A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researche...A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researchers have begun to focus on nanocarriers and other brain-targeting drug delivery systems.In this review,we summarize the epidemiology,basic pathophysiology,current clinical treatment,the establishment of models,and the evaluation indicators that are commonly used for traumatic brain injury.We also report the current status of traumatic brain injury when treated with nanocarriers such as liposomes and vesicles.Nanocarriers can overcome a variety of key biological barriers,improve drug bioavailability,increase intracellular penetration and retention time,achieve drug enrichment,control drug release,and achieve brain-targeting drug delivery.However,the application of nanocarriers remains in the basic research stage and has yet to be fully translated to the clinic.展开更多
Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its appl...Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains controversial.Here,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy.Cognitive assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise.Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier.In summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.展开更多
P2X4 and P2X7 receptors play an important role in neuropathic pain after spinal cord injury. Regulation of P2X4 and P2X7 receptors can obviously reduce pain hypersensitivity after injury. To investigate the role of ne...P2X4 and P2X7 receptors play an important role in neuropathic pain after spinal cord injury. Regulation of P2X4 and P2X7 receptors can obviously reduce pain hypersensitivity after injury. To investigate the role of neural stem cell transplantation on P2X receptor-mediated neuropathic pain and explore related mechanisms, a rat model of spinal cord injury was prepared using the free-falling heavy body method with spinal cord segment 10 as the center. Neural stem cells were injected into the injured spinal cord segment using a micro-syringe. Expression levels of P2X4 and P2X7 receptors, neurofilament protein, and glial fibrillary acidic protein were determined by immunohistochemistry and western blot assay. In addition, sensory function was quantitatively assessed by current perception threshold. The Basso-Beattie-Bresnahan locomotor rating scale was used to assess neuropathological pain. The results showed that 4 weeks after neural stem cell transplantation, expression of neurofilament protein in the injured segment was markedly increased, while expression of glial fibrillary acidic protein and P2X4 and P2X7 receptors was decreased. At this time point, motor and sensory functions of rats were obviously improved, and neuropathic pain was alleviated. These findings demonstrated that neural stem cell transplantation reduced overexpression of P2X4 and P2X7 receptors, activated locomotor and sensory function reconstruction, and played an important role in neuropathic pain regulation after spinal cord injury. Therefore, neural stem cell transplantation is one potential option for relieving neuropathic pain mediated by P2X receptors.展开更多
目的:探讨XMU-MP-1(Xiamen University-inhibitor of mammalian sterile 20-like kinase protein 1)对氧糖剥夺(OGD)损伤后小胶质细胞M1/M2极化平衡的调节作用。方法采用OGD法诱导BV2细胞损伤。实验分为6组:对照组、模型组、MST1/2 siRN...目的:探讨XMU-MP-1(Xiamen University-inhibitor of mammalian sterile 20-like kinase protein 1)对氧糖剥夺(OGD)损伤后小胶质细胞M1/M2极化平衡的调节作用。方法采用OGD法诱导BV2细胞损伤。实验分为6组:对照组、模型组、MST1/2 siRNA组和低、中、高剂量实验组(分别给予1.25、5.0和20.0μg·mL^(-1) XMU-MP-1)。采用MTT法测细胞活力,ELISA测细胞上清液中TNF-α、IL-6和IL-1β表达,qRT-PCR测M1和M2标志物的mRNA表达,流式细胞术测CD206表达,蛋白印迹法测MST1、LATS1和YAP蛋白表达。结果与模型组相比,XMU-MP-1抑制BV2细胞增殖,显著降低TNF-α、IL-6和IL-1β的表达水平,下调MCP-1、IL-6、TNF-α和i NOS mRNA的表达,上调CD206、IL-10、TGF-β、IL-10和YM1 mRNA表达,降低MST1和LAST 1蛋白表达,上调YAP和CD206表达。结论XMU-MP-1通过调控MST1/2的磷酸化,调节OGD损伤后的BV2细胞M1/M2极化平衡,为神经炎症靶点药物研发提供理论基础。展开更多
背景脑出血具有高发病率、高致残率、高死亡率的特点,脑出血后的炎症反应是造成继发性脑损伤的重要因素,影响患者的预后。虾青素具备抗炎、抗氧化等生物学作用,并能穿过血脑屏障,对多种神经系统疾病具有神经保护作用。目的观察虾青素对...背景脑出血具有高发病率、高致残率、高死亡率的特点,脑出血后的炎症反应是造成继发性脑损伤的重要因素,影响患者的预后。虾青素具备抗炎、抗氧化等生物学作用,并能穿过血脑屏障,对多种神经系统疾病具有神经保护作用。目的观察虾青素对大鼠脑出血后小胶质细胞活化的影响。方法64只大鼠尾状核注入自体血构建脑出血模型,随机分为假手术组、脑出血组、虾青素低剂量组、虾青素高剂量组,每组16只。虾青素低、高剂量组大鼠分别予以虾青素20 mg/kg、40 mg/kg灌胃,假手术组、脑出血组则给予等体积花生油溶剂,第3天行神经功能评分后处死大鼠。干湿重法测大鼠脑组织含水量,HE染色观察大鼠脑血肿周围组织病理变化,免疫荧光观察小胶质细胞变化,ELISA测定大鼠脑组织肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)的表达水平,Western blot测Iba-1、NF-κB蛋白含量。结果与假手术组比较,脑出血组神经功能评分明显降低(17.44±0.89 vs 7.56±1.55,P<0.05),脑组织含水量增加(77.72%±0.89%vs 84.60%±0.90%,P<0.05),细胞溶解、坏死,可见大量炎症细胞浸润;小胶质细胞被激活,NF-κB(0.092±0.020 vs 0.595±0.028)、TNF-α[(134.83±15.04)pg/mL vs(781.20±100.29)pg/mL]、IL-1β[(170.19±13.19)pg/mL vs(655.11±61.98)pg/mL]表达升高(P<0.05);与脑出血组相比,虾青素低、高剂量组大鼠神经功能评分(7.56±1.55 vs 9.5±1.46、10.75±1.69)及脑组织病理学改变均得到改善,脑组织含水量(84.60%±0.90%vs 82.43%±0.52%、81.04%±0.98%)降低(P<0.05),脑组织NF-κB(0.595±0.028 vs 0.479±0.03、0.387±0.031)、TNF-α[(781.20±100.29)pg/mL vs(445.40±66.34)pg/mL、(346.66±39.13)pg/mL]、IL-1β[(655.11±61.98)pg/mL vs(456.99±52.83)pg/mL、(331.46±30.90)pg/mL]表达下调(P<0.05)。结论虾青素可能通过抑制小胶质细胞活化从而减轻炎症反应及脑水肿程度,对脑出血大鼠具�展开更多
基金supported by grants from the National Natural Science Foundation of China (No. 81471330)the National Students’ Innovation and Entrepreneurship Training Program of China (No. 201810313015), Top-notch Academic Programs Project of Jiangsu Higher Education Institutions (No. PPZY2015B161)National Demonstration Center for Experimental Basic Medical Science Education (Xuzhou Medical University), China (No. 201810313014Z)
基金supported by the Natural Science Foundation of Beijing,No.L222126(to LD)。
文摘A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researchers have begun to focus on nanocarriers and other brain-targeting drug delivery systems.In this review,we summarize the epidemiology,basic pathophysiology,current clinical treatment,the establishment of models,and the evaluation indicators that are commonly used for traumatic brain injury.We also report the current status of traumatic brain injury when treated with nanocarriers such as liposomes and vesicles.Nanocarriers can overcome a variety of key biological barriers,improve drug bioavailability,increase intracellular penetration and retention time,achieve drug enrichment,control drug release,and achieve brain-targeting drug delivery.However,the application of nanocarriers remains in the basic research stage and has yet to be fully translated to the clinic.
基金supported by STI2030-Major Projects,No.2022ZD0207600 (to LZ)the National Natural Science Foundation of China,Nos.821 71446 (to JY),U22A20301 (to KFS),32070955 (to LZ)+1 种基金Guangdong Basic and Applied Basic Research Foundation,No.202381515040015 (to LZ)Science and Technology Program of Guangzhou of China,No.202007030012 (to KFS and LZ)
文摘Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains controversial.Here,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy.Cognitive assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise.Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier.In summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.
基金financially supported by the Natural Science Foundation of Shandong Province of China,No.ZR2014HM046(to ZCZ),ZR2015HL113(to XJD),and ZR2014HL101(to XYW)the Science and Technology Development Project of Taian City of China,No.2015NS2183(to XJD)
文摘P2X4 and P2X7 receptors play an important role in neuropathic pain after spinal cord injury. Regulation of P2X4 and P2X7 receptors can obviously reduce pain hypersensitivity after injury. To investigate the role of neural stem cell transplantation on P2X receptor-mediated neuropathic pain and explore related mechanisms, a rat model of spinal cord injury was prepared using the free-falling heavy body method with spinal cord segment 10 as the center. Neural stem cells were injected into the injured spinal cord segment using a micro-syringe. Expression levels of P2X4 and P2X7 receptors, neurofilament protein, and glial fibrillary acidic protein were determined by immunohistochemistry and western blot assay. In addition, sensory function was quantitatively assessed by current perception threshold. The Basso-Beattie-Bresnahan locomotor rating scale was used to assess neuropathological pain. The results showed that 4 weeks after neural stem cell transplantation, expression of neurofilament protein in the injured segment was markedly increased, while expression of glial fibrillary acidic protein and P2X4 and P2X7 receptors was decreased. At this time point, motor and sensory functions of rats were obviously improved, and neuropathic pain was alleviated. These findings demonstrated that neural stem cell transplantation reduced overexpression of P2X4 and P2X7 receptors, activated locomotor and sensory function reconstruction, and played an important role in neuropathic pain regulation after spinal cord injury. Therefore, neural stem cell transplantation is one potential option for relieving neuropathic pain mediated by P2X receptors.
文摘目的:探讨XMU-MP-1(Xiamen University-inhibitor of mammalian sterile 20-like kinase protein 1)对氧糖剥夺(OGD)损伤后小胶质细胞M1/M2极化平衡的调节作用。方法采用OGD法诱导BV2细胞损伤。实验分为6组:对照组、模型组、MST1/2 siRNA组和低、中、高剂量实验组(分别给予1.25、5.0和20.0μg·mL^(-1) XMU-MP-1)。采用MTT法测细胞活力,ELISA测细胞上清液中TNF-α、IL-6和IL-1β表达,qRT-PCR测M1和M2标志物的mRNA表达,流式细胞术测CD206表达,蛋白印迹法测MST1、LATS1和YAP蛋白表达。结果与模型组相比,XMU-MP-1抑制BV2细胞增殖,显著降低TNF-α、IL-6和IL-1β的表达水平,下调MCP-1、IL-6、TNF-α和i NOS mRNA的表达,上调CD206、IL-10、TGF-β、IL-10和YM1 mRNA表达,降低MST1和LAST 1蛋白表达,上调YAP和CD206表达。结论XMU-MP-1通过调控MST1/2的磷酸化,调节OGD损伤后的BV2细胞M1/M2极化平衡,为神经炎症靶点药物研发提供理论基础。
文摘背景脑出血具有高发病率、高致残率、高死亡率的特点,脑出血后的炎症反应是造成继发性脑损伤的重要因素,影响患者的预后。虾青素具备抗炎、抗氧化等生物学作用,并能穿过血脑屏障,对多种神经系统疾病具有神经保护作用。目的观察虾青素对大鼠脑出血后小胶质细胞活化的影响。方法64只大鼠尾状核注入自体血构建脑出血模型,随机分为假手术组、脑出血组、虾青素低剂量组、虾青素高剂量组,每组16只。虾青素低、高剂量组大鼠分别予以虾青素20 mg/kg、40 mg/kg灌胃,假手术组、脑出血组则给予等体积花生油溶剂,第3天行神经功能评分后处死大鼠。干湿重法测大鼠脑组织含水量,HE染色观察大鼠脑血肿周围组织病理变化,免疫荧光观察小胶质细胞变化,ELISA测定大鼠脑组织肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)的表达水平,Western blot测Iba-1、NF-κB蛋白含量。结果与假手术组比较,脑出血组神经功能评分明显降低(17.44±0.89 vs 7.56±1.55,P<0.05),脑组织含水量增加(77.72%±0.89%vs 84.60%±0.90%,P<0.05),细胞溶解、坏死,可见大量炎症细胞浸润;小胶质细胞被激活,NF-κB(0.092±0.020 vs 0.595±0.028)、TNF-α[(134.83±15.04)pg/mL vs(781.20±100.29)pg/mL]、IL-1β[(170.19±13.19)pg/mL vs(655.11±61.98)pg/mL]表达升高(P<0.05);与脑出血组相比,虾青素低、高剂量组大鼠神经功能评分(7.56±1.55 vs 9.5±1.46、10.75±1.69)及脑组织病理学改变均得到改善,脑组织含水量(84.60%±0.90%vs 82.43%±0.52%、81.04%±0.98%)降低(P<0.05),脑组织NF-κB(0.595±0.028 vs 0.479±0.03、0.387±0.031)、TNF-α[(781.20±100.29)pg/mL vs(445.40±66.34)pg/mL、(346.66±39.13)pg/mL]、IL-1β[(655.11±61.98)pg/mL vs(456.99±52.83)pg/mL、(331.46±30.90)pg/mL]表达下调(P<0.05)。结论虾青素可能通过抑制小胶质细胞活化从而减轻炎症反应及脑水肿程度,对脑出血大鼠具�
