Imaging technologies are utilized to study the brain morphology and the functions of rat models of Parkinson disease （PD）. Magnetic resonance imaging （MRI） and magnetic resonance angiography （MRA） are used to ob...Imaging technologies are utilized to study the brain morphology and the functions of rat models of Parkinson disease （PD）. Magnetic resonance imaging （MRI） and magnetic resonance angiography （MRA） are used to obtain morphological imaging data. Functional imaging data, such as the spectrum and blood flow changes are obtained by proton magnetic resonance spectroscopy （1H-MRS） and CT perfusion （CTP）. Results show that PD rat models have no characteristic morphological imaging abnormalities, but exist regional cerebral blood flow （CBF） reductions and spectral changes in the striatum.展开更多
Uric acid(UA)is a naturally antioxidant that is strongly associated with the development and progression of Parkinson's disease(PD).The purine diet is an important exogenous pathway that modulates blood UA levels....Uric acid(UA)is a naturally antioxidant that is strongly associated with the development and progression of Parkinson's disease(PD).The purine diet is an important exogenous pathway that modulates blood UA levels.Deep brain stimulation(DBS)is an important tool for PD treatment.This study aimed to explore the effects of preoperative purine diet on the prognosis of patients with PD after DBS.Sixty-four patients with PD who underwent DBS were included in this study,and their clinical data,blood UA levels,and daily purine intake.Patients were followed up for improvement 1 year after surgery.We found that patient higher purine intake was strongly associated with the rate of improvement after DBS and was a protective factor for patient prognosis.Daily purine intake from meat and seafood was significantly higher in the responsive patients than in the lessresponsive patients.Mediation analysis showed that UA mediated 78%of the effect of purine intake on motor symptom improvement after DBS.In summary,we observed that purine intake is strongly associated with the rate of improvement in motor symptoms after subthalamic nucleus-DBS in patients with PD.This study provides a reference for preoperative diet planning in patients with PD undergoing DBS.展开更多
Parkinson's disease(PD)is one of the most common neurodegenerative diseases.The loss of dopaminergic(DAergic)neurons in the substantia nigra and the decrease of dopamine(DA)levels accelerate the process of PD.L-Er...Parkinson's disease(PD)is one of the most common neurodegenerative diseases.The loss of dopaminergic(DAergic)neurons in the substantia nigra and the decrease of dopamine(DA)levels accelerate the process of PD.L-Ergothioneine(EGT)is a natural antioxidant derived from microorganisms,especially in edible mushrooms.EGT can penetrate blood-brain barrier and its levels are significantly decreased in the plasma of PD patients.Therefore,we speculated that EGT could ameliorate PD,and determined its effect on PD development by using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mouse models and neurotoxin 1-methyl-4-phenylpyridinium(MPP^(+))-induced cell models.Our results show that EGT alleviated MPTP-induced behavioral dysfunction in mice.Mechanistically,we innovatively revealed that EGT was a key regulator of DJ-1.EGT restored DA levels by activating the DJ-1-nuclear receptor-related factor 1(Nurr1)axis.Furthermore,it reduced reactive oxygen species(ROS)levels by regulating the DJ-1-nuclear factor erythroid 2-related factor 2(Nrf2)pathway,which inhibited oxidative stress-induced DAergic neuronal apoptosis.Combined treatment with DJ-1-si RNA transfection revealed that blocking DJ-1 reversed EGT upregulated Nurr1 and Nrf2 expression in the nucleus,which significantly decreased the benefits of EGT.Taken together,our study suggests that EGT can ameliorate PD and be considered as a strategy for PD treatment.展开更多
Parkinson’s disease (PD) is a slowly progressive neurodegenerative disorder with motor and non-motorsigns, which begins long before the diagnosis can be made. Pharmacotherapy with dopaminergic drugsis the mainstay of...Parkinson’s disease (PD) is a slowly progressive neurodegenerative disorder with motor and non-motorsigns, which begins long before the diagnosis can be made. Pharmacotherapy with dopaminergic drugsis the mainstay of PD therapy. There is no currently available cure or disease-modifying treatment. Dietand various foods have been proposed as possible risk factors for PD. Nutritional supplementation withomega-3 fatty acids, vitamin D, B vitamins, and coenzyme Q may have potential in the management ofPD. In addition, several strategies could possibly lead to the development of medical foods in PD. Forexample, ketogenic diets may have effects complementary to pharmacotherapy. Gut microbial dysbiosisand altered microbial metabolites found in PD may lead to chronic low-grade inflammation in gut andbrain. Interventions targeting gut microbiota, such as the supplementation of probiotics, may providenovel approaches to PD in regard to both symptomatic treatment and disease modification. High qualityrandomized controlled trials need to be conducted in order to evaluate whether these food-basedstrategies have symptomatic efficacy or the potential to delay the progression of PD.展开更多
Parkinson’s disease(PD),a neurodegenerative disease that shows a high incidence in older individuals,is becoming increasingly prevalent.Unfortunately,there is no clinical cure for PD,and novel anti-PD drugs are there...Parkinson’s disease(PD),a neurodegenerative disease that shows a high incidence in older individuals,is becoming increasingly prevalent.Unfortunately,there is no clinical cure for PD,and novel anti-PD drugs are therefore urgently required.However,the selective permeability of the blood–brain barrier(BBB)poses a huge challenge in the development of such drugs.Fortunately,through strategies based on the physiological characteristics of the BBB and other modifications,including enhancement of BBB permeability,nanotechnology can offer a solution to this problem and facilitate drug delivery across the BBB.Although nanomaterials are often used as carriers for PD treatment,their biological activity is ignored.Several studies in recent years have shown that nanomaterials can improve PD symptoms via their own nano-bio effects.In this review,we first summarize the physiological features of the BBB and then discuss the design of appropriate brain-targeted delivery nanoplatforms for PD treatment.Subsequently,we highlight the emerging strategies for crossing the BBB and the development of novel nanomaterials with anti-PD nano-biological effects.Finally,we discuss the current challenges in nanomaterial-based PD treatment and the future trends in this field.Our review emphasizes the clinical value of nanotechnology in PD treatment based on recent patents and could guide researchers working in this area in the future.展开更多
This paper provides an adaptive closed-loop strategy for suppressing the pathological oscillations of the basal ganglia based on a variable universe fuzzy algorithm.The pathological basal ganglia oscillations in the t...This paper provides an adaptive closed-loop strategy for suppressing the pathological oscillations of the basal ganglia based on a variable universe fuzzy algorithm.The pathological basal ganglia oscillations in the theta(4-9 Hz)and beta(12-35 Hz)frequency bands have been demonstrated to be associated with the tremor and rigidity/bradykinesia symptoms in Parkinson’s disease(PD).Although the clinical application of open-loop deep brain stimulation(DBS)is effective,the stimulation waveform with the fixed parameters cannot be self-adjusted as the disease progresses,and thus the stimulation effects go poor.To deal with this difficult problem,a variable universe fuzzy closed-loop strategy is proposed to modulate different PD states.We establish a cortico-basal ganglia-thalamocortical network model to simulate pathological oscillations and test the control effect.The results suggest that the proposed closed-loop control strategy can accommodate the variation of brain states and symptoms,which may become an alternative method to administrate the symptoms in PD.展开更多
Parkinson’s disease(PD)is a common neurodegenerative disorder with no cure.Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity.The present study aimed to explore the neuroprotect...Parkinson’s disease(PD)is a common neurodegenerative disorder with no cure.Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity.The present study aimed to explore the neuroprotective effects of total flavonoids extracted from A.membranaceus(TFA)and their protective mechanisms.TFA offered neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)in the mouse model of Parkinsonism,by improving behavior performance in the gait analysis and pole test,and inhibiting the decline of tyrosine hydroxylase(TH)positive neurons and TH protein expression in substantia nigra of mice.TFA also prevented 1-methyl-4-phenylpyridinium(MPP+)induced neurotoxicity in SHSY5Y cells,by increasing GSH and GSH/GSSG ratio,and reducing reactive oxygen species.In addition,the neuroprotective effects of TFA were associated with its ability to restore MPTP/MPP+induced downregulation of SLC7A11 and glutathione peroxidase 4(GPX-4).In conclusion,we demonstrated that TFA exerted significant neuroprotection against MPTP/MPP+induced neurodegeneration by inhibiting ferroptosis through the regulation of SLC7A11/GPX-4 axis,suggesting the use of TFA as a possible food supplement in the prevention of PD.展开更多
Objective To explore the efficacy of target positioning by preoperative CT/MRI image fusion technique in deep brain stimulation.Methods We retrospectively analyzed the clinical data and images of 79 cases(68 with Park...Objective To explore the efficacy of target positioning by preoperative CT/MRI image fusion technique in deep brain stimulation.Methods We retrospectively analyzed the clinical data and images of 79 cases(68 with Parkinson's disease,11 with dystonia) who received preoperative CT/MRI image fusion in target positioning of subthalamic nucleus in deep brain stimulation.Deviation of implanted electrodes from the target nucleus of each patient were measured.Neurological evaluations of each patient before and after the treatment were performed and compared.Complications of the positioning and treatment were recorded.Results The mean deviations of the electrodes implanted on X,Y,and Z axis were 0.5 mm,0.6 mm,and 0.6 mm,respectively.Postoperative neurologic evaluations scores of unified Parkinson's disease rating scale(UPDRS) for Parkinson's disease and Burke-Fahn-Marsden Dystonia Rating Scale(BFMDRS) for dystonia patients improved significantly compared to the preoperative scores(P<0.001); Complications occurred in 10.1%(8/79) patients,and main side effects were dysarthria and diplopia.Conclusion Target positioning by preoperative CT/MRI image fusion technique in deep brain stimulation has high accuracy and good clinical outcomes.展开更多
基金Supported by the National Natural Science Foundation of China (30671997)~~
文摘Imaging technologies are utilized to study the brain morphology and the functions of rat models of Parkinson disease （PD）. Magnetic resonance imaging （MRI） and magnetic resonance angiography （MRA） are used to obtain morphological imaging data. Functional imaging data, such as the spectrum and blood flow changes are obtained by proton magnetic resonance spectroscopy （1H-MRS） and CT perfusion （CTP）. Results show that PD rat models have no characteristic morphological imaging abnormalities, but exist regional cerebral blood flow （CBF） reductions and spectral changes in the striatum.
文摘Uric acid(UA)is a naturally antioxidant that is strongly associated with the development and progression of Parkinson's disease(PD).The purine diet is an important exogenous pathway that modulates blood UA levels.Deep brain stimulation(DBS)is an important tool for PD treatment.This study aimed to explore the effects of preoperative purine diet on the prognosis of patients with PD after DBS.Sixty-four patients with PD who underwent DBS were included in this study,and their clinical data,blood UA levels,and daily purine intake.Patients were followed up for improvement 1 year after surgery.We found that patient higher purine intake was strongly associated with the rate of improvement after DBS and was a protective factor for patient prognosis.Daily purine intake from meat and seafood was significantly higher in the responsive patients than in the lessresponsive patients.Mediation analysis showed that UA mediated 78%of the effect of purine intake on motor symptom improvement after DBS.In summary,we observed that purine intake is strongly associated with the rate of improvement in motor symptoms after subthalamic nucleus-DBS in patients with PD.This study provides a reference for preoperative diet planning in patients with PD undergoing DBS.
基金supported by the National Natural Science Foundation of China(U22A20272,82173807,82170497)。
文摘Parkinson's disease(PD)is one of the most common neurodegenerative diseases.The loss of dopaminergic(DAergic)neurons in the substantia nigra and the decrease of dopamine(DA)levels accelerate the process of PD.L-Ergothioneine(EGT)is a natural antioxidant derived from microorganisms,especially in edible mushrooms.EGT can penetrate blood-brain barrier and its levels are significantly decreased in the plasma of PD patients.Therefore,we speculated that EGT could ameliorate PD,and determined its effect on PD development by using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mouse models and neurotoxin 1-methyl-4-phenylpyridinium(MPP^(+))-induced cell models.Our results show that EGT alleviated MPTP-induced behavioral dysfunction in mice.Mechanistically,we innovatively revealed that EGT was a key regulator of DJ-1.EGT restored DA levels by activating the DJ-1-nuclear receptor-related factor 1(Nurr1)axis.Furthermore,it reduced reactive oxygen species(ROS)levels by regulating the DJ-1-nuclear factor erythroid 2-related factor 2(Nrf2)pathway,which inhibited oxidative stress-induced DAergic neuronal apoptosis.Combined treatment with DJ-1-si RNA transfection revealed that blocking DJ-1 reversed EGT upregulated Nurr1 and Nrf2 expression in the nucleus,which significantly decreased the benefits of EGT.Taken together,our study suggests that EGT can ameliorate PD and be considered as a strategy for PD treatment.
文摘Parkinson’s disease (PD) is a slowly progressive neurodegenerative disorder with motor and non-motorsigns, which begins long before the diagnosis can be made. Pharmacotherapy with dopaminergic drugsis the mainstay of PD therapy. There is no currently available cure or disease-modifying treatment. Dietand various foods have been proposed as possible risk factors for PD. Nutritional supplementation withomega-3 fatty acids, vitamin D, B vitamins, and coenzyme Q may have potential in the management ofPD. In addition, several strategies could possibly lead to the development of medical foods in PD. Forexample, ketogenic diets may have effects complementary to pharmacotherapy. Gut microbial dysbiosisand altered microbial metabolites found in PD may lead to chronic low-grade inflammation in gut andbrain. Interventions targeting gut microbiota, such as the supplementation of probiotics, may providenovel approaches to PD in regard to both symptomatic treatment and disease modification. High qualityrandomized controlled trials need to be conducted in order to evaluate whether these food-basedstrategies have symptomatic efficacy or the potential to delay the progression of PD.
基金This work was financially supported through grants from the Guangdong Basic and Applied Basic Research Foundation(2019B1515120043)National Natural Science Foundation of China(File No.82104354)+2 种基金the Science and Technology Development Fund,Macao SAR(File No.0016/2021/A)and the Open Project of Key Laboratory of Modern Preparation of Traditional Chinese Medicine,Ministry of Education,Jiangxi University of Chinese Medicine(zdsys-202101)Open access funding provided by Shanghai Jiao Tong University
文摘Parkinson’s disease(PD),a neurodegenerative disease that shows a high incidence in older individuals,is becoming increasingly prevalent.Unfortunately,there is no clinical cure for PD,and novel anti-PD drugs are therefore urgently required.However,the selective permeability of the blood–brain barrier(BBB)poses a huge challenge in the development of such drugs.Fortunately,through strategies based on the physiological characteristics of the BBB and other modifications,including enhancement of BBB permeability,nanotechnology can offer a solution to this problem and facilitate drug delivery across the BBB.Although nanomaterials are often used as carriers for PD treatment,their biological activity is ignored.Several studies in recent years have shown that nanomaterials can improve PD symptoms via their own nano-bio effects.In this review,we first summarize the physiological features of the BBB and then discuss the design of appropriate brain-targeted delivery nanoplatforms for PD treatment.Subsequently,we highlight the emerging strategies for crossing the BBB and the development of novel nanomaterials with anti-PD nano-biological effects.Finally,we discuss the current challenges in nanomaterial-based PD treatment and the future trends in this field.Our review emphasizes the clinical value of nanotechnology in PD treatment based on recent patents and could guide researchers working in this area in the future.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.62173241 and 62171312)the Natural Science Foundation of Tianjin,China(Grant Nos.20JCQNJC01160 and 19JCZDJC36500)the financial support provided by Opening Foundation of Key Laboratory of Opto-technology and Intelligent Control(Lanzhou Jiaotong University),Ministry of Education,China(Grant No.KFKT2020-01)
文摘This paper provides an adaptive closed-loop strategy for suppressing the pathological oscillations of the basal ganglia based on a variable universe fuzzy algorithm.The pathological basal ganglia oscillations in the theta(4-9 Hz)and beta(12-35 Hz)frequency bands have been demonstrated to be associated with the tremor and rigidity/bradykinesia symptoms in Parkinson’s disease(PD).Although the clinical application of open-loop deep brain stimulation(DBS)is effective,the stimulation waveform with the fixed parameters cannot be self-adjusted as the disease progresses,and thus the stimulation effects go poor.To deal with this difficult problem,a variable universe fuzzy closed-loop strategy is proposed to modulate different PD states.We establish a cortico-basal ganglia-thalamocortical network model to simulate pathological oscillations and test the control effect.The results suggest that the proposed closed-loop control strategy can accommodate the variation of brain states and symptoms,which may become an alternative method to administrate the symptoms in PD.
文摘Parkinson’s disease(PD)is a common neurodegenerative disorder with no cure.Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity.The present study aimed to explore the neuroprotective effects of total flavonoids extracted from A.membranaceus(TFA)and their protective mechanisms.TFA offered neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)in the mouse model of Parkinsonism,by improving behavior performance in the gait analysis and pole test,and inhibiting the decline of tyrosine hydroxylase(TH)positive neurons and TH protein expression in substantia nigra of mice.TFA also prevented 1-methyl-4-phenylpyridinium(MPP+)induced neurotoxicity in SHSY5Y cells,by increasing GSH and GSH/GSSG ratio,and reducing reactive oxygen species.In addition,the neuroprotective effects of TFA were associated with its ability to restore MPTP/MPP+induced downregulation of SLC7A11 and glutathione peroxidase 4(GPX-4).In conclusion,we demonstrated that TFA exerted significant neuroprotection against MPTP/MPP+induced neurodegeneration by inhibiting ferroptosis through the regulation of SLC7A11/GPX-4 axis,suggesting the use of TFA as a possible food supplement in the prevention of PD.
文摘Objective To explore the efficacy of target positioning by preoperative CT/MRI image fusion technique in deep brain stimulation.Methods We retrospectively analyzed the clinical data and images of 79 cases(68 with Parkinson's disease,11 with dystonia) who received preoperative CT/MRI image fusion in target positioning of subthalamic nucleus in deep brain stimulation.Deviation of implanted electrodes from the target nucleus of each patient were measured.Neurological evaluations of each patient before and after the treatment were performed and compared.Complications of the positioning and treatment were recorded.Results The mean deviations of the electrodes implanted on X,Y,and Z axis were 0.5 mm,0.6 mm,and 0.6 mm,respectively.Postoperative neurologic evaluations scores of unified Parkinson's disease rating scale(UPDRS) for Parkinson's disease and Burke-Fahn-Marsden Dystonia Rating Scale(BFMDRS) for dystonia patients improved significantly compared to the preoperative scores(P<0.001); Complications occurred in 10.1%(8/79) patients,and main side effects were dysarthria and diplopia.Conclusion Target positioning by preoperative CT/MRI image fusion technique in deep brain stimulation has high accuracy and good clinical outcomes.
