scholarly journals Neural Transplantation in Parkinson's Disease

1997 ◽  
Vol 24 (04) ◽  
pp. 292-301 ◽  
Author(s):  
V. Mehta ◽  
J. Spears ◽  
I. Mendez
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Medical Management ◽  
Neurodegenerative Disorder ◽  
Fetal Tissue ◽  
Neural Transplantation ◽  
Current Status ◽  
Neurosurgical Procedures ◽  
Nigrostriatal Pathway

ABSTRACT:Parkinson's disease is a neurodegenerative disorder that affects about 1% of Canadians between the ages of fifty and seventy. The medical management for these patients consists of drug therapy that is initially effective but has limited long term benefits and does not alter the progressive course of the disease. The recalcitrance of longstanding Parkinson's disease to medical management has prompted the use of alternative surgical therapies. Many neurosurgical procedures have been utilized in order to improve the disabling symptoms these patients harbour. Although most of the current procedures involve making destructive lesions within various basal ganglia nuclei, neural transplantation attempts to reconstitute the normal nigrostriatal pathway and restore striatal dopamine. The initial success of neural transplantation in the rodent and primate parkinsonian models has led to its clinical application in the treatment of parkinsonian patients. Currently, well over one hundred patients throughout the world have been grafted with fetal tissue in an effort to ameliorate their parkinsonian symptoms. Although the results of neural transplantation in clinical trials are promising, a number of issues need to be resolved before this technology can become a standard treatment option. This review focuses on the current status of neural transplantation in Parkinson's disease within the context of other surgical therapies in current use.

Evidence for Early and Regular Physical Therapy and Exercise in Parkinson's Disease

2021 ◽  
Author(s):  
Terry D. Ellis ◽  
Cristina Colón-Semenza ◽  
Tamara R. DeAngelis ◽  
Cathi A. Thomas ◽  
Marie-Hélène Saint Hilaire ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Physical Therapy ◽  
Secondary Prevention ◽  
Medical Management ◽  
Long Term Outcomes ◽  
High Prevalence ◽  
Growing Body ◽  
Prevention Model

AbstractAdvances in medical management of Parkinson's disease (PD) have resulted in living longer with disability. Although disability worsens over the course of the disease, there are signs of disability even in the early stages. Several studies reveal an early decline in gait and balance and a high prevalence of nonmotor signs in the prodromal period that contribute to early disability. There is a growing body of evidence revealing the benefits of physical therapy and exercise to mitigate motor and nonmotor signs while improving physical function and reducing disability. The presence of early disability coupled with the benefits of exercise suggests that physical therapy should be initiated earlier in the disease. In this review, we present the evidence revealing early disability in PD and the effectiveness of physical therapy and exercise, followed by a discussion of a secondary prevention model of rehabilitation to reduce early disability and optimize long-term outcomes.

scholarly journals Impact of Aging on the 6-OHDA-Induced Rat Model of Parkinson’s Disease

2020 ◽  
Vol 21 (10) ◽  
pp. 3459 ◽  
Author(s):  
Sandra Barata-Antunes ◽  
Fábio G. Teixeira ◽  
Bárbara Mendes-Pinheiro ◽  
Ana V. Domingues ◽  
Helena Vilaça-Faria ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Welfare ◽  
Neurodegenerative Disorder ◽  
Negative Impact ◽  
Substantia Nigra Pars Compacta ◽  
Nigrostriatal Pathway ◽  
Aged Rats ◽  
Age Related ◽  
The Impact

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder. The neurodegeneration leading to incapacitating motor abnormalities mainly occurs in the nigrostriatal pathway due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Several animal models have been developed not only to better understand the mechanisms underlying neurodegeneration but also to test the potential of emerging disease-modifying therapies. However, despite aging being the main risk factor for developing idiopathic PD, most of the studies do not use aged animals. Therefore, this study aimed at assessing the effect of aging in the unilateral 6-hydroxydopamine (6-OHDA)-induced animal model of PD. For this, female young adult and aged rats received a unilateral injection of 6-OHDA into the medial forebrain bundle. Subsequently, the impact of aging on 6-OHDA-induced effects on animal welfare, motor performance, and nigrostriatal integrity were assessed. The results showed that aging had a negative impact on animal welfare after surgery. Furthermore, 6-OHDA-induced impairments on skilled motor function were significantly higher in aged rats when compared with their younger counterparts. Nigrostriatal histological analysis further revealed an increased 6-OHDA-induced dopaminergic cell loss in the SNpc of aged animals when compared to young animals. Overall, our results demonstrate a higher susceptibility of aged animals to 6-OHDA toxic insult.

scholarly journals Therapeutic Potential of Repeated Intravenous Transplantation of Human Adipose-Derived Stem Cells in Subchronic MPTP-Induced Parkinson’s Disease Mouse Model

2020 ◽  
Vol 21 (21) ◽  
pp. 8129
Author(s):  
Hyunjun Park ◽  
Keun-A Chang
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Neurodegenerative Disease ◽  
Neurotrophic Factor ◽  
Dopaminergic Neurons ◽  
Therapeutic Potential ◽  
Adipose Derived Stem Cells ◽  
Nigrostriatal Pathway

Parkinson’s disease (PD) is the second most common neurodegenerative disease, which is clinically and pathologically characterized by motor dysfunction and the loss of dopaminergic neurons in the substantia nigra, respectively. PD treatment with stem cells has long been studied by researchers; however, no adequate treatment strategy has been established. The results of studies so far have suggested that stem cell transplantation can be an effective treatment for PD. However, PD is a progressively deteriorating neurodegenerative disease that requires long-term treatment, and this has been insufficiently studied. Thus, we aimed to investigate the therapeutic potential of human adipose-derived stem cells (hASC) for repeated vein transplantation over long-term in an animal model of PD. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice, hASCs were administered on the tail vein six times at two-week intervals. After the last injection of hASCs, motor function significantly improved. The number of dopaminergic neurons present in the nigrostriatal pathway was recovered using hASC transplantation. Moreover, the administration of hASC restored altered dopamine transporter expression and increased neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF), in the striatum. Overall, this study suggests that repeated intravenous transplantation of hASC may exert therapeutic effects on PD by restoring BDNF and GDNF expressions, protecting dopaminergic neurons, and maintaining the nigrostriatal pathway.

Levodopa Therapy for Parkinson's Disease: History, Current Status and Perspectives

2020 ◽  
Vol 19 (8) ◽  
pp. 572-583
Author(s):  
Helle Bogetofte ◽  
Arezo Alamyar ◽  
Morten Blaabjerg ◽  
Morten Meyer
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Substantia Nigra Pars Compacta ◽  
Current Status ◽  
Current Evidence ◽  
Muscle Rigidity

Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by a preferential degeneration of dopaminergic neurons in the substantia nigra pars compacta. This results in a profound decrease of striatal dopamine (DA) levels, which in turn leads to the cardinal motor symptoms of PD; muscle rigidity, hypo- and bradykinesia and resting tremor. Even 50 years after its initial use, the DA precursor levodopa (L-dopa), is still the most effective medical therapy for the symptomatic treatment of PD. Long-term L-dopa treatment is however, unfortunately associated with undesirable side effects such as motor fluctuations and dyskinesias. Furthermore, despite the disease alleviating effects of L-dopa, it is still discussed whether L-dopa has a neurotoxic or neuroprotective effect on dopaminergic neurons. Here we review the history of L-dopa, including its discovery, development and current use in the treatment of PD. We furthermore review current evidence of the L-dopa-induced side effects and perspectives of L-dopa treatment in PD compared to other established treatments such as DA-agonists and the inhibitors of catechol-o-methyltransferase and monoamine oxidase B.

Neurotransmission systems in Parkinson’s disease

2017 ◽  
Vol 28 (5) ◽  
pp. 509-536 ◽  
Author(s):  
Hossein Sanjari Moghaddam ◽  
Ameneh Zare-Shahabadi ◽  
Farzaneh Rahmani ◽  
Nima Rezaei
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
English Literature ◽  
Lewy Bodies ◽  
Motor Symptoms ◽  
Nigrostriatal Pathway ◽  
Sleep Behavior ◽  
Dopaminergic Systems ◽  
Autonomic Disturbances

AbstractParkinson’s disease (PD) is histologically characterized by the accumulation of α-synuclein particles, known as Lewy bodies. The second most common neurodegenerative disorder, PD is widely known because of the typical motor manifestations of active tremor, rigidity, and postural instability, while several prodromal non-motor symptoms including REM sleep behavior disorders, depression, autonomic disturbances, and cognitive decline are being more extensively recognized. Motor symptoms most commonly arise from synucleinopathy of nigrostriatal pathway. Glutamatergic, γ-aminobutyric acid (GABA)ergic, cholinergic, serotoninergic, and endocannabinoid neurotransmission systems are not spared from the global cerebral neurodegenerative assault. Wide intrabasal and extrabasal of the basal ganglia provide enough justification to evaluate network circuits disturbance of these neurotransmission systems in PD. In this comprehensive review, English literature in PubMed, Science direct, EMBASE, and Web of Science databases were perused. Characteristics of dopaminergic and non-dopaminergic systems, disturbance of these neurotransmitter systems in the pathophysiology of PD, and their treatment applications are discussed.

Transplantation of Human Fetal Tissue from Spontaneous Abortions to a Rodent Model of Parkinson's Disease

1996 ◽  
Vol 5 (1) ◽  
pp. 69-75 ◽  
Author(s):  
Takeshi Kondoh ◽  
Lisa L. Pundt ◽  
Jeffrey P. Blount ◽  
John A. Conrad ◽  
Walter C. Low
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Transplantation ◽  
Functional Expression ◽  
Fetal Tissue ◽  
Growth Potential ◽  
Functional Improvement ◽  
Spontaneous Abortions ◽  
Nigrostriatal Pathway ◽  
Human Fetal Tissue

The use of human fetal tissue from elective abortions for cell transplantation therapies has been the subject of considerable controversy. Because of concerns regarding the use of tissue from elective abortions, tissue from spontaneous abortions has been suggested as an alternate donor source. In the present study we have evaluated human fetal tissue from spontaneous abortions to assess its viability, growth potential, and functional expression. Viable cells (Grade I) from a donor (7 wk postconception) were transplanted as a suspension into the striatum of rats with unilateral 6-OHDA lesions of the nigrostriatal pathway. A second group of animals received solid grafts of tissue from a Grade I donor 14 wk postconception. Tissue from Grade II and III specimens were not sufficiently viable for transplantation. Locomotor responses were monitored over a period of 15 wk and revealed an amelioration of rotational asymmetry by animals that received tissue from the 7 wk donor. Animals receiving tissue from the 14 wk donor showed no functional improvement. We found numerous graft-derived tyrosine hydroxylase (TH) immunopositive neurons contained within the transplantation site, and a rich plexus of TH-immunopositive fibers extending into the striatum of animals receiving tissue from the 7 wk donor. Animals receiving tissue from the 14 wk donor exhibited tissue necrosis at the transplant site and were devoid of TH-immunopositive neurons. These results suggest that human fetal ventral mesencephalic cells from spontaneous abortions can survive and develop after transplantation, and rectify locomotor deficits associated with experimental parkinsonism if the donor tissue is of the appropriate gestational age at the time of implantation. Our study further suggests, however, that the availability of tissue from spontaneous abortions of sufficient viability is quite limited and may thus restrict its potential use in cell transplantation therapies for Parkinson's disease.

Long-term Changes in the Nigrostriatal Pathway in the MPTP Mouse Model of Parkinson’s Disease

Neuroscience ◽  
2018 ◽  
Vol 369 ◽  
pp. 303-313 ◽  
Author(s):  
Dongping Huang ◽  
Zishan Wang ◽  
Jiabin Tong ◽  
Mo Wang ◽  
Jinghui Wang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Nigrostriatal Pathway ◽  
Long Term Changes

scholarly journals Focused ultrasound enhanced intranasal delivery of brain derived neurotrophic factor produces neurorestorative effects in a Parkinson’s disease mouse model

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Robin Ji ◽  
Morgan Smith ◽  
Yusuke Niimi ◽  
Maria E. Karakatsani ◽  
Maria F. Murillo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Neurotrophic Factor ◽  
Focused Ultrasound ◽  
Neurodegenerative Disorder ◽  
Control Function ◽  
Early Stage ◽  
Brain Derived Neurotrophic Factor ◽  
Nigrostriatal Pathway

AbstractFocused ultrasound-enhanced intranasal (IN + FUS) delivery is a noninvasive approach that utilizes the olfactory pathway to administer pharmacological agents directly to the brain, allowing for a more homogenous distribution in targeted locations compared to IN delivery alone. However, whether such a strategy has therapeutic values, especially in neurodegenerative disorders such as Parkinson’s disease (PD), remains to be established. Herein, we evaluated whether the expression of tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine catalysis, could be enhanced by IN + FUS delivery of brain-derived neurotrophic factor (BDNF) in a toxin-based PD mouse model. Mice were put on the subacute dosing regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), producing bilateral degeneration of the nigrostriatal pathway consistent with early-stage PD. MPTP mice then received BDNF intranasally followed by multiple unilateral FUS-induced blood-brain barrier (BBB) openings in the left basal ganglia for three consecutive weeks. Subsequently, mice were survived for two months and were evaluated morphologically and behaviorally to determine the integrity of their nigrostriatal dopaminergic pathways. Mice receiving IN + FUS had significantly increased TH immunoreactivity in the treated hemisphere compared to the untreated hemisphere while mice receiving only FUS-induced BBB opening or no treatment at all did not show any differences. Additionally, behavioral changes were only observed in the IN + FUS treated mice, indicating improved motor control function in the treated hemisphere. These findings demonstrate the robustness of the method and potential of IN + FUS for the delivery of bioactive factors for treatment of neurodegenerative disorder.

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