The effects of minimally invasive surgery on the blood-brain barrier （BBB） of 30 patients with cerebral hemorrhage were investigated. Difference of the BBB index and serum MBP concentration were assessed in 15 cases...The effects of minimally invasive surgery on the blood-brain barrier （BBB） of 30 patients with cerebral hemorrhage were investigated. Difference of the BBB index and serum MBP concentration were assessed in 15 cases of conservative treatment group and 15 cases of minimally invasive surgery group. The BBB index in minimally invasive surgery group was significantly lower than in conservative treatment group （P〈0.05）, and the BBB index in the two treatment groups was significantly higher than in control group （P〈0.01）. Serum MBP concentration in minimally invasive surgery group was significantly lower than in conservative treatment group （P〈0.05）, and that in the two treatment groups was significantly higher than in control group （P〈0.01）. It was suggested the permeability of BBB in patients with cerebral hemorrhage was increased, and BBB index and serum MBP concentration in patients with cerebral hemorrhage were increased. Minimally invasive surgery can reduce the lesion of cytotoxicity to BBB and cerebral edema.展开更多
A global proteomics strategy was initiated to decipher molecular mechanisms associated with the blood-brain barrier (BBB) phenotype of the brain capillary endothelial cells. The different methods implemented were show...A global proteomics strategy was initiated to decipher molecular mechanisms associated with the blood-brain barrier (BBB) phenotype of the brain capillary endothelial cells. The different methods implemented were shown complementarily. The main results obtained using an in vitro BBB model allowed highlighting the role of several protein actors of cytoskeleton remodelling, the involvement of the asymmetric dimethylarginine pathway in regulating endothelial function and the role of tissue non-specific alkaline phosphatase in the regulation of endothelial permeability.展开更多
Ohjectire To examine the hypothesis of normal perjusion pressure breakthrough (NPPB). Methods A modified Spetzler carotid -jugular (CJ) fistula model was created to imitate NPPB. In 9 male adult Sprague- Dawley rats, ...Ohjectire To examine the hypothesis of normal perjusion pressure breakthrough (NPPB). Methods A modified Spetzler carotid -jugular (CJ) fistula model was created to imitate NPPB. In 9 male adult Sprague- Dawley rats, the ipsilateral vertebral artery and bilateral external carotid arteries were occluded. The period of hypoperfusion CJ fistula was extended to 14 weeks, as a modofcation of Spetzler model. The histological change were examtned under transmission electron microscope 14 weeks after creation of the listula. Results Ischemic histological changes such as increased pinocytosis, increased lucency of the basal lamina, and frank necrosis of the cerebral capillary were found in rats of CJ fistula group. Conclusion The findings in this study suggest that blood - braln barrier (BBB) was impaired by chronic hypoperfusion. The impaired BBB mny be one of the important causes of the NPPB phenomenon.展开更多
背景与目的:开放血脑屏障将为胶质瘤的综合治疗提供新的希望,本研究观察C6脑胶质瘤不同区域血-脑屏障(BBB)的通透性的变化、超微结构特征及紧密连接蛋白claudin-5的表达变化。方法:雄性SD大鼠,随机分为对照组和荷瘤组,采用立体定向方法...背景与目的:开放血脑屏障将为胶质瘤的综合治疗提供新的希望,本研究观察C6脑胶质瘤不同区域血-脑屏障(BBB)的通透性的变化、超微结构特征及紧密连接蛋白claudin-5的表达变化。方法:雄性SD大鼠,随机分为对照组和荷瘤组,采用立体定向方法在大鼠右侧尾状核接种C6细胞建立大鼠C6胶质瘤模型,于建模后第20天取肿瘤、肿瘤临近处(brain adjacent to tumor,BAT)即距肿瘤边界2mm以内及肿瘤远隔处(brain dis-tant to tumor,BDT)即2mm以外的大脑半球脑皮质3个部位的脑组织和对照鼠右侧尾状核正常脑组织,采用外源性硝酸镧透射电镜示踪法,观察BBB/BBTB超微结构特征;免疫组化法观察紧密连接蛋白claudin-5在正常鼠和荷瘤鼠各部位的表达变化。结果:(1)肿瘤处可见La3+通过血管内皮细胞的紧密连接渗透至血管腔外及脑间质裂隙内,BAT部分见La3+渗出至局部基底膜,大部分分布在血管腔内,而BDT及对照组正常脑组织La3+分布在血管腔内,血管内皮细胞紧密连接结构完整,基底膜呈线状连续,脑血管内皮细胞浆均未见La3+。(2)claudin-5在BDT与对照组脑组织表达丰富、连续;肿瘤处表达减弱,沿血管呈间断表达;BAT较正常脑组织表达下降,但仍呈连续状态。结论:正常脑组织血脑屏障稳定,通透性最低;肿瘤的周边存在不同程度的屏障;C6胶质瘤细胞的直接浸润可以降低内皮细胞紧密连接蛋白claudin-5,可能是诱导紧密连接破坏导致BBTB通透性增高的重要原因。展开更多
The pathology of ischemic stroke and the mechanism of thrombolytic therapy induced lethal hemorrhagic transformation(HT)involve disruption of the blood brain barrier(BBB).This study evaluated the effect of regulatory ...The pathology of ischemic stroke and the mechanism of thrombolytic therapy induced lethal hemorrhagic transformation(HT)involve disruption of the blood brain barrier(BBB).This study evaluated the effect of regulatory T cells(Tregs)transfer on ischemic stroke and rtPA-enhanced HT.In addition,we further investigated the mechanism underlying Tregafforded BBB protection.Cerebral ischemia was induced in mouse by suture middle cerebral artery occlusion(MCAO)for 1 h,or for 2 h followed by intravenous rtPA infusion leading to HT.Systemic administration of purified Tregs at 2,6,or 24 hours after the surgery,resulted in marked reduction of brain infarct and rtPA-induced cerebral hemorrhage.Treg-afforded neuroprotection was accompanied by attenuated blood-brain barrier(BBB)disruption during early stages of ischemia in these two different model types.Further studies suggested that Tregs inhibited the elevation of matrix metallopeptidase-9(MMP9)and chemokine(C-C motif)ligand 2(CCL2)expression after stroke,thus preventing proteolytic damage of the BBB.Using MMP9 knockout and CCL2 knockout mice,we found that both molecules partially contribute to the protective actions of Tregs.Using In vitro model of BBB,we confirmed that Tregs inhibited tPA-induced endothelial expression of CCL2 and protected BBB against ischemic challenge.Clinical data revealed a significant decrease in the number of circulating Tregs upon stroke onset.The prolonged loss of circulating Tregs is correlated with poor stroke outcomes.It is concluded that Tregs reduces ischemia and rtPA-induced BBB damage by two inhibitory mechanisms targeting both CCL2 and MMP9.Tregs may represent a potent cell-based therapy to decrease the brain infarct and increase the safety of thrombolytic treatment for stroke.展开更多
Glioblastoma multiforme(GBM) is the most common primary malignant brain tumor, and it is associated with poor prognosis. Its characteristics of being highly invasive and undergoing heterogeneous genetic mutation, as w...Glioblastoma multiforme(GBM) is the most common primary malignant brain tumor, and it is associated with poor prognosis. Its characteristics of being highly invasive and undergoing heterogeneous genetic mutation, as well as the presence of the blood–brain barrier(BBB), have reduced the efficacy of GBM treatment. The emergence of a novel therapeutic method, namely, sonodynamic therapy(SDT), provides a promising strategy for eradicating tumors via activated sonosensitizers coupled with low-intensity ultrasound. SDT can provide tumor killing effects for deep-seated tumors, such as brain tumors. However, conventional sonosensitizers cannot effectively reach the tumor region and kill additional tumor cells, especially brain tumor cells. Efforts should be made to develop a method to help therapeutic agents pass through the BBB and accumulate in brain tumors. With the development of novel multifunctional nanosensitizers and newly emerging combination strategies, the killing ability and selectivity of SDT have greatly improved and are accompanied with fewer side effects. In this review, we systematically summarize the findings of previous studies on SDT for GBM, with a focus on recent developments and promising directions for future research.展开更多
The cerebral blood flow（CBF） alterations related to sound-induced opening of the blood–brain barrier（BBB） in adult mice are studied using laser speckle contrast imaging（LSCI） and wavelet analysis of vascular ph...The cerebral blood flow（CBF） alterations related to sound-induced opening of the blood–brain barrier（BBB） in adult mice are studied using laser speckle contrast imaging（LSCI） and wavelet analysis of vascular physiology.The results clearly show that the opening of the BBB is accompanied by the changes of venous but not microvessel circulation in the brain. The elevation of the BBB permeability is associated with the decrease of venous CBF and the increase of its complexity. These data suggest that the cerebral veins rather than microvessels are sensitive components of the CBF related to the opening BBB.展开更多
文摘The effects of minimally invasive surgery on the blood-brain barrier （BBB） of 30 patients with cerebral hemorrhage were investigated. Difference of the BBB index and serum MBP concentration were assessed in 15 cases of conservative treatment group and 15 cases of minimally invasive surgery group. The BBB index in minimally invasive surgery group was significantly lower than in conservative treatment group （P〈0.05）, and the BBB index in the two treatment groups was significantly higher than in control group （P〈0.01）. Serum MBP concentration in minimally invasive surgery group was significantly lower than in conservative treatment group （P〈0.05）, and that in the two treatment groups was significantly higher than in control group （P〈0.01）. It was suggested the permeability of BBB in patients with cerebral hemorrhage was increased, and BBB index and serum MBP concentration in patients with cerebral hemorrhage were increased. Minimally invasive surgery can reduce the lesion of cytotoxicity to BBB and cerebral edema.
文摘A global proteomics strategy was initiated to decipher molecular mechanisms associated with the blood-brain barrier (BBB) phenotype of the brain capillary endothelial cells. The different methods implemented were shown complementarily. The main results obtained using an in vitro BBB model allowed highlighting the role of several protein actors of cytoskeleton remodelling, the involvement of the asymmetric dimethylarginine pathway in regulating endothelial function and the role of tissue non-specific alkaline phosphatase in the regulation of endothelial permeability.
文摘Ohjectire To examine the hypothesis of normal perjusion pressure breakthrough (NPPB). Methods A modified Spetzler carotid -jugular (CJ) fistula model was created to imitate NPPB. In 9 male adult Sprague- Dawley rats, the ipsilateral vertebral artery and bilateral external carotid arteries were occluded. The period of hypoperfusion CJ fistula was extended to 14 weeks, as a modofcation of Spetzler model. The histological change were examtned under transmission electron microscope 14 weeks after creation of the listula. Results Ischemic histological changes such as increased pinocytosis, increased lucency of the basal lamina, and frank necrosis of the cerebral capillary were found in rats of CJ fistula group. Conclusion The findings in this study suggest that blood - braln barrier (BBB) was impaired by chronic hypoperfusion. The impaired BBB mny be one of the important causes of the NPPB phenomenon.
文摘背景与目的:开放血脑屏障将为胶质瘤的综合治疗提供新的希望,本研究观察C6脑胶质瘤不同区域血-脑屏障(BBB)的通透性的变化、超微结构特征及紧密连接蛋白claudin-5的表达变化。方法:雄性SD大鼠,随机分为对照组和荷瘤组,采用立体定向方法在大鼠右侧尾状核接种C6细胞建立大鼠C6胶质瘤模型,于建模后第20天取肿瘤、肿瘤临近处(brain adjacent to tumor,BAT)即距肿瘤边界2mm以内及肿瘤远隔处(brain dis-tant to tumor,BDT)即2mm以外的大脑半球脑皮质3个部位的脑组织和对照鼠右侧尾状核正常脑组织,采用外源性硝酸镧透射电镜示踪法,观察BBB/BBTB超微结构特征;免疫组化法观察紧密连接蛋白claudin-5在正常鼠和荷瘤鼠各部位的表达变化。结果:(1)肿瘤处可见La3+通过血管内皮细胞的紧密连接渗透至血管腔外及脑间质裂隙内,BAT部分见La3+渗出至局部基底膜,大部分分布在血管腔内,而BDT及对照组正常脑组织La3+分布在血管腔内,血管内皮细胞紧密连接结构完整,基底膜呈线状连续,脑血管内皮细胞浆均未见La3+。(2)claudin-5在BDT与对照组脑组织表达丰富、连续;肿瘤处表达减弱,沿血管呈间断表达;BAT较正常脑组织表达下降,但仍呈连续状态。结论:正常脑组织血脑屏障稳定,通透性最低;肿瘤的周边存在不同程度的屏障;C6胶质瘤细胞的直接浸润可以降低内皮细胞紧密连接蛋白claudin-5,可能是诱导紧密连接破坏导致BBTB通透性增高的重要原因。
文摘The pathology of ischemic stroke and the mechanism of thrombolytic therapy induced lethal hemorrhagic transformation(HT)involve disruption of the blood brain barrier(BBB).This study evaluated the effect of regulatory T cells(Tregs)transfer on ischemic stroke and rtPA-enhanced HT.In addition,we further investigated the mechanism underlying Tregafforded BBB protection.Cerebral ischemia was induced in mouse by suture middle cerebral artery occlusion(MCAO)for 1 h,or for 2 h followed by intravenous rtPA infusion leading to HT.Systemic administration of purified Tregs at 2,6,or 24 hours after the surgery,resulted in marked reduction of brain infarct and rtPA-induced cerebral hemorrhage.Treg-afforded neuroprotection was accompanied by attenuated blood-brain barrier(BBB)disruption during early stages of ischemia in these two different model types.Further studies suggested that Tregs inhibited the elevation of matrix metallopeptidase-9(MMP9)and chemokine(C-C motif)ligand 2(CCL2)expression after stroke,thus preventing proteolytic damage of the BBB.Using MMP9 knockout and CCL2 knockout mice,we found that both molecules partially contribute to the protective actions of Tregs.Using In vitro model of BBB,we confirmed that Tregs inhibited tPA-induced endothelial expression of CCL2 and protected BBB against ischemic challenge.Clinical data revealed a significant decrease in the number of circulating Tregs upon stroke onset.The prolonged loss of circulating Tregs is correlated with poor stroke outcomes.It is concluded that Tregs reduces ischemia and rtPA-induced BBB damage by two inhibitory mechanisms targeting both CCL2 and MMP9.Tregs may represent a potent cell-based therapy to decrease the brain infarct and increase the safety of thrombolytic treatment for stroke.
基金partially supported by the National Natural Science Foundation of China(81702457)the Clinical Medical University and Hospital Joint Construction of Disciplinary Projects 2021(2021lcxk017)+4 种基金the Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer(2020B121201004)the Outstanding Youths Development Scheme of Nanfang Hospital,Southern Medical University(2021J008)the Basic and Clinical Cooperative Research and Promotion Program of Anhui Medical University(2021xkjT028)the Open Fund of Key Laboratory of Antiinflammatory and Immune Medicine(KFJJ-2021-11)Grants for Scientific Research of BSKY from Anhui Medical University(1406012201)。
文摘Glioblastoma multiforme(GBM) is the most common primary malignant brain tumor, and it is associated with poor prognosis. Its characteristics of being highly invasive and undergoing heterogeneous genetic mutation, as well as the presence of the blood–brain barrier(BBB), have reduced the efficacy of GBM treatment. The emergence of a novel therapeutic method, namely, sonodynamic therapy(SDT), provides a promising strategy for eradicating tumors via activated sonosensitizers coupled with low-intensity ultrasound. SDT can provide tumor killing effects for deep-seated tumors, such as brain tumors. However, conventional sonosensitizers cannot effectively reach the tumor region and kill additional tumor cells, especially brain tumor cells. Efforts should be made to develop a method to help therapeutic agents pass through the BBB and accumulate in brain tumors. With the development of novel multifunctional nanosensitizers and newly emerging combination strategies, the killing ability and selectivity of SDT have greatly improved and are accompanied with fewer side effects. In this review, we systematically summarize the findings of previous studies on SDT for GBM, with a focus on recent developments and promising directions for future research.
基金supported by the Grant of Russian Science Foundation No 17-15-01263supported by the Open Research Fund of Key Laboratory for Biomedical Photonics,HUST,Ministry of Education,China
文摘The cerebral blood flow（CBF） alterations related to sound-induced opening of the blood–brain barrier（BBB） in adult mice are studied using laser speckle contrast imaging（LSCI） and wavelet analysis of vascular physiology.The results clearly show that the opening of the BBB is accompanied by the changes of venous but not microvessel circulation in the brain. The elevation of the BBB permeability is associated with the decrease of venous CBF and the increase of its complexity. These data suggest that the cerebral veins rather than microvessels are sensitive components of the CBF related to the opening BBB.
