Aim:The effects of tirofiban combined with nicorandil on effective reperfusion,and the levels of interleukin-4(IL-4)and soluble intercellular adhesion molecule-1(sICAM-1)after percutaneous coronary intervention(PCI)fo...Aim:The effects of tirofiban combined with nicorandil on effective reperfusion,and the levels of interleukin-4(IL-4)and soluble intercellular adhesion molecule-1(sICAM-1)after percutaneous coronary intervention(PCI)for chronic coronary total occlusion(CTO)were investigated.Method:From January 1,2017,to June 31,2019,a total of 40 patients with CTO receiving PCI in Shandong Qian-foshan Hospital were randomly divided into a control group(treated with single tirofiban)and a cocktail group(treated with nicorandil combined with tirofiban).Effective reperfusion was compared between groups.In addition,differences in coronary serum IL-4 and sICAM-1 levels before and 10 min after the operation were compared between groups,and the incidence rates of adverse reactions were observed.Finally,patient follow-up occurred at 1 month and 6 months,and the total incidence rates of adverse cardiac events in both groups were assessed.Results:The levels of IL-4 and sICAM-1 in the cocktail group significantly decreased after the operation(P<0.05).In addition,after the operation,significantly greater decreases in the IL-4 and sICAM-1 levels were observed in the cocktail group than the control group(P<0.05).The Seattle Angina Scale(SAQ)score of the cocktail group,compared with the control group,showed a significant improvement after vessel opening in the patients with CTO.At the 1-month follow-up,the SAQ score of the cocktail group,compared with the control group,indicated further improvements in terms of angina attack frequency.No significant differences were observed in the incidence rates of adverse reactions between groups(P>0.05).Conclusion:The treatment of patients with CTO undergoing PCI with nicorandil and tirofiban alleviated the inflam-matory response,improved the SAQ scores,and decreased the occurrence of angina pectoris in patients.Moreover,this treatment is safe and reliable,and has important clinical significance.展开更多
背景:随着无牙颌修复需求增加,“All-on-4”技术被广泛应用。种植体与天然牙的载荷传递方式不同,三维有限元分析可研究功能载荷作用下种植体及周围骨组织的应力分布,并在此基础上为寻找适合的种植体材料、优化种植体的几何结构、设计临...背景:随着无牙颌修复需求增加,“All-on-4”技术被广泛应用。种植体与天然牙的载荷传递方式不同,三维有限元分析可研究功能载荷作用下种植体及周围骨组织的应力分布,并在此基础上为寻找适合的种植体材料、优化种植体的几何结构、设计临床手术方案提供了研究方法。目的:对三维有限元分析法在“All-on-4”技术方面的相关研究作一综述。方法:检索中国知网和PubMed数据库2003-2023年相关文献,英文检索词为“Finite Element Method,All-on-4,edentulous,Biomechanics”,中文检索词为“有限元,All-on-4,无牙颌,生物力学”,根据纳入排除标准筛选符合标准的文献,最终纳入65篇文献进行综述。结果与结论:①对水平骨量不足的情况,研究者们可以选择应用窄直径种植体,但需要注意悬臂的存在对应力分布的影响,降低失败的风险。②“All-on-4”概念通过倾斜远中种植体的方法,减少骨的应力分布,但在不同的颌骨类型中,远中种植体倾斜的理想角度还需要进一步的研究。③悬臂的存在会增加种植失败的风险,将悬臂长度/AP距(CL/AP)的比值控制在0.9时,有助于减少机械并发症的发生。④用弹性模量较低的材料制作支架时,支架自身的应力较小,但会增加种植体、中央螺丝、基台及种植体周围骨组织的应力,相反使用弹性模量较大的材料,会降低修复体组件和种植体周围骨组织的应力,但支架本身的应力较高。⑤“All-on-4”概念可以实现较好的力学平衡,但需结合患者自身的具体情况制定一个长期有效的治疗方案。⑥合理的咬合设计是影响种植治疗成功的关键,尖牙引导牙合和组牙功能牙合在修复体的寿命方面无差异。然而,影响咬合设计的原因有很多,未来还需要进一步的体外实验以及大量临床研究来探索“All-on-4”理想的咬合设计。展开更多
Modified constraint-induced movement therapy is an effective treatment for neurological and motor impairments in patients with stroke by increasing the use of their affected limb and limiting the contralateral limb.Ho...Modified constraint-induced movement therapy is an effective treatment for neurological and motor impairments in patients with stroke by increasing the use of their affected limb and limiting the contralateral limb.However,the molecular mechanism underlying its efficacy remains unclear.In this study,a middle cerebral artery occlusion(MCAO)rat model was produced by the suture method.Rats received modified constraint-induced movement therapy 1 hour a day for 14 consecutive days,starting from the 7^th day after middle cerebral artery occlusion.Day 1 of treatment lasted for 10 minutes at 2r/min,day 2 for 20 minutes at 2 r/min,and from day 3 onward for 20 minutes at 4 r/min.CatWalk gait analysis,adhesive removal test,and Y-maze test were used to investigate motor function,sensory function as well as cognitive function in rodent animals from the 1st day before MCAO to the 21^st day after MCAO.On the 21^st day after MCAO,the neurotransmitter receptor-related genes from both contralateral and ipsilateral hippocampi were tested by micro-array and then verified by western blot assay.The glutamate related receptor was shown by transmission electron microscopy and the glutamate content was determined by high-performance liquid chromatography.The results of behavior tests showed that modified constraint-induced movement therapy promoted motor and sensory functional recovery in the middle cerebral artery-occluded rats,but had no effect on cognitive function.The modified constraint-induced movement therapy upregulated the expression of glutamate ionotropic receptor AMPA type subunit 3(Gria3)in the hippocampus and downregulated the expression of the beta3-adrenergic receptor gene Adrb3 and arginine vasopressin receptor 1 A,Avprla in the middle cerebral artery-occluded rats.In the ipsilateral hippocampus,only Adra2 a was downregulated,and there was no significant change in Gria3.Transmission electron microscopy revealed a denser distribution the more distribution of postsynaptic glutamate receptor 2/3,which is an a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor,within 240 nm of the postsynaptic density in the contralateral cornu ammonis 3 region.The size and distribution of the synaptic vesicles within 100 nm of the presynaptic active zone were unchanged.Western blot analysis showed that modified constraint-induced movement therapy also increased the expression of glutamate receptor 2/3 and brain-derived neurotrophic factor in the hippocampus of rats with middle cerebral artery occlusion,but had no effect on Synapsin I levels.Besides,we also found modified constraint-induced movement therapy effectively reduced glutamate content in the contralateral hippocampus.This study demonstrated that modified constraint-induced movement therapy is an effective rehabilitation therapy in middle cerebral artery-occluded rats,and suggests that these positive effects occur via the upregulation of the postsynaptic membrane a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor expression.This study was approved by the Institutional Animal Care and Use Committee of Fudan University,China(approval No.201802173 S)on March 3,2018.展开更多
In vivo imaging of cerebral ischemia/reperfusion injury remains an important challenge.We injected porous Ag/Au@SiO_(2) bimetallic hollow nanoshells carrying anti-tropomyosin 4 as a molecular probe into mice with cere...In vivo imaging of cerebral ischemia/reperfusion injury remains an important challenge.We injected porous Ag/Au@SiO_(2) bimetallic hollow nanoshells carrying anti-tropomyosin 4 as a molecular probe into mice with cerebral ischemia/reperfusion injury and observed microvascular changes in the brain using photoacoustic imaging with ultrasonography.At each measured time point,the total photoacoustic signal was significantly higher on the affected side than on the healthy side.Twelve hours after reperfusion,cerebral perfusion on the affected side increased,cerebrovascular injury worsened,and anti-tropomyosin 4 expression increased.Twenty-four hours after reperfusion and later,perfusion on the affected side declined slowly and stabilized after 1 week;brain injury was also alleviated.Histopathological and immunohistochemical examinations confirmed the brain injury tissue changes.The nanoshell molecular probe carrying anti-tropomyosin 4 has potential for use in early diagnosis of cerebral ischemia/reperfusion injury and evaluating its progression.展开更多
The present study investigated the effects of catalpol, the main constituent of the Chinese herb Rehmannia root, on neurons following brain ischemia, A rat model of focal permanent brain ischemia was established using...The present study investigated the effects of catalpol, the main constituent of the Chinese herb Rehmannia root, on neurons following brain ischemia, A rat model of focal permanent brain ischemia was established using electrocoagulation, The rats were intrapedtoneally injected with catalpol, at a dose of 5 mg/kg, daily for 1 week, Results showed that the number of neuronal synapses in the motor cortex and growth associated protein 43 expression were increased following catalpol treatment, indicating that catalpol might contribute to neuroplasticity and ameliorate functional neurological deficits induced by cerebral ischemia.展开更多
Aquaporin-4 regulates water molecule channels and is important in tissue regulation and water transportation in the brain. Upregulation of aquaporin-4 expression is closely related to cellular edema after early cerebr...Aquaporin-4 regulates water molecule channels and is important in tissue regulation and water transportation in the brain. Upregulation of aquaporin-4 expression is closely related to cellular edema after early cerebral infarction. Cellular edema and aquaporin-4 expression can be determined by measuring cerebral infarct area and apparent diffusion coefficient using diffusion-weighted imaging（DWI）. We examined the effects of silencing aquaporin-4 on cerebral infarction. Rat models of cerebral infarction were established by occlusion of the right middle cerebral artery and si RNA-aquaporin-4 was immediately injected via the right basal ganglia. In control animals, the area of high signal intensity and relative apparent diffusion coefficient value on T2-weighted imaging（T2WI） and DWI gradually increased within 0.5–6 hours after cerebral infarction. After aquaporin-4 gene silencing, the area of high signal intensity on T2 WI and DWI reduced, relative apparent diffusion coefficient value was increased, and cellular edema was obviously alleviated. At 6 hours after cerebral infarction, the apparent diffusion coefficient value was similar between treatment and model groups, but angioedema was still obvious in the treatment group. These results indicate that aquaporin-4 gene silencing can effectively relieve cellular edema after early cerebral infarction; and when conducted accurately and on time, the diffusion coefficient value and the area of high signal intensity on T2 WI and DWI can reflect therapeutic effects of aquaporin-4 gene silencing on cellular edema.展开更多
This manuscript reviews the function and fundamental characteristics of the neurotrophins and their receptors to introduce the reader to the differential effects exhibited by the neurotrophins;brain-derived neurotroph...This manuscript reviews the function and fundamental characteristics of the neurotrophins and their receptors to introduce the reader to the differential effects exhibited by the neurotrophins;brain-derived neurotrophic factor and neurotrophin 4/5 when acted together after sequential presentation.The neurotrophin 4/5 exhibits an inhibitory action on the modulatory effect of brain-derived neurotrophic factor in corticostriatal synapses when they are administered sequentially(brain-derived neurotrophic factor to neurotrophin 4/5).This inhibitory effect has not been previously documented and is relevant for these neurotrophins as both of them stimulate the TrkB receptor.The additive effect of these neurotrophins is also discussed and occurs when neurotrophin 4/5 exposure is followed by brain-derived neurotrophic factor in a mouse model of striatal degeneration.Occlusive and additive effects of both neurotrophins are accompanied by changes in the expression of the TrkB receptor isoforms,specifically TrkB-T1 and TrkB-FL,as well as differences in phosphorylation levels of the TrkB receptor.The results of the experiments described raise several questions to inquire about the role that TrkB-T1 receptor plays in striatal physiology,as well as the functional relevance of the interaction of brain-derived neurotrophic factor and neurotrophin 4/5 in the brain and more specifically at the striatal circuits in normal as well as pathological conditions.展开更多
文摘目的:骨形态发生蛋白-4(bone morphogenentic protein-4,BMP4)在动脉粥样硬化(atherosclerosis,AS)的病理过程中具有重要调节作用,但相关的临床研究较少。本研究拟观察以AS为主要病理特点的动脉阻塞性疾病(arterial occlusive disease,ACD)患者血浆BMP4的表达情况,并分析血浆中BMP4与炎症因子和血管损伤标志物之间的相关性。方法:共招募38名诊断为ACD的患者(ACD组)和38名体检志愿者(对照组),抽取ACD组患者术前和对照组体检时的静脉血,比较2组血常规指标的差异。采用酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测血浆中BMP4、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素(interleukin,IL)-1β、IL-10及血管内皮钙黏蛋白(vascular endothelial cadherin,VE-cadherin)的表达变化,并进一步分析BMP4与以上各指标之间的相关性。结果:与对照组相比,ACD组患者血常规结果表现为中性粒细胞-淋巴细胞比值[neutrophil to lymphocyte ratio,NLR;1.63(1.26,1.91)vs 3.43(2.16,6.61)]和血小板-淋巴细胞比值[platelet to lymphocyte ratio,PLR;6.37(5.26,7.74)vs 15.79(7.97,20.53)]升高、淋巴细胞-单核细胞比值[lymphocyte to monocyte ratio,LMR;5.67(4.41,7.14)vs3.43(2.07,3.74)]下降(均P<0.05);ACD组患者血浆BMP4[581.26(389.85,735.64)pg/mL vs 653.97(510.95,890.43)pg/mL]、TNF-α[254.16(182.96,340.70)pg/mLvs293.29(238.90,383.44)pg/mL]及内皮标志物VE-cadherin[1.54(1.08,2.13)ng/mL vs 1.85(1.30,2.54)ng/mL]的水平均显著升高,而抗炎因子IL-10的水平显著下降[175.89(118.39,219.25)pg/mLvs135.92(95.80,178.04)pg/mL](均P<0.05)。2组间促炎因子IL-1β的差异无统计学意义[300.39(205.39,403.56)pg/mL vs 378.46(243.20,448.69)pg/mL;P=0.09]。相关分析结果表明:血浆BMP4水平与促炎因子IL-1β(r=0.35)、TNF-α(r=0.31)以及内皮标志物VE-cadherin(r=0.47)呈正相关,与抗炎因子IL-10呈负相关(r=-0.37;均P<0.01)。结论:ACD患者血浆BMP4的水平升高,且与患者的炎症水平和血管损伤程度具有相关性。
基金supported by research grants from the Natural Science Foundation of Shandong Province[grant number ZR2017BH114],the National Natural Science Foundation of China[grant number 81700334],and Jinan Science and Technology Plan Project[grant number 201805058].
文摘Aim:The effects of tirofiban combined with nicorandil on effective reperfusion,and the levels of interleukin-4(IL-4)and soluble intercellular adhesion molecule-1(sICAM-1)after percutaneous coronary intervention(PCI)for chronic coronary total occlusion(CTO)were investigated.Method:From January 1,2017,to June 31,2019,a total of 40 patients with CTO receiving PCI in Shandong Qian-foshan Hospital were randomly divided into a control group(treated with single tirofiban)and a cocktail group(treated with nicorandil combined with tirofiban).Effective reperfusion was compared between groups.In addition,differences in coronary serum IL-4 and sICAM-1 levels before and 10 min after the operation were compared between groups,and the incidence rates of adverse reactions were observed.Finally,patient follow-up occurred at 1 month and 6 months,and the total incidence rates of adverse cardiac events in both groups were assessed.Results:The levels of IL-4 and sICAM-1 in the cocktail group significantly decreased after the operation(P<0.05).In addition,after the operation,significantly greater decreases in the IL-4 and sICAM-1 levels were observed in the cocktail group than the control group(P<0.05).The Seattle Angina Scale(SAQ)score of the cocktail group,compared with the control group,showed a significant improvement after vessel opening in the patients with CTO.At the 1-month follow-up,the SAQ score of the cocktail group,compared with the control group,indicated further improvements in terms of angina attack frequency.No significant differences were observed in the incidence rates of adverse reactions between groups(P>0.05).Conclusion:The treatment of patients with CTO undergoing PCI with nicorandil and tirofiban alleviated the inflam-matory response,improved the SAQ scores,and decreased the occurrence of angina pectoris in patients.Moreover,this treatment is safe and reliable,and has important clinical significance.
文摘背景:随着无牙颌修复需求增加,“All-on-4”技术被广泛应用。种植体与天然牙的载荷传递方式不同,三维有限元分析可研究功能载荷作用下种植体及周围骨组织的应力分布,并在此基础上为寻找适合的种植体材料、优化种植体的几何结构、设计临床手术方案提供了研究方法。目的:对三维有限元分析法在“All-on-4”技术方面的相关研究作一综述。方法:检索中国知网和PubMed数据库2003-2023年相关文献,英文检索词为“Finite Element Method,All-on-4,edentulous,Biomechanics”,中文检索词为“有限元,All-on-4,无牙颌,生物力学”,根据纳入排除标准筛选符合标准的文献,最终纳入65篇文献进行综述。结果与结论:①对水平骨量不足的情况,研究者们可以选择应用窄直径种植体,但需要注意悬臂的存在对应力分布的影响,降低失败的风险。②“All-on-4”概念通过倾斜远中种植体的方法,减少骨的应力分布,但在不同的颌骨类型中,远中种植体倾斜的理想角度还需要进一步的研究。③悬臂的存在会增加种植失败的风险,将悬臂长度/AP距(CL/AP)的比值控制在0.9时,有助于减少机械并发症的发生。④用弹性模量较低的材料制作支架时,支架自身的应力较小,但会增加种植体、中央螺丝、基台及种植体周围骨组织的应力,相反使用弹性模量较大的材料,会降低修复体组件和种植体周围骨组织的应力,但支架本身的应力较高。⑤“All-on-4”概念可以实现较好的力学平衡,但需结合患者自身的具体情况制定一个长期有效的治疗方案。⑥合理的咬合设计是影响种植治疗成功的关键,尖牙引导牙合和组牙功能牙合在修复体的寿命方面无差异。然而,影响咬合设计的原因有很多,未来还需要进一步的体外实验以及大量临床研究来探索“All-on-4”理想的咬合设计。
基金supported by the National Natural Science Foundation of China,No.81871841(to YLB) and No.81772453(to DSX)
文摘Modified constraint-induced movement therapy is an effective treatment for neurological and motor impairments in patients with stroke by increasing the use of their affected limb and limiting the contralateral limb.However,the molecular mechanism underlying its efficacy remains unclear.In this study,a middle cerebral artery occlusion(MCAO)rat model was produced by the suture method.Rats received modified constraint-induced movement therapy 1 hour a day for 14 consecutive days,starting from the 7^th day after middle cerebral artery occlusion.Day 1 of treatment lasted for 10 minutes at 2r/min,day 2 for 20 minutes at 2 r/min,and from day 3 onward for 20 minutes at 4 r/min.CatWalk gait analysis,adhesive removal test,and Y-maze test were used to investigate motor function,sensory function as well as cognitive function in rodent animals from the 1st day before MCAO to the 21^st day after MCAO.On the 21^st day after MCAO,the neurotransmitter receptor-related genes from both contralateral and ipsilateral hippocampi were tested by micro-array and then verified by western blot assay.The glutamate related receptor was shown by transmission electron microscopy and the glutamate content was determined by high-performance liquid chromatography.The results of behavior tests showed that modified constraint-induced movement therapy promoted motor and sensory functional recovery in the middle cerebral artery-occluded rats,but had no effect on cognitive function.The modified constraint-induced movement therapy upregulated the expression of glutamate ionotropic receptor AMPA type subunit 3(Gria3)in the hippocampus and downregulated the expression of the beta3-adrenergic receptor gene Adrb3 and arginine vasopressin receptor 1 A,Avprla in the middle cerebral artery-occluded rats.In the ipsilateral hippocampus,only Adra2 a was downregulated,and there was no significant change in Gria3.Transmission electron microscopy revealed a denser distribution the more distribution of postsynaptic glutamate receptor 2/3,which is an a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor,within 240 nm of the postsynaptic density in the contralateral cornu ammonis 3 region.The size and distribution of the synaptic vesicles within 100 nm of the presynaptic active zone were unchanged.Western blot analysis showed that modified constraint-induced movement therapy also increased the expression of glutamate receptor 2/3 and brain-derived neurotrophic factor in the hippocampus of rats with middle cerebral artery occlusion,but had no effect on Synapsin I levels.Besides,we also found modified constraint-induced movement therapy effectively reduced glutamate content in the contralateral hippocampus.This study demonstrated that modified constraint-induced movement therapy is an effective rehabilitation therapy in middle cerebral artery-occluded rats,and suggests that these positive effects occur via the upregulation of the postsynaptic membrane a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor expression.This study was approved by the Institutional Animal Care and Use Committee of Fudan University,China(approval No.201802173 S)on March 3,2018.
基金supported by the National Natural Science Foundation of China,No.81730050(to WH).
文摘In vivo imaging of cerebral ischemia/reperfusion injury remains an important challenge.We injected porous Ag/Au@SiO_(2) bimetallic hollow nanoshells carrying anti-tropomyosin 4 as a molecular probe into mice with cerebral ischemia/reperfusion injury and observed microvascular changes in the brain using photoacoustic imaging with ultrasonography.At each measured time point,the total photoacoustic signal was significantly higher on the affected side than on the healthy side.Twelve hours after reperfusion,cerebral perfusion on the affected side increased,cerebrovascular injury worsened,and anti-tropomyosin 4 expression increased.Twenty-four hours after reperfusion and later,perfusion on the affected side declined slowly and stabilized after 1 week;brain injury was also alleviated.Histopathological and immunohistochemical examinations confirmed the brain injury tissue changes.The nanoshell molecular probe carrying anti-tropomyosin 4 has potential for use in early diagnosis of cerebral ischemia/reperfusion injury and evaluating its progression.
基金the National Natural Science Foundation of China, No. 81073084the Fundamental Research Funds for the Central Universities, No.XDJK2009C081+1 种基金the Natural Science Foundation Project of CQ CSTC, No.2010BB5127Science and Technology Innovative Capacity Construction Program of Chongqing(CSTC) No.2009CB1010
文摘The present study investigated the effects of catalpol, the main constituent of the Chinese herb Rehmannia root, on neurons following brain ischemia, A rat model of focal permanent brain ischemia was established using electrocoagulation, The rats were intrapedtoneally injected with catalpol, at a dose of 5 mg/kg, daily for 1 week, Results showed that the number of neuronal synapses in the motor cortex and growth associated protein 43 expression were increased following catalpol treatment, indicating that catalpol might contribute to neuroplasticity and ameliorate functional neurological deficits induced by cerebral ischemia.
基金supported by the National Natural Science Foundation of China,No.30960399a grant from Hainan Provincial International Cooperation Project of China,No.Qiongke(2012)65a grant from Hainan Provincial Health Department Project of China,No.2011-SWK-10-136/Qiongwei2011-65
文摘Aquaporin-4 regulates water molecule channels and is important in tissue regulation and water transportation in the brain. Upregulation of aquaporin-4 expression is closely related to cellular edema after early cerebral infarction. Cellular edema and aquaporin-4 expression can be determined by measuring cerebral infarct area and apparent diffusion coefficient using diffusion-weighted imaging（DWI）. We examined the effects of silencing aquaporin-4 on cerebral infarction. Rat models of cerebral infarction were established by occlusion of the right middle cerebral artery and si RNA-aquaporin-4 was immediately injected via the right basal ganglia. In control animals, the area of high signal intensity and relative apparent diffusion coefficient value on T2-weighted imaging（T2WI） and DWI gradually increased within 0.5–6 hours after cerebral infarction. After aquaporin-4 gene silencing, the area of high signal intensity on T2 WI and DWI reduced, relative apparent diffusion coefficient value was increased, and cellular edema was obviously alleviated. At 6 hours after cerebral infarction, the apparent diffusion coefficient value was similar between treatment and model groups, but angioedema was still obvious in the treatment group. These results indicate that aquaporin-4 gene silencing can effectively relieve cellular edema after early cerebral infarction; and when conducted accurately and on time, the diffusion coefficient value and the area of high signal intensity on T2 WI and DWI can reflect therapeutic effects of aquaporin-4 gene silencing on cellular edema.
基金supported by Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica Grants No.216515 and IN 211718。
文摘This manuscript reviews the function and fundamental characteristics of the neurotrophins and their receptors to introduce the reader to the differential effects exhibited by the neurotrophins;brain-derived neurotrophic factor and neurotrophin 4/5 when acted together after sequential presentation.The neurotrophin 4/5 exhibits an inhibitory action on the modulatory effect of brain-derived neurotrophic factor in corticostriatal synapses when they are administered sequentially(brain-derived neurotrophic factor to neurotrophin 4/5).This inhibitory effect has not been previously documented and is relevant for these neurotrophins as both of them stimulate the TrkB receptor.The additive effect of these neurotrophins is also discussed and occurs when neurotrophin 4/5 exposure is followed by brain-derived neurotrophic factor in a mouse model of striatal degeneration.Occlusive and additive effects of both neurotrophins are accompanied by changes in the expression of the TrkB receptor isoforms,specifically TrkB-T1 and TrkB-FL,as well as differences in phosphorylation levels of the TrkB receptor.The results of the experiments described raise several questions to inquire about the role that TrkB-T1 receptor plays in striatal physiology,as well as the functional relevance of the interaction of brain-derived neurotrophic factor and neurotrophin 4/5 in the brain and more specifically at the striatal circuits in normal as well as pathological conditions.
