Ischemic stroke is an important disease leading to death and disability for all human beings, and the key to its treatment lies in the early opening of obstructed vessels and restoration of perfusion to the local infa...Ischemic stroke is an important disease leading to death and disability for all human beings, and the key to its treatment lies in the early opening of obstructed vessels and restoration of perfusion to the local infarcted area. Intravenous thrombolysis with tissue plasminogen activator (tPA) is one of the effective therapies to achieve revascularization, but it faces strict indications with a narrow therapeutic time window, and significantly increases the incidence of hemorrhagic transformation, HT, after reperfusion of the infarcted foci, which greatly reduces the incidence of patients with ischemic stroke. which significantly increases the incidence of hemorrhagic transformation (HT) after reperfusion of the infarcted focus, greatly reducing patient utilization and clinical benefit. Since the mechanism of HT has not been fully elucidated, and the related molecular mechanisms are complex and interactive, there is no specific and effective therapy to avoid the occurrence of HT. In this article, we focus on the research progress on the mechanism of HT after tPA intravenous thrombolysis in ischemic stroke patients from the aspects of vascular integrity disruption, oxidative stress, and neuroinflammatory response and the corresponding therapeutic strategies, in order to improve the safety and prognosis of tPA intravenous thrombolysis in the clinic.展开更多
BACKGROUND： Nitric oxide synthase （NOS） inhibrtors have been widely used to investigate the role of NO on cerebral ischemic injury, but the results are controversial. Moreover, it has been considered to aggravate t...BACKGROUND： Nitric oxide synthase （NOS） inhibrtors have been widely used to investigate the role of NO on cerebral ischemic injury, but the results are controversial. Moreover, it has been considered to aggravate the ischemic neuronal damage with the release of excessively excitatory amino acids （EAA） during cerebral ischemia. On the other hand, some inhibitory amino acid is suggested to be important for the neuronal protection against ischemic brain damage. Our study has recently showed that treatment with the NOS inhibitor NG-nitro-L-arginine （L-NA） reduced focal cerebral ischemic damage. The effect of L-NA on the contents of excitatory and inhibitory amino acid in the rat brain following cerebral ischemia is still unclear. OBJECTIVE： By evaluating the effect of NOS inhibitor, L-NA on the contents of aspartate, glutamate, glycine and γ-aminobutyric acid （GABA） in striatum, hippocampus and cortex in the rat brain following cerebral ischemia respectively, to investigate the beneficial effect of L-NA on cerebral ischemic injury and the possible mechanism. DESIGN： A randomized and controlled experiment SETTING ： Department of Pharmacology, Hebei Academy of Medical Sciences MATERIALS： A total of 42 male healthy SD rats （grade Ⅱ, weighting 250-300 g） were provided by the Experimental Animal Center of Hebei Province （Certification： 04036）. Aspartate, glutamate, glycine, GABA, L-NA and 2,3,5-triphenyltetrazolium chloride （TTC） were obtained from Sigma Chemicals Co, St Louis, MO, USA. HPLC-ultraviolet detector system consisted of Agilent 1100 HPLC. METHODS： The experiment was carried out in Department of Pharmrcology, Hebei Academy of Medical Sciences from June 2005 to June 2006. Rats were randomly divided into three groups： sham-operated group （n = 6）, ischemic group （n = 18）, L-NA group （n = 18）. The model of focal cerebral ischemia in rat was prepared with intraluminal line occlusion methods. In sham-operated rats, the external carotid artery was surgically prepared, but the filament was not inserted. Each group was further divided into 3 subgroups （n = 6 for each）： drugs were administrated at 2, 6 and 12 hours after the middle cerebral artery occlusion （MCAO） respectively. L-NA （20 mg/kg, ip） was administrated, twice a day, for 3 consecutive days. Same volume of normal saline was administrated in ischemic and sham operation groups. The changes of infarcted volume and the contents of amino acids were respectively assayed. Image analysis software was used for the measurement of the infarcted area. The results were expressed as a percentage of the infarcted volume of cerebral/volume of whole brain （IV%） in order to control for edema formation. The contents of aspartate, glutamate, glycine and GABA in striatum, hippocampus and cortex in the rat brain following cerebral ischemia were respectively measured by HPLC method. All data were analyzed with one-way ANOVA and Dunnett＇s test. MAIN OUTCOME MEASURES： （1） The volume of cerebral infarction; （2） The contents of aspartate, glutamate glycine and GABA in brain tissue after cerebral ischemia. RESULTS ： All 42 rats were involved in the final analysis. （1） Infarcted volume： Volume was 0 in sham-operated group. When L-NA was administrated at 2 and 6 hours after MCAO, the infarcted volume was （20.13±3.59）% and （23.12±5.84）% in L-NA group, which was not similar to that in ischemic group [（22.10±3.98）%, （25.38± 5.37）%, P〉 0.05]. However, the infarcted volume was markedly decreased compared with that of ischemic group when L-NA was administrated at 12 hours after MCAO [（26.11±3.55）% and （37.15±3.58）%, P 〈 0.01]. Changes of amino acid content： At 2 and 6 hours after ischemia, the contents of aspartate, glutamate, glycine and GABA in striatum, hippocampus and cortex in ischemic group were significantly increased compared with those in sham-operated group （ P〈 0.05-0.01）. However, contents in L-NA group were similar to those in ischemic group （P 〉 0.05）. At 12 hours after ischemia, the contents of aspartate [（0.21 ±0.06）, （0.36±0.05）, （0.29±0.12） mg/g] and glutamate [（0.55±0.06）, （0.78±0.10）, （0.52±0.10） mg/g] in striatum, hippocampus and cortex in L-NA group were significantly decreased compared with those in ischemic group [（0.49±0.17）, （0.63± 0.03）, （0.51±0.15） mg/g; （0.98±0.30）, （1.15±0.15）, （0.93±0.15） mg/g, P〈 0.05-0.01]. Glycine in hippocampus was （0.40±0.07） mg/g, which was higher than that in ischemic group [（0.21±0.07） mg/g, P 〈 0.05]. GABA in striatum, hippocampus and cortex was （0.93±0.10）, （0.62±0.12） and （0.81 ±0.10） mg/g, respectively, which was higher than that in ischemic group [（0.60±0.08）, （0.37±0.17）, （0.59±0.10） mg/g, P 〈 0.05-0.01]. CONCLUSION ： It may be concluded that L-NA have beneficial effect on ischemic cerebral injury in ischemic later stage in rats. The possible mechanism is that L-NA can decrease the contents of aspartate and glutamate, increase the contents of glycine and GABA.展开更多
Precise tuning of gene expression,accomplished by regulato ry networks of transcription factors,epigenetic modifiers,and microRNAs,is crucial for the proper neural development and function of the brain cells.The SOX t...Precise tuning of gene expression,accomplished by regulato ry networks of transcription factors,epigenetic modifiers,and microRNAs,is crucial for the proper neural development and function of the brain cells.The SOX transcription factors are involved in regulating diverse cellular processes during embryonic and adult neurogenesis,such as maintaining the cell stemness,cell prolife ration,cell fate decisions,and terminal diffe rentiation into neurons and glial cells.MicroRNAs represent a class of small non-coding RNAs that play important roles in the regulation of gene expression.Together with other gene regulatory factors,microRNAs regulate different processes during neurogenesis and orchestrate the spatial and temporal expression important for neurodevelopment.The emerging data point to a complex regulatory network between SOX transcription factors and microRNAs that govern distinct cellular activities in the developing and adult brain.Deregulated SOX/mic roRNA interplay in signaling pathways that influence the homeostasis and plasticity in the brain has been revealed in various brain pathologies,including neurodegenerative disorders,traumatic brain injury,and cancer.Therapeutic strategies that target SOX/microRNA interplay have emerged in recent years as a promising tool to target neural tissue regeneration and enhance neuro restoration.N umerous studies have confirmed complex intera ctions between microRNAs and SOX-specific mRNAs regulating key features of glioblastoma.Keeping in mind the crucial roles of SOX genes and microRNAs in neural development,we focus this review on SOX/microRNAs interplay in the brain during development and adulthood in physiological and pathological conditions.Special focus was made on their interplay in brain pathologies to summarize current knowledge and highlight potential future development of molecular therapies.展开更多
目的探究颈动脉支架植入术(CAS)后缺血性脑卒中患者脑组织灌注、神经影像学及相关因子变化。方法选取2021-01—2022-12邢台市第三医院收治的80例缺血性脑卒中患者为研究对象,分为CAS组和颈动脉内膜剥脱术(CEA)组各40例,对比2组患者治疗...目的探究颈动脉支架植入术(CAS)后缺血性脑卒中患者脑组织灌注、神经影像学及相关因子变化。方法选取2021-01—2022-12邢台市第三医院收治的80例缺血性脑卒中患者为研究对象,分为CAS组和颈动脉内膜剥脱术(CEA)组各40例,对比2组患者治疗前后脑组织灌注情况[峰值时间(TTP)、平均通过时间(MTT)、脑血流量(CBF)、脑血容量(CBV)]、颈动脉狭窄及血管内皮生长因子(VEGF)、超敏C反应蛋白(hs-CRP)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)等情况。结果治疗后2组患者TTP、MTT均降低,CBF、CBV均升高,CAS组较CEA组变化更显著(P<0.05)。治疗后2组患者颈动脉狭窄处血管内径测量结果均较治疗前增加,CAS组较CEA组变化更为显著(P<0.05)。治疗后2组患者VEGF、hs-CRP、TNF-α、IL-6水平均呈先升高后降低的趋势,治疗后1 d及7 d CEA组患者VEGF、hs-CRP、TNF-α、IL-6水平均高于CAS组(P<0.05)。结论CAS可改善缺血性脑卒中患者术后脑组织灌注及颈动脉狭窄处血管内径,对患者的相关因子水平影响较小,具有较好的治疗效果。展开更多
文摘Ischemic stroke is an important disease leading to death and disability for all human beings, and the key to its treatment lies in the early opening of obstructed vessels and restoration of perfusion to the local infarcted area. Intravenous thrombolysis with tissue plasminogen activator (tPA) is one of the effective therapies to achieve revascularization, but it faces strict indications with a narrow therapeutic time window, and significantly increases the incidence of hemorrhagic transformation, HT, after reperfusion of the infarcted foci, which greatly reduces the incidence of patients with ischemic stroke. which significantly increases the incidence of hemorrhagic transformation (HT) after reperfusion of the infarcted focus, greatly reducing patient utilization and clinical benefit. Since the mechanism of HT has not been fully elucidated, and the related molecular mechanisms are complex and interactive, there is no specific and effective therapy to avoid the occurrence of HT. In this article, we focus on the research progress on the mechanism of HT after tPA intravenous thrombolysis in ischemic stroke patients from the aspects of vascular integrity disruption, oxidative stress, and neuroinflammatory response and the corresponding therapeutic strategies, in order to improve the safety and prognosis of tPA intravenous thrombolysis in the clinic.
基金the Natural Sci-ence Foundation of HebeiProvince, No. C2005000840
文摘BACKGROUND： Nitric oxide synthase （NOS） inhibrtors have been widely used to investigate the role of NO on cerebral ischemic injury, but the results are controversial. Moreover, it has been considered to aggravate the ischemic neuronal damage with the release of excessively excitatory amino acids （EAA） during cerebral ischemia. On the other hand, some inhibitory amino acid is suggested to be important for the neuronal protection against ischemic brain damage. Our study has recently showed that treatment with the NOS inhibitor NG-nitro-L-arginine （L-NA） reduced focal cerebral ischemic damage. The effect of L-NA on the contents of excitatory and inhibitory amino acid in the rat brain following cerebral ischemia is still unclear. OBJECTIVE： By evaluating the effect of NOS inhibitor, L-NA on the contents of aspartate, glutamate, glycine and γ-aminobutyric acid （GABA） in striatum, hippocampus and cortex in the rat brain following cerebral ischemia respectively, to investigate the beneficial effect of L-NA on cerebral ischemic injury and the possible mechanism. DESIGN： A randomized and controlled experiment SETTING ： Department of Pharmacology, Hebei Academy of Medical Sciences MATERIALS： A total of 42 male healthy SD rats （grade Ⅱ, weighting 250-300 g） were provided by the Experimental Animal Center of Hebei Province （Certification： 04036）. Aspartate, glutamate, glycine, GABA, L-NA and 2,3,5-triphenyltetrazolium chloride （TTC） were obtained from Sigma Chemicals Co, St Louis, MO, USA. HPLC-ultraviolet detector system consisted of Agilent 1100 HPLC. METHODS： The experiment was carried out in Department of Pharmrcology, Hebei Academy of Medical Sciences from June 2005 to June 2006. Rats were randomly divided into three groups： sham-operated group （n = 6）, ischemic group （n = 18）, L-NA group （n = 18）. The model of focal cerebral ischemia in rat was prepared with intraluminal line occlusion methods. In sham-operated rats, the external carotid artery was surgically prepared, but the filament was not inserted. Each group was further divided into 3 subgroups （n = 6 for each）： drugs were administrated at 2, 6 and 12 hours after the middle cerebral artery occlusion （MCAO） respectively. L-NA （20 mg/kg, ip） was administrated, twice a day, for 3 consecutive days. Same volume of normal saline was administrated in ischemic and sham operation groups. The changes of infarcted volume and the contents of amino acids were respectively assayed. Image analysis software was used for the measurement of the infarcted area. The results were expressed as a percentage of the infarcted volume of cerebral/volume of whole brain （IV%） in order to control for edema formation. The contents of aspartate, glutamate, glycine and GABA in striatum, hippocampus and cortex in the rat brain following cerebral ischemia were respectively measured by HPLC method. All data were analyzed with one-way ANOVA and Dunnett＇s test. MAIN OUTCOME MEASURES： （1） The volume of cerebral infarction; （2） The contents of aspartate, glutamate glycine and GABA in brain tissue after cerebral ischemia. RESULTS ： All 42 rats were involved in the final analysis. （1） Infarcted volume： Volume was 0 in sham-operated group. When L-NA was administrated at 2 and 6 hours after MCAO, the infarcted volume was （20.13±3.59）% and （23.12±5.84）% in L-NA group, which was not similar to that in ischemic group [（22.10±3.98）%, （25.38± 5.37）%, P〉 0.05]. However, the infarcted volume was markedly decreased compared with that of ischemic group when L-NA was administrated at 12 hours after MCAO [（26.11±3.55）% and （37.15±3.58）%, P 〈 0.01]. Changes of amino acid content： At 2 and 6 hours after ischemia, the contents of aspartate, glutamate, glycine and GABA in striatum, hippocampus and cortex in ischemic group were significantly increased compared with those in sham-operated group （ P〈 0.05-0.01）. However, contents in L-NA group were similar to those in ischemic group （P 〉 0.05）. At 12 hours after ischemia, the contents of aspartate [（0.21 ±0.06）, （0.36±0.05）, （0.29±0.12） mg/g] and glutamate [（0.55±0.06）, （0.78±0.10）, （0.52±0.10） mg/g] in striatum, hippocampus and cortex in L-NA group were significantly decreased compared with those in ischemic group [（0.49±0.17）, （0.63± 0.03）, （0.51±0.15） mg/g; （0.98±0.30）, （1.15±0.15）, （0.93±0.15） mg/g, P〈 0.05-0.01]. Glycine in hippocampus was （0.40±0.07） mg/g, which was higher than that in ischemic group [（0.21±0.07） mg/g, P 〈 0.05]. GABA in striatum, hippocampus and cortex was （0.93±0.10）, （0.62±0.12） and （0.81 ±0.10） mg/g, respectively, which was higher than that in ischemic group [（0.60±0.08）, （0.37±0.17）, （0.59±0.10） mg/g, P 〈 0.05-0.01]. CONCLUSION ： It may be concluded that L-NA have beneficial effect on ischemic cerebral injury in ischemic later stage in rats. The possible mechanism is that L-NA can decrease the contents of aspartate and glutamate, increase the contents of glycine and GABA.
基金the Ministry of Education,Science and Technological Development of the Republic of Serbia(Agreement number 451-03-9/2021-14/200042,to MiS,DSN,MM,DD and MaS)the Serbian Academy of Sciences and Arts(Grant number F24,to MiS(PI),MM,DD and MaS)。
文摘Precise tuning of gene expression,accomplished by regulato ry networks of transcription factors,epigenetic modifiers,and microRNAs,is crucial for the proper neural development and function of the brain cells.The SOX transcription factors are involved in regulating diverse cellular processes during embryonic and adult neurogenesis,such as maintaining the cell stemness,cell prolife ration,cell fate decisions,and terminal diffe rentiation into neurons and glial cells.MicroRNAs represent a class of small non-coding RNAs that play important roles in the regulation of gene expression.Together with other gene regulatory factors,microRNAs regulate different processes during neurogenesis and orchestrate the spatial and temporal expression important for neurodevelopment.The emerging data point to a complex regulatory network between SOX transcription factors and microRNAs that govern distinct cellular activities in the developing and adult brain.Deregulated SOX/mic roRNA interplay in signaling pathways that influence the homeostasis and plasticity in the brain has been revealed in various brain pathologies,including neurodegenerative disorders,traumatic brain injury,and cancer.Therapeutic strategies that target SOX/microRNA interplay have emerged in recent years as a promising tool to target neural tissue regeneration and enhance neuro restoration.N umerous studies have confirmed complex intera ctions between microRNAs and SOX-specific mRNAs regulating key features of glioblastoma.Keeping in mind the crucial roles of SOX genes and microRNAs in neural development,we focus this review on SOX/microRNAs interplay in the brain during development and adulthood in physiological and pathological conditions.Special focus was made on their interplay in brain pathologies to summarize current knowledge and highlight potential future development of molecular therapies.
文摘目的探究颈动脉支架植入术(CAS)后缺血性脑卒中患者脑组织灌注、神经影像学及相关因子变化。方法选取2021-01—2022-12邢台市第三医院收治的80例缺血性脑卒中患者为研究对象,分为CAS组和颈动脉内膜剥脱术(CEA)组各40例,对比2组患者治疗前后脑组织灌注情况[峰值时间(TTP)、平均通过时间(MTT)、脑血流量(CBF)、脑血容量(CBV)]、颈动脉狭窄及血管内皮生长因子(VEGF)、超敏C反应蛋白(hs-CRP)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)等情况。结果治疗后2组患者TTP、MTT均降低,CBF、CBV均升高,CAS组较CEA组变化更显著(P<0.05)。治疗后2组患者颈动脉狭窄处血管内径测量结果均较治疗前增加,CAS组较CEA组变化更为显著(P<0.05)。治疗后2组患者VEGF、hs-CRP、TNF-α、IL-6水平均呈先升高后降低的趋势,治疗后1 d及7 d CEA组患者VEGF、hs-CRP、TNF-α、IL-6水平均高于CAS组(P<0.05)。结论CAS可改善缺血性脑卒中患者术后脑组织灌注及颈动脉狭窄处血管内径,对患者的相关因子水平影响较小,具有较好的治疗效果。
