Radiation therapy is considered the most effective non-surgical treatment for brain tumors.However,there are no available treatments for radiation-induced brain injury.Bisdemethoxycurcumin(BDMC)is a demethoxy derivati...Radiation therapy is considered the most effective non-surgical treatment for brain tumors.However,there are no available treatments for radiation-induced brain injury.Bisdemethoxycurcumin(BDMC)is a demethoxy derivative of curcumin that has anti-proliferative,anti-inflammatory,and anti-oxidant properties.To determine whether BDMC has the potential to treat radiation-induced brain injury,in this study,we established a rat model of radiation-induced brain injury by administe ring a single 30-Gy vertical dose of irradiation to the whole brain,followed by intraperitoneal injection of 500μL of a 100 mg/kg BDMC solution every day for 5 successive weeks.Our res ults showed that BDMC increased the body weight of rats with radiation-induced brain injury,improved lea rning and memory,attenuated brain edema,inhibited astrocyte activation,and reduced oxidative stress.These findings suggest that BDMC protects against radiationinduced brain injury.展开更多
Despite years of effort,no effective acute phase treatment has been discovered for traumatic brain injury.One impediment to successful drug development is entangled secondary injury pathways.Here we show that protein ...Despite years of effort,no effective acute phase treatment has been discovered for traumatic brain injury.One impediment to successful drug development is entangled secondary injury pathways.Here we show that protein S,a natural multifunctional protein that regulates coagulation,inflammation,and apoptosis,is able to reduce the extent of multiple secondary injuries in traumatic brain injury,and therefore improve prognosis.Mice subjected to controlled cortical impact were treated acutely(10–15 minutes post-injury)with a single dose of either protein S(1 mg/kg)or vehicle phosphate buffered saline via intravenous injection.At 24 hours post-injury,compared to the non-treated group,the protein S treated group showed substantial improvement of edema and fine motor coordination,as well as mitigation of progressive tissue loss.Immunohistochemistry and western blot targeting caspase-3,B-cell lymphoma 2(Bcl-2)along with terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assay revealed that apoptosis was suppressed in treated animals.Immunohistochemistry targeting CD11 b showed limited leukocyte infiltration in the protein S-treated group.Moreover,protein S treatment increased the ipsilesional expression of aquaporin-4,which may be the underlying mechanism of its function in reducing edema.These results indicate that immediate intravenous protein S treatment after controlled cortical impact is beneficial to traumatic brain injury prognosis.Animal Use Protocols(AUPs)were approved by the University Committee on Animal Resources(UCAR)of University of Rochester Medical Center(approval No.UCAR-2008-102 R)on November 12,2013.展开更多
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. We identify High Mobility Group Box 1 (HMGB1) as a novel causative factor in the development of cerebral oedema, mediating coagulation...Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. We identify High Mobility Group Box 1 (HMGB1) as a novel causative factor in the development of cerebral oedema, mediating coagulation, preventing secondary brain damage as well as serving as a novel therapeutic target to limit secondary neurological injury after TBI. As a prototypical danger associated molecular patterns (DAMP), HMGB1 is released from necrotic neurons via a NR2B-mediated mechanism during TBI. The secretion of HMGB1 requires severe injury and tissue hypoperfusion, and is associated with posttraumatic coagulation abnormalities, activation of complement and severe systemic inflammatory response. HMGB1 is clinically associated with elevated intracranial pressure (ICP) in patients and functionally promoted cerebral edema after TBI. The detrimental effects of HMGB1 is mediated at least in part between activation of microglial toll-like receptor 4 (TLR4) and the subsequent expression of the astrocytic water channel aquaporin-4 (AQP4). Anti-HMGB1mAb remarkably inhibited fluid percussion-induced brain edema by inhibiting HMGB1 translocation, protection of blood-brain barrier (BBB) integrity, suppression of inflammatory molecule expression and improvement of motor function. Our review demonstrates the pathological role of HMGB1 as well as the possible therapeutic valve of HMGB1 in patients with TBI.展开更多
【目的】探讨步长脑心通对脑缺血的保护作用机制。【方法】选用Wistar大鼠,随机分为正常组、假手术组、模型组与治疗组,再分为12 h和24 h 2个亚组,治疗组给予步长脑心通灌胃(剂量为0.45 g.kg-1.d-1);采用大脑中动脉线栓法复制大鼠脑缺...【目的】探讨步长脑心通对脑缺血的保护作用机制。【方法】选用Wistar大鼠,随机分为正常组、假手术组、模型组与治疗组,再分为12 h和24 h 2个亚组,治疗组给予步长脑心通灌胃(剂量为0.45 g.kg-1.d-1);采用大脑中动脉线栓法复制大鼠脑缺血再灌注模型,应用免疫组织化学SP法检测大鼠脑组织一氧化氮合酶iNOS、eNOS的表达,采用图像分析仪测定光密度值,光镜下分析阳性细胞百分率。【结果】与模型组比较,治疗组iNOS表达显著降低(P<0.05),eNOS表达显著增高(P<0.05)。【结论】步长脑心通能降低脑缺血再灌注大鼠脑组织iNOS表达、增强eNOS表达,从而抑制神经细胞凋亡,发挥脑保护作用。展开更多
基金supported by the National Natural Science Foundation of China,No.82002400(to GJZ)Scientific Research Project of Hu nan Health Committee,No.20201911and No.20200469(both to ZJX)+2 种基金Scientific Research Project of Hunan Health Committee,No.20211411761(to HMW)the Natural Science Foundation of Hunan Province,No.2020JJ5512(to GJZ)a grant from Clinical Medical Technology Innovation Guidance Project in Hunan Province,No.2020SK51822(to ZJX)。
文摘Radiation therapy is considered the most effective non-surgical treatment for brain tumors.However,there are no available treatments for radiation-induced brain injury.Bisdemethoxycurcumin(BDMC)is a demethoxy derivative of curcumin that has anti-proliferative,anti-inflammatory,and anti-oxidant properties.To determine whether BDMC has the potential to treat radiation-induced brain injury,in this study,we established a rat model of radiation-induced brain injury by administe ring a single 30-Gy vertical dose of irradiation to the whole brain,followed by intraperitoneal injection of 500μL of a 100 mg/kg BDMC solution every day for 5 successive weeks.Our res ults showed that BDMC increased the body weight of rats with radiation-induced brain injury,improved lea rning and memory,attenuated brain edema,inhibited astrocyte activation,and reduced oxidative stress.These findings suggest that BDMC protects against radiationinduced brain injury.
基金supported in part by a University of Rochester Institutional Grant(2011NSG-Huang,to JHH)National Institute of Health(NIH-R01-NS-067435,to JHH)the Hellen Vosberg McCrillus Plummer and Robert Edward Lee Plummer,Jr,Endowment fund from Baylor Scott&White Medical Center(to JHH)。
文摘Despite years of effort,no effective acute phase treatment has been discovered for traumatic brain injury.One impediment to successful drug development is entangled secondary injury pathways.Here we show that protein S,a natural multifunctional protein that regulates coagulation,inflammation,and apoptosis,is able to reduce the extent of multiple secondary injuries in traumatic brain injury,and therefore improve prognosis.Mice subjected to controlled cortical impact were treated acutely(10–15 minutes post-injury)with a single dose of either protein S(1 mg/kg)or vehicle phosphate buffered saline via intravenous injection.At 24 hours post-injury,compared to the non-treated group,the protein S treated group showed substantial improvement of edema and fine motor coordination,as well as mitigation of progressive tissue loss.Immunohistochemistry and western blot targeting caspase-3,B-cell lymphoma 2(Bcl-2)along with terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assay revealed that apoptosis was suppressed in treated animals.Immunohistochemistry targeting CD11 b showed limited leukocyte infiltration in the protein S-treated group.Moreover,protein S treatment increased the ipsilesional expression of aquaporin-4,which may be the underlying mechanism of its function in reducing edema.These results indicate that immediate intravenous protein S treatment after controlled cortical impact is beneficial to traumatic brain injury prognosis.Animal Use Protocols(AUPs)were approved by the University Committee on Animal Resources(UCAR)of University of Rochester Medical Center(approval No.UCAR-2008-102 R)on November 12,2013.
文摘Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. We identify High Mobility Group Box 1 (HMGB1) as a novel causative factor in the development of cerebral oedema, mediating coagulation, preventing secondary brain damage as well as serving as a novel therapeutic target to limit secondary neurological injury after TBI. As a prototypical danger associated molecular patterns (DAMP), HMGB1 is released from necrotic neurons via a NR2B-mediated mechanism during TBI. The secretion of HMGB1 requires severe injury and tissue hypoperfusion, and is associated with posttraumatic coagulation abnormalities, activation of complement and severe systemic inflammatory response. HMGB1 is clinically associated with elevated intracranial pressure (ICP) in patients and functionally promoted cerebral edema after TBI. The detrimental effects of HMGB1 is mediated at least in part between activation of microglial toll-like receptor 4 (TLR4) and the subsequent expression of the astrocytic water channel aquaporin-4 (AQP4). Anti-HMGB1mAb remarkably inhibited fluid percussion-induced brain edema by inhibiting HMGB1 translocation, protection of blood-brain barrier (BBB) integrity, suppression of inflammatory molecule expression and improvement of motor function. Our review demonstrates the pathological role of HMGB1 as well as the possible therapeutic valve of HMGB1 in patients with TBI.
文摘【目的】探讨步长脑心通对脑缺血的保护作用机制。【方法】选用Wistar大鼠,随机分为正常组、假手术组、模型组与治疗组,再分为12 h和24 h 2个亚组,治疗组给予步长脑心通灌胃(剂量为0.45 g.kg-1.d-1);采用大脑中动脉线栓法复制大鼠脑缺血再灌注模型,应用免疫组织化学SP法检测大鼠脑组织一氧化氮合酶iNOS、eNOS的表达,采用图像分析仪测定光密度值,光镜下分析阳性细胞百分率。【结果】与模型组比较,治疗组iNOS表达显著降低(P<0.05),eNOS表达显著增高(P<0.05)。【结论】步长脑心通能降低脑缺血再灌注大鼠脑组织iNOS表达、增强eNOS表达,从而抑制神经细胞凋亡,发挥脑保护作用。
