Transplantation of adrenal medullary tissue to striatum in parkinsonism

Backlund, Erik‐Olof; Granberg, Per‐Ola; Hamberger, Bertil; Knutsson, E; Mårtensson, Anders; Sedvall, Göran; Seiger, Åke; Olson, Lar̀s

doi:10.3171/jns.1985.62.2.0169

Cited by 532 publications

(153 citation statements)

References 25 publications

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“…Prior to and conings of the primate caudate and putamen preceding earliest movement-related muscle activity show electrical comitant with these primate studies, a number of clinical trials using adrenal medulla grafts were attempted; howactivity in the caudate and putamen (45), suggesting that both may be critical targets for neural replacement. ever, these resulted in transient behavioral benefits and high morbidity (7,9,38,51,64,67,90). Postmortem studies Not only did these double-blinded trials fail to demonstrate uniform functional benefit, the induction of a confirmed the nonhuman primate experiments; graft survival was poor and the degenerating grafts induced a serious new side effect called graft-induced dyskinesias was noted.…”

Section: Genetic Modelsmentioning

confidence: 99%

Neural Repair Strategies for Parkinson's Disease: Insights from Primate Models

et al. 2006

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Nonhuman primate models of Parkinson's disease (PD) have been invaluable to our understanding of the human disease and in the advancement of novel therapies for its treatment. In this review, we attempt to give a brief overview of the animal models of PD currently used, with a more comprehensive focus on the advantages and disadvantages presented by their use in the nonhuman primate. In particular, discussion addresses the 6-hydroxydopamine (6-OHDA), 1-methyl-1,2,3,6-tetrahydopyridine (MPTP), rotenone, paraquat, and maneb parkinsonian models. Additionally, the role of primate PD models in the development of novel therapies, such as trophic factor delivery, grafting, and deep brain stimulation, are described. Finally, the contribution of primate PD models to our understanding of the etiology and pathology of human PD is discussed.Key words: Parkinson's disease; Nonhuman primates; Animal models; Therapeutics PARKINSON'S DISEASEsymptoms have taken a backseat to the motor problems that most often define PD. Although the etiology of PD Societal Impact and Biological Features remains unclear, degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) has It has been estimated that over 1 million Americans are currently living with Parkinson' disease (PD) with been recognized as a primary pathology (82). Loss of DA neurons in the SN results in increased inhibition of an additional 40,000 persons in the US diagnosed each year, producing an estimated annual cost of greater than excitatory output from the thalamus to the motor cortex, causing a generalized inhibition of both movement initi-$5.6 billion (88). While PD is often considered a disease of the elderly and age is clearly the most powerful risk ation and execution. Histology of nigral tissue from PD patients shows decreased numbers of DA neurons and factor, many patients have an early onset. In this regard, it is significant that approximately 15% of patients are the presence of Lewy bodies, intracellular inclusions, in remaining neurons. Degeneration of SNpc is associated diagnosed before the age of 50 (88).In its classical description, PD is a neurodegenerative with aberrant neuronal plasticity and molecular signaling within the basal ganglia, resulting in a chronic imdisorder affecting primarily movement, muscle control, and balance. Diagnostic hallmarks of PD include cogbalance of insufficient DA levels, aggravated by unregulated cholinergic and glutamatergic signaling (82). wheel rigidity, resting tremor, bradykinesia, masked faces, stooped posture, and shuffling gait (88). NonmoPatients are typically asymptomatic until greater than 60% of the DA cell number is lost from the substantia tor symptoms such as dementia, depression, constipation, pain, and sleep disturbances are serious unmet nigra (88). Therefore, a critical component in effectively treating the nigrostriatal pathology in PD will necessitate needs of PD patients. Scientifically, these nonmotor

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Section: Genetic Modelsmentioning

confidence: 99%

Neural Repair Strategies for Parkinson's Disease: Insights from Primate Models

et al. 2006

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“…By the 1980s, groups in Sweden and Mexico were reporting transplantation of autologous adrenal tissue into the brains of patients with PD via both open craniotomy and stereotactic approaches. 39,40 Although the thalamus had been the preferred target for patients with PD prior to the introduction of L-dopa, 17 Laitinen et al 41,42 popularized pallidotomy as the principal procedure for patients with advanced, medically refractory PD in the early 1990s. There were several reasons for this change: 1) the patients may have had more advanced disease in the 1990s than in the 1950s and 1960s since they had failed L-dopa, 2) DeLong et al's 43 nonhuman primate model pointed to a more important role in the circuitry of PD for the globus pallildus pars interna (GPi) than the ventrointermedialis nucleus (Vim) of the thalamus, and 3) better outcome measures may have detected differences that were initially missed in the 1950s and 1960s.…”

Section: The Resurgence Of Surgical Treatment For Movement Disordersmentioning

confidence: 99%

The History and Future of Deep Brain Stimulation

2008

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Summary:The advancement of electrical stimulation of the central nervous system has been a story of fits and bursts with numerous setbacks. In many ways, this history has paralleled the history of medicine and physics. We have moved from anecdotal observation to double-blinded, prospective randomized trials. We have moved from faradic stimulation to systems that lie completely under the skin and can deliver complex electrical currents to discrete areas of the brain while controlled through a device that is not much bigger than a PDA. This review will discuss how deep brain stimulation has developed into its current form, where we see the field going and the potential pitfalls along the way.

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“…In pioneering work performed by Olson, Seiger and Backlund and their co-workers [3,4], autologous adrenal medulla cells were implanted into striatum of four PD patients to provide a local catecholamine source but the beneficial effects were minimal. Similarly, after an initial hype with open microsurgery and pieces of adrenal medulla tissue placed in the caudate nucleus [5], this method was abandoned because of lack of efficacy and adverse effects.…”

Section: Introductionmentioning

confidence: 99%

Treatment of Parkinson's disease using cell transplantation

Lindvall¹

2015

Phil. Trans. R. Soc. B

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The clinical trials with intrastriatal transplantation of human fetal mesencephalic tissue, rich in dopaminergic neurons, in Parkinson's disease (PD) patients show that cell replacement can work and in some cases induce major, long-lasting improvement. However, owing to poor tissue availability, this approach can only be applied in very few patients, and standardization is difficult, leading to wide variation in functional outcome. Stem cells and reprogrammed cells could potentially be used to produce dopaminergic neurons for transplantation. Importantly, dopaminergic neurons of the correct substantia nigra phenotype can now be generated from human embryonic stem cells in large numbers and standardized preparations, and will soon be ready for application in patients. Also, human induced pluripotent stem cell-derived dopaminergic neurons are being considered for clinical translation. Available data justify moving forward in a responsible way with these dopaminergic neurons, which should be tested, using optimal patient selection, cell preparation and transplantation procedures, in controlled clinical studies.

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Transplantation of adrenal medullary tissue to striatum in parkinsonism

Cited by 532 publications

References 25 publications

Neural Repair Strategies for Parkinson's Disease: Insights from Primate Models

Neural Repair Strategies for Parkinson's Disease: Insights from Primate Models

The History and Future of Deep Brain Stimulation

Treatment of Parkinson's disease using cell transplantation

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