a higher likelihood of futile recanalization. The findings suggest that early cerebral edema reflected by a high NWU value may be a mediator of PLR-affecting prognosis.
{"title":"The Effect of Systemic Inflammatory Response on Mechanical Thrombectomy is Partly Mediated by Pre-thrombectomy Cerebral Edema in Acute Stroke Patients.","authors":"Yuan Kan, Lu Yang, Changhong Ren, Chuanhui Li, Jiali Xu, Wenting Guo, Wenbo Zhao, Xunming Ji","doi":"10.2174/0115672026348875241011100717","DOIUrl":"https://doi.org/10.2174/0115672026348875241011100717","url":null,"abstract":"<p><strong>Objective: </strong>To explore the effect of baseline Systemic Inflammatory Response reflected by platelet-to-lymphocyte ratio (PLR) and pre-thrombectomy cerebral edema reflected by Net Water Uptake (NWU) on futile recanalization in patients with Acute Ischemic Stroke (AIS) after successful thrombectomy, and to investigate the potential mediating role of baseline cerebral edema.</p><p><strong>Methods: </strong>134 Patients with anterior circulation ischemic stroke receiving successful thrombectomy were retrospectively studied. Their demographic and clinical characteristics were collected at admission, and the NWU was quantitatively calculated based on baseline computed tomography (CT). The predictive value of PLR for futile recanalization and the relationship between PLR, NWU, and futile recanalization using mediation analysis were explored. Patients were followed up for 90 days and were divided into a futile recanalization group and a favorable prognosis group [90-day modified Rankin Scale score of 0-2].</p><p><strong>Results: </strong>High baseline PLR, NWU, no first-pass reperfusion, and large baseline ischemic core volume were independent predictors of futile recanalization after successful thrombectomy in patients with AIS. Mediation analysis results indicate that PLR may partially mediate the occurrence of futile recanalization through NWU.</p><p><strong>Conclusion: </strong>Baseline PLR and NWU were independent predictors of futile recanalization, and higher PLR and NWU values were associated with a higher likelihood of futile recanalization. The findings suggest that early cerebral edema reflected by a high NWU value may be a mediator of PLR-affecting prognosis.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515173","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}
The close connection between the brain microvascular endothelial cells (BMECs) that are enclosed within this barrier is the result of an intracellular junction, which is responsible for the constricted connection. The regulation and control of drug delivery systems both require nanoparticles, which are extremely small particles made up of a variety of materials, including polymers, metals, and other chemicals. Nanoparticles are a crucial component of the regulation and control of drug delivery systems. There is a possibility that nanomaterials composed of inorganic chemicals, such as gold nanoparticles, could be utilized in the treatment of neurodegenerative illnesses like Parkinson's disease. In addition to this, they are used as nano-carriers for the aim of distributing drugs to the region of the brain that is being targeted. There are a number of advantages that are easily apparent when compared to other methods of administering drugs for neurological diseases. The current review demonstrates both the advantages and disadvantages of utilizing a wide variety of nanomaterials for brain delivery, as well as the potential impact that this will have in the future on the safety and effectiveness of patient care.
{"title":"Nanotechnology in Drug Delivery: An Overview of Developing the Blood Brain Barrier.","authors":"Rasmita Dash, Subhankar Samanta, Bikash Ranjan Jena, Soumyaranjan Pradhan","doi":"10.2174/0115672026346307240919112023","DOIUrl":"https://doi.org/10.2174/0115672026346307240919112023","url":null,"abstract":"<p><p>The close connection between the brain microvascular endothelial cells (BMECs) that are enclosed within this barrier is the result of an intracellular junction, which is responsible for the constricted connection. The regulation and control of drug delivery systems both require nanoparticles, which are extremely small particles made up of a variety of materials, including polymers, metals, and other chemicals. Nanoparticles are a crucial component of the regulation and control of drug delivery systems. There is a possibility that nanomaterials composed of inorganic chemicals, such as gold nanoparticles, could be utilized in the treatment of neurodegenerative illnesses like Parkinson's disease. In addition to this, they are used as nano-carriers for the aim of distributing drugs to the region of the brain that is being targeted. There are a number of advantages that are easily apparent when compared to other methods of administering drugs for neurological diseases. The current review demonstrates both the advantages and disadvantages of utilizing a wide variety of nanomaterials for brain delivery, as well as the potential impact that this will have in the future on the safety and effectiveness of patient care.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483989","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 : 2024-10-11DOI: 10.2174/0115672026348862241003042336
Xie Wang, Hong Chen, Nan Shao, Xiaoyan Zhang, Chenye Huang, Xiangjun Li, Juan Zhang, Ze Chang, Le Tang, Daojun Xie
Background: Aloe-emodin (AE), a monomer derived from traditional Chinese medicine, has demonstrated remarkable efficacy in the clinical management of cognitive disorders. Ferroptosis (FPT), a specialized form of programmed cell death, plays a critical role in the pathological progression of various cognitive diseases.
Methods: This study explored the therapeutic potential of AE in a rat model of Wilson's disease cognitive impairments (WDCI) and examined whether these effects are mediated through the silencing information regulator 1 (SIRT1)-regulated FPT signaling pathway. Employing techniques, such as the Morris water maze (MWM), Hematoxylin & eosin (H&E) staining, Transmission electron microscopy (TEM), Immunofluorescence (IF), assessments of oxidative stress markers, and measurements of FPT-related protein levels, we evaluated the extent of SIRT1-mediated FPT and the therapeutic efficacy of AE.
Results: The findings from the WD copper-loaded rat model experiments revealed that MWM, H&E, TEM, and IF outcomes indicated AE's potential to promote the restoration of learning and memory functions, ameliorate hippocampal neuronal morphological damage, and preserve cell membrane integrity. Results from western blot (WB) and ELISA analyses demonstrated that AE markedly upregulated the expression of SIRT1, nuclear factor erythroid-2-related factor 2 (Nrf2), solute carrier family 7 member 11 (SCL7A11), and glutathione peroxidase 4 (GPX4) proteins while simultaneously reversing the expression of oxidative stress markers such as malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD), and reactive oxygen species (ROS). Consequently, we posit that AE may attenuate WD copper-loaded rat model hippocampal neuronal FPT by activating the SIRT1-mediated signaling pathway.
Conclusion: These findings suggested that AE mitigates WD copper-loaded rat model hippocampal neuronal damage through the activation of SIRT1-mediated FPT, thereby presenting a valuable candidate Chinese herbal monomer for the clinical treatment of WDCI.
{"title":"Protective Effect of Aloe-emodin on Cognitive Function in Copper-loaded Rats Based on The Inhibition of Hippocampal Neuron Ferroptosis.","authors":"Xie Wang, Hong Chen, Nan Shao, Xiaoyan Zhang, Chenye Huang, Xiangjun Li, Juan Zhang, Ze Chang, Le Tang, Daojun Xie","doi":"10.2174/0115672026348862241003042336","DOIUrl":"https://doi.org/10.2174/0115672026348862241003042336","url":null,"abstract":"<p><strong>Background: </strong>Aloe-emodin (AE), a monomer derived from traditional Chinese medicine, has demonstrated remarkable efficacy in the clinical management of cognitive disorders. Ferroptosis (FPT), a specialized form of programmed cell death, plays a critical role in the pathological progression of various cognitive diseases.</p><p><strong>Methods: </strong>This study explored the therapeutic potential of AE in a rat model of Wilson's disease cognitive impairments (WDCI) and examined whether these effects are mediated through the silencing information regulator 1 (SIRT1)-regulated FPT signaling pathway. Employing techniques, such as the Morris water maze (MWM), Hematoxylin & eosin (H&E) staining, Transmission electron microscopy (TEM), Immunofluorescence (IF), assessments of oxidative stress markers, and measurements of FPT-related protein levels, we evaluated the extent of SIRT1-mediated FPT and the therapeutic efficacy of AE.</p><p><strong>Results: </strong>The findings from the WD copper-loaded rat model experiments revealed that MWM, H&E, TEM, and IF outcomes indicated AE's potential to promote the restoration of learning and memory functions, ameliorate hippocampal neuronal morphological damage, and preserve cell membrane integrity. Results from western blot (WB) and ELISA analyses demonstrated that AE markedly upregulated the expression of SIRT1, nuclear factor erythroid-2-related factor 2 (Nrf2), solute carrier family 7 member 11 (SCL7A11), and glutathione peroxidase 4 (GPX4) proteins while simultaneously reversing the expression of oxidative stress markers such as malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD), and reactive oxygen species (ROS). Consequently, we posit that AE may attenuate WD copper-loaded rat model hippocampal neuronal FPT by activating the SIRT1-mediated signaling pathway.</p><p><strong>Conclusion: </strong>These findings suggested that AE mitigates WD copper-loaded rat model hippocampal neuronal damage through the activation of SIRT1-mediated FPT, thereby presenting a valuable candidate Chinese herbal monomer for the clinical treatment of WDCI.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483990","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}
Objective: Nearly half of Acute Ischemic Stroke (AIS) patients failed to achieve favorable outcomes despite successful reperfusion treatment. This phenomenon is referred to as Futile Recanalization (FR). Screening patients at risk of FR is vital for stroke management. Previous studies reported the diagnostic value of alkaline phosphatase (ALP) levels in certain aspects of stroke prognosis. However, the association between serum ALP level and FR among AIS patients treated with thrombectomy remained unclear.
Methods: We screened stroke patients who underwent thrombectomy at our center from January 2017 to June 2021, and those who achieved successful reperfusion (modified Thrombolysis in Cerebral Infarction score=3) were ultimately analyzed. Demographic information, vascular risk factors, and laboratory test results were collected at admission. The 3-month unfavorable outcome was defined as a modified Rankin Scale score of 3 to 6. The effect of ALP levels on FR was investigated with a logistic regression model.
Results: Of 788 patients who underwent thrombectomy, 277 achieved successful reperfusion. Among them, 142 patients (51.3%) failed to realize favorable outcomes at 3 months. After adjusting for confounding variables, higher ALP levels (p =0.002) at admission were independently associated with unfavorable outcomes at three months. Adding ALP values to conventional risk factors improved the performance of prediction models for FR.
Conclusion: The current study found that the serum ALP levels at admission emerged as a potential biomarker for futile reperfusion in stroke patients undergoing thrombectomy. Further studies are warranted to confirm the clinical applicability of ALP level for futile recanalization prediction.
目的:近一半的急性缺血性脑卒中(AIS)患者尽管接受了成功的再灌注治疗,但仍无法获得良好的预后。这种现象被称为徒劳再灌注(FR)。筛查有 FR 风险的患者对卒中治疗至关重要。之前的研究报道了碱性磷酸酶(ALP)水平对卒中预后某些方面的诊断价值。然而,在接受血栓切除术治疗的 AIS 患者中,血清 ALP 水平与 FR 之间的关系仍不明确:我们筛选了 2017 年 1 月至 2021 年 6 月在本中心接受血栓切除术的脑卒中患者,最终分析了成功再灌注(改良脑梗死溶栓评分=3)的患者。入院时收集了人口统计学信息、血管风险因素和实验室检查结果。3个月的不良预后定义为改良Rankin量表评分3至6分。通过逻辑回归模型研究了ALP水平对FR的影响:结果:在接受血栓切除术的 788 例患者中,277 例成功实现了再灌注。其中,142 名患者(51.3%)在 3 个月后未能获得良好的治疗效果。在对混杂变量进行调整后,入院时较高的 ALP 水平(p =0.002)与三个月后的不良预后独立相关。在常规风险因素中加入 ALP 值可提高 FR 预测模型的性能:本研究发现,入院时的血清 ALP 水平是接受血栓切除术的卒中患者进行无效再灌注的潜在生物标志物。为了证实 ALP 水平对无效再灌注预测的临床适用性,还需要进一步研究。
{"title":"Association of Alkaline Phosphatase Level with Futile Recanalization in Acute Ischemic Stroke Patients Treated with Endovascular Thrombectomy.","authors":"Milan Jia, Wantong Yu, Feiyang Jin, Jiali Xu, Wenting Guo, Mengke Zhang, Sijie Li, Changhong Ren, Yuchuan Ding, Wenbo Zhao, Jing Lan, Xunming Ji","doi":"10.2174/0115672026344020240911114809","DOIUrl":"https://doi.org/10.2174/0115672026344020240911114809","url":null,"abstract":"<p><strong>Objective: </strong>Nearly half of Acute Ischemic Stroke (AIS) patients failed to achieve favorable outcomes despite successful reperfusion treatment. This phenomenon is referred to as Futile Recanalization (FR). Screening patients at risk of FR is vital for stroke management. Previous studies reported the diagnostic value of alkaline phosphatase (ALP) levels in certain aspects of stroke prognosis. However, the association between serum ALP level and FR among AIS patients treated with thrombectomy remained unclear.</p><p><strong>Methods: </strong>We screened stroke patients who underwent thrombectomy at our center from January 2017 to June 2021, and those who achieved successful reperfusion (modified Thrombolysis in Cerebral Infarction score=3) were ultimately analyzed. Demographic information, vascular risk factors, and laboratory test results were collected at admission. The 3-month unfavorable outcome was defined as a modified Rankin Scale score of 3 to 6. The effect of ALP levels on FR was investigated with a logistic regression model.</p><p><strong>Results: </strong>Of 788 patients who underwent thrombectomy, 277 achieved successful reperfusion. Among them, 142 patients (51.3%) failed to realize favorable outcomes at 3 months. After adjusting for confounding variables, higher ALP levels (p =0.002) at admission were independently associated with unfavorable outcomes at three months. Adding ALP values to conventional risk factors improved the performance of prediction models for FR.</p><p><strong>Conclusion: </strong>The current study found that the serum ALP levels at admission emerged as a potential biomarker for futile reperfusion in stroke patients undergoing thrombectomy. Further studies are warranted to confirm the clinical applicability of ALP level for futile recanalization prediction.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373874","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 : 2024-09-12DOI: 10.2174/0115672026346635240816095721
Meng Ke Zhang, Xian Wang, Xi Chen, Jiali Xu, Wenting Guo, Chang Hong Ren, Sijie Li, Wen Bo Zhao, Chuanjie Wu, Xunming Ji
Background: Increasing evidence of circadian biology may influence the physiopathologic mechanism, progression, and recovery of stroke. However, few data have shown about circadian rhythm on futile recanalization (FR) in patients treated with endovascular treatment (EVT).
Methods: From 2017 to 2021, an observational cohort of acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) underwent EVT was conducted. FR was defined as the failure to achieve functional independence in patients at 90 days after EVT, although the occluded vessels reached a recanalization. The effect of circadian rhythm on FR was investigated using the logistic regression model.
Results: Of 783 patients, there were 149 patients who had stroke onset between 23:00-6:59, 318 patients between 7:00-14:59, and 316 patients between 15:00-22:59. Patients suffered a stroke during 15:00-22:59 had shorter OTP (p =0.001) time, shorter OTR (p<0.001) time, higher rate of intravenous thrombolysis (p =0.001) than groups of other time intervals. The rate of FR post-EVT in patients who had a stroke between 15:00-22:59 was significantly higher than in those with stroke onset between 23:00-6:59 (p =0.017). After adjusting for confounding factors, the time of stroke occurring during 15:00-22:59 (adjusted OR [aOR], 1.652; 95%CI, 1.024-2.666, p =0.04) was an independent predictor of FR.
Conclusion: Circadian rhythm can directly or indirectly affect the occurrence, development, and prognosis of AIS. More studies may be needed in the future to validate the results of our study and to explore the potential mechanisms behind the effects of circadian rhythms on FR.
{"title":"Role of Circadian Rhythm Changes on Functional Dependence Despite Successful Repercussion in Patients with Endovascular Treatment.","authors":"Meng Ke Zhang, Xian Wang, Xi Chen, Jiali Xu, Wenting Guo, Chang Hong Ren, Sijie Li, Wen Bo Zhao, Chuanjie Wu, Xunming Ji","doi":"10.2174/0115672026346635240816095721","DOIUrl":"https://doi.org/10.2174/0115672026346635240816095721","url":null,"abstract":"<p><strong>Background: </strong>Increasing evidence of circadian biology may influence the physiopathologic mechanism, progression, and recovery of stroke. However, few data have shown about circadian rhythm on futile recanalization (FR) in patients treated with endovascular treatment (EVT).</p><p><strong>Methods: </strong>From 2017 to 2021, an observational cohort of acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) underwent EVT was conducted. FR was defined as the failure to achieve functional independence in patients at 90 days after EVT, although the occluded vessels reached a recanalization. The effect of circadian rhythm on FR was investigated using the logistic regression model.</p><p><strong>Results: </strong>Of 783 patients, there were 149 patients who had stroke onset between 23:00-6:59, 318 patients between 7:00-14:59, and 316 patients between 15:00-22:59. Patients suffered a stroke during 15:00-22:59 had shorter OTP (p =0.001) time, shorter OTR (p<0.001) time, higher rate of intravenous thrombolysis (p =0.001) than groups of other time intervals. The rate of FR post-EVT in patients who had a stroke between 15:00-22:59 was significantly higher than in those with stroke onset between 23:00-6:59 (p =0.017). After adjusting for confounding factors, the time of stroke occurring during 15:00-22:59 (adjusted OR [aOR], 1.652; 95%CI, 1.024-2.666, p =0.04) was an independent predictor of FR.</p><p><strong>Conclusion: </strong>Circadian rhythm can directly or indirectly affect the occurrence, development, and prognosis of AIS. More studies may be needed in the future to validate the results of our study and to explore the potential mechanisms behind the effects of circadian rhythms on FR.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142304520","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 : 2024-09-03DOI: 10.2174/0115672026349500240826100531
Aanchal Verma, Ahsas Goyal
Background: Parkinson's disease is an illness marked by a gradual mitigation of dopamine neurons within the substantia nigra, which eventually leads to a deficiency of dopamine that further gives rise to mobility as well as cognitive impairments. Through long-established traditions, a wide array of Traditional Chinese Medicines (TCM) have undergone testing and are employed to avoid neurodegenerative disorders. Plumbagin is the primary active component of a medication called Baihua Dan or Plumbago zeylanica L., which is clinically used in China.
Objectives: This study investigated plumbagin-induced alterations in a Parkinson's disease rat model instigated by subcutaneous rotenone injection.
Methods: Male rats were administered subcutaneous injections of rotenone at a dosage of 1.5 mg/kg, followed by the treatment with varying doses of plumbagin (10, 20, and 40 mg/kg) through the oral route. The rats underwent various motor ability tests, including the actophotometer, rotarod, open field, beam walk, gait evaluation, ability to grip, and catalepsy bar tests. Furthermore, the brain dopamine level was then estimated for the extracted tissues. Also, through molecular docking, the binding effectiveness of plumbagin was assessed for human MAO-B. After that, plumbagin was put through 100 ns of molecular dynamic simulations to examine the stability of its conformational binding to the target protein. Furthermore, ADMET tests were used to verify Plumbagin's druggability.
Results: Plumbagin was found to alleviate rotenone-induced motor abnormalities and restore brain dopamine levels. Furthermore, plumbagin showed excellent interactions with MAO-B (monoamine oxidase-B) when compared with selegiline (a standard drug for Parkinson's disease).
Conclusion: These findings underscore the potential therapeutic efficacy of plumbagin in mitigating behavioural deficits in rotenone-induced rodents. Considering this, plumbagin might be a feasible pharmacological strategy for the control of rotenone-triggered behavioural impairment in rats (in vivo), and it might display interesting interactions with MAO-B (in silico).
{"title":"Plumbagin's Healing Effect on Motor Impairment in Rotenone-toxified Rodents.","authors":"Aanchal Verma, Ahsas Goyal","doi":"10.2174/0115672026349500240826100531","DOIUrl":"https://doi.org/10.2174/0115672026349500240826100531","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease is an illness marked by a gradual mitigation of dopamine neurons within the substantia nigra, which eventually leads to a deficiency of dopamine that further gives rise to mobility as well as cognitive impairments. Through long-established traditions, a wide array of Traditional Chinese Medicines (TCM) have undergone testing and are employed to avoid neurodegenerative disorders. Plumbagin is the primary active component of a medication called Baihua Dan or Plumbago zeylanica L., which is clinically used in China.</p><p><strong>Objectives: </strong>This study investigated plumbagin-induced alterations in a Parkinson's disease rat model instigated by subcutaneous rotenone injection.</p><p><strong>Methods: </strong>Male rats were administered subcutaneous injections of rotenone at a dosage of 1.5 mg/kg, followed by the treatment with varying doses of plumbagin (10, 20, and 40 mg/kg) through the oral route. The rats underwent various motor ability tests, including the actophotometer, rotarod, open field, beam walk, gait evaluation, ability to grip, and catalepsy bar tests. Furthermore, the brain dopamine level was then estimated for the extracted tissues. Also, through molecular docking, the binding effectiveness of plumbagin was assessed for human MAO-B. After that, plumbagin was put through 100 ns of molecular dynamic simulations to examine the stability of its conformational binding to the target protein. Furthermore, ADMET tests were used to verify Plumbagin's druggability.</p><p><strong>Results: </strong>Plumbagin was found to alleviate rotenone-induced motor abnormalities and restore brain dopamine levels. Furthermore, plumbagin showed excellent interactions with MAO-B (monoamine oxidase-B) when compared with selegiline (a standard drug for Parkinson's disease).</p><p><strong>Conclusion: </strong>These findings underscore the potential therapeutic efficacy of plumbagin in mitigating behavioural deficits in rotenone-induced rodents. Considering this, plumbagin might be a feasible pharmacological strategy for the control of rotenone-triggered behavioural impairment in rats (in vivo), and it might display interesting interactions with MAO-B (in silico).</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127729","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 : 2024-08-30DOI: 10.2174/0115672026336440240822063430
Tarun Sharma, Sidharth Mehan, Aarti Tiwari, Zuber Khan, Ghanshyam Das Gupta, Acharan S Narula
Multiple sclerosis [MS] is a progressive autoimmune condition that primarily affects young people and is characterized by demyelination and neurodegeneration of the central nervous system [CNS]. This in-depth review explores the complex involvement of oligodendrocytes, the primary myelin- producing cells in the CNS, in the pathophysiology of MS. It discusses the biochemical processes and signalling pathways required for oligodendrocytes to function and remain alive, as well as how they might fail and cause demyelination to occur. We investigate developing therapeutic options that target remyelination, a fundamental component of MS treatment. Remyelination approaches promote the survival and differentiation of oligodendrocyte precursor cells [OPCs], restoring myelin sheaths. This improves nerve fibre function and may prevent MS from worsening. We examine crucial parameters influencing remyelination success, such as OPC density, ageing, and signalling pathway regulation [e.g., Retinoid X receptor, LINGO-1, Notch]. The review also examines existing neuroprotective and antiinflammatory medications being studied to see if they can assist oligodendrocytes in surviving and reducing the severity of MS symptoms. The review focuses on medicines that target the myelin metabolism in oligodendrocytes. Altering oligodendrocyte metabolism has been linked to reversing demyelination and improving MS patient outcomes through various mechanisms. We also explore potential breakthroughs, including innovative antisense technologies, deep brain stimulation, and the impact of gut health and exercise on MS development. The article discusses the possibility of personalized medicine in MS therapy, emphasizing the importance of specific medicines based on individual molecular profiles. The study emphasizes the need for reliable biomarkers and improved imaging tools for monitoring disease progression and therapy response. Finally, this review focuses on the importance of oligodendrocytes in MS and the potential for remyelination therapy. It also underlines the importance of continued research to develop more effective treatment regimens, taking into account the complexities of MS pathology and the different factors that influence disease progression and treatment.
多发性硬化症(MS)是一种主要影响年轻人的进行性自身免疫性疾病,以中枢神经系统(CNS)的脱髓鞘和神经变性为特征。这篇深度综述探讨了中枢神经系统中主要的髓鞘生成细胞--少突胶质细胞在多发性硬化症病理生理学中的复杂参与。它讨论了少突胶质细胞发挥功能和保持活力所需的生化过程和信号通路,以及它们如何可能失效并导致脱髓鞘的发生。我们研究了针对多发性硬化症治疗的基本组成部分--再髓鞘化的治疗方案。再髓鞘化方法可促进少突胶质前体细胞(OPCs)的存活和分化,恢复髓鞘。这能改善神经纤维功能,防止多发性硬化症恶化。我们研究了影响再髓鞘化成功与否的关键参数,如 OPC 密度、老化和信号通路调控(如视黄醇 X 受体、LINGO-1、Notch)。综述还探讨了正在研究的现有神经保护和抗炎药物,以了解这些药物能否帮助少突胶质细胞存活并减轻多发性硬化症症状的严重程度。综述的重点是针对少突胶质细胞髓鞘代谢的药物。改变少突胶质细胞的新陈代谢与逆转脱髓鞘和通过各种机制改善多发性硬化症患者的预后有关。我们还探讨了潜在的突破,包括创新的反义技术、脑深部刺激以及肠道健康和运动对多发性硬化症发展的影响。文章讨论了多发性硬化症治疗中个性化药物的可能性,强调了基于个体分子特征的特定药物的重要性。研究强调需要可靠的生物标志物和改进的成像工具来监测疾病进展和治疗反应。最后,本综述重点讨论了少突胶质细胞在多发性硬化症中的重要性以及再髓鞘化疗法的潜力。它还强调了继续研究开发更有效治疗方案的重要性,同时考虑到多发性硬化症病理的复杂性以及影响疾病进展和治疗的不同因素。
{"title":"Targeting Oligodendrocyte Dynamics and Remyelination: Emerging Therapies and Personalized Approaches in Multiple Sclerosis Management.","authors":"Tarun Sharma, Sidharth Mehan, Aarti Tiwari, Zuber Khan, Ghanshyam Das Gupta, Acharan S Narula","doi":"10.2174/0115672026336440240822063430","DOIUrl":"https://doi.org/10.2174/0115672026336440240822063430","url":null,"abstract":"<p><p>Multiple sclerosis [MS] is a progressive autoimmune condition that primarily affects young people and is characterized by demyelination and neurodegeneration of the central nervous system [CNS]. This in-depth review explores the complex involvement of oligodendrocytes, the primary myelin- producing cells in the CNS, in the pathophysiology of MS. It discusses the biochemical processes and signalling pathways required for oligodendrocytes to function and remain alive, as well as how they might fail and cause demyelination to occur. We investigate developing therapeutic options that target remyelination, a fundamental component of MS treatment. Remyelination approaches promote the survival and differentiation of oligodendrocyte precursor cells [OPCs], restoring myelin sheaths. This improves nerve fibre function and may prevent MS from worsening. We examine crucial parameters influencing remyelination success, such as OPC density, ageing, and signalling pathway regulation [e.g., Retinoid X receptor, LINGO-1, Notch]. The review also examines existing neuroprotective and antiinflammatory medications being studied to see if they can assist oligodendrocytes in surviving and reducing the severity of MS symptoms. The review focuses on medicines that target the myelin metabolism in oligodendrocytes. Altering oligodendrocyte metabolism has been linked to reversing demyelination and improving MS patient outcomes through various mechanisms. We also explore potential breakthroughs, including innovative antisense technologies, deep brain stimulation, and the impact of gut health and exercise on MS development. The article discusses the possibility of personalized medicine in MS therapy, emphasizing the importance of specific medicines based on individual molecular profiles. The study emphasizes the need for reliable biomarkers and improved imaging tools for monitoring disease progression and therapy response. Finally, this review focuses on the importance of oligodendrocytes in MS and the potential for remyelination therapy. It also underlines the importance of continued research to develop more effective treatment regimens, taking into account the complexities of MS pathology and the different factors that influence disease progression and treatment.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116419","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 : 2024-06-20DOI: 10.2174/0115672026309198240605102300
Yu Huang, Chuyue Wu, Cuiping Du, Da Lei, Li Li, Shengli Chen
Background: Mechanical thrombectomy (MT) is usually recommended for acute ischemic stroke (AIS) due to large vessel occlusion (LVO) within the time window (6 hours after the disease onset). However, poor prognosis in acute great vascular occlusive stroke after MT, which is not an uncommon occurrence, can be attributed to an absence of appropriate postoperative monitoring. Transcranial Doppler (TCD) ultrasound and quantitative electroencephalography (QEEG) offer the advantages of fast, convenient, and bedside examinations compared with conventional imaging techniques.
Objective: We aimed to analyze the predictive performance of clinical factors, Transcranial Doppler (TCD) ultrasound and quantitative electroencephalography (QEEG) for the prognosis of patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) at 90 days after discharge.
Method: Patients achieved revascularization through MT performed within 6 hours after the onset of AIS due to LVO were included. We use the data to build four predictive models of prognosis and compared the predictive performance measured by the area under the curve, sensitivity, and specificity.
Result: A total of 74 patients were included in the study. Among them, 47 patients had a poor prognosis (63.5%) on discharge, and 45 patients had a poor prognosis (60.8%) at 90 days after discharge. Independent predictors of poor prognosis at 90 days after discharge were identified as follows: age, NIHSS score on admission, PI on the affected/healthy side, and RAP. Among the four models built, AUC was the highest (reaching 0.831) when age was combined with NIHSS score on admission, TCD parameters (VD on the affected side, PI on the affected/healthy side), and QEEG parameter (RAP) for prognostic prediction. However, AUC of the four predictive models did not differ significantly (P>0.05).
Conclusion: Age, NIHSS score on admission, TCD parameters, and QEEG parameter were independent predictors of the prognosis at 90 days after discharge in patients receiving MT for AIS due to LVO in the anterior circulation. The model combining the above four parameters may be helpful for prognostic prediction in such patients.
{"title":"A Clinical Model predicting the 90-Day Prognosis after Mechanical Thrombectomy in Patients with Acute Ischemic Stroke: A Retrospective Study.","authors":"Yu Huang, Chuyue Wu, Cuiping Du, Da Lei, Li Li, Shengli Chen","doi":"10.2174/0115672026309198240605102300","DOIUrl":"https://doi.org/10.2174/0115672026309198240605102300","url":null,"abstract":"<p><strong>Background: </strong>Mechanical thrombectomy (MT) is usually recommended for acute ischemic stroke (AIS) due to large vessel occlusion (LVO) within the time window (6 hours after the disease onset). However, poor prognosis in acute great vascular occlusive stroke after MT, which is not an uncommon occurrence, can be attributed to an absence of appropriate postoperative monitoring. Transcranial Doppler (TCD) ultrasound and quantitative electroencephalography (QEEG) offer the advantages of fast, convenient, and bedside examinations compared with conventional imaging techniques.</p><p><strong>Objective: </strong>We aimed to analyze the predictive performance of clinical factors, Transcranial Doppler (TCD) ultrasound and quantitative electroencephalography (QEEG) for the prognosis of patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) at 90 days after discharge.</p><p><strong>Method: </strong>Patients achieved revascularization through MT performed within 6 hours after the onset of AIS due to LVO were included. We use the data to build four predictive models of prognosis and compared the predictive performance measured by the area under the curve, sensitivity, and specificity.</p><p><strong>Result: </strong>A total of 74 patients were included in the study. Among them, 47 patients had a poor prognosis (63.5%) on discharge, and 45 patients had a poor prognosis (60.8%) at 90 days after discharge. Independent predictors of poor prognosis at 90 days after discharge were identified as follows: age, NIHSS score on admission, PI on the affected/healthy side, and RAP. Among the four models built, AUC was the highest (reaching 0.831) when age was combined with NIHSS score on admission, TCD parameters (VD on the affected side, PI on the affected/healthy side), and QEEG parameter (RAP) for prognostic prediction. However, AUC of the four predictive models did not differ significantly (P>0.05).</p><p><strong>Conclusion: </strong>Age, NIHSS score on admission, TCD parameters, and QEEG parameter were independent predictors of the prognosis at 90 days after discharge in patients receiving MT for AIS due to LVO in the anterior circulation. The model combining the above four parameters may be helpful for prognostic prediction in such patients.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443966","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 : 2024-05-15DOI: 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":"https://doi.org/10.2174/0115672026316069240502120918","url":null,"abstract":"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.","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":"84 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140973549","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}