Topographical Distribution of Morphological Changes in a Partial Model of Parkinson’s Disease—Effects of Nanoencapsulated Neurotrophic Factors Administration

2015 ◽  
Vol 52 (2) ◽  
pp. 846-858 ◽  
Author(s):  
C. Requejo ◽  
J. A. Ruiz-Ortega ◽  
H. Bengoetxea ◽  
A. Garcia-Blanco ◽  
E. Herrán ◽  
...  
2016 ◽  
Vol 363 ◽  
pp. 5-15 ◽  
Author(s):  
Paula Grazielle Chaves da Silva ◽  
Daniel Desidério Domingues ◽  
Litia Alves de Carvalho ◽  
Silvana Allodi ◽  
Clynton Lourenço Correa

2017 ◽  
Vol 1 (2) ◽  
Author(s):  
Gerard W. O'Keeffe ◽  
Shane V. Hegarty ◽  
Aideen M. Sullivan

Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized by the degeneration of midbrain dopaminergic (mDA) neurons and their axons, and aggregation of α-synuclein, which leads to motor and late-stage cognitive impairments. As the motor symptoms of PD are caused by the degeneration of a specific population of mDA neurons, PD lends itself to neurotrophic factor therapy. The goal of this therapy is to apply a neurotrophic factor that can slow down, halt or even reverse the progressive degeneration of mDA neurons. While the best known neurotrophic factors are members of the glial cell line-derived neurotrophic factor (GDNF) family, their lack of clinical efficacy to date means that it is important to continue to study other neurotrophic factors. Bone morphogenetic proteins (BMPs) are naturally secreted proteins that play critical roles during nervous system development and in the adult brain. In this review, we provide an overview of the BMP ligands, BMP receptors (BMPRs) and their intracellular signalling effectors, the Smad proteins. We review the available evidence that BMP–Smad signalling pathways play an endogenous role in mDA neuronal survival in vivo, before outlining how exogenous application of BMPs exerts potent effects on mDA neuron survival and axon growth in vitro and in vivo. We discuss the molecular mechanisms that mediate these effects, before highlighting the potential of targeting the downstream effectors of BMP–Smad signalling as a novel neuroprotective approach to slow or stop the degeneration of mDA neurons in PD.


2017 ◽  
Vol 126 (4) ◽  
pp. 1140-1147 ◽  
Author(s):  
Craig G. van Horne ◽  
Jorge E. Quintero ◽  
Julie A. Gurwell ◽  
Renee P. Wagner ◽  
John T. Slevin ◽  
...  

OBJECTIVE One avenue of intense efforts to treat Parkinson's disease (PD) involves the delivery of neurotrophic factors to restore dopaminergic cell function. A source of neurotrophic factors that could be used is the Schwann cell from the peripheral nervous system. The authors have begun an open-label safety study to examine the safety and feasibility of implanting an autologous peripheral nerve graft into the substantia nigra of PD patients undergoing deep brain stimulation (DBS) surgery. METHODS Multistage DBS surgery targeting the subthalamic nucleus was performed using standard procedures in 8 study participants. After the DBS leads were implanted, a section of sural nerve containing Schwann cells was excised and unilaterally delivered into the area of the substantia nigra. Adverse events were continuously monitored. RESULTS Eight of 8 participants were implanted with DBS systems and grafts. Adverse event profiles were comparable to those of standard DBS surgery. Postoperative MR images did not reveal edema, hemorrhage, or significant signal changes in the graft target region. Three participants reported a patch of numbness on the outside of the foot below the sural nerve harvest site. CONCLUSIONS Based on the safety outcome of the procedure, targeted peripheral nerve graft delivery to the substantia nigra at the time of DBS surgery is feasible and may provide a means to deliver neurorestorative therapy. Clinical trial registration no.: NCT01833364 (clinicaltrials.gov)


2020 ◽  
Author(s):  
Mahmut Atum ◽  
Bekir Enes Demiryurek

Abstract Background: The study aims to investigate the relationship between the progression of idiopathic Parkinson's disease (IPD) and retinal morphology. Methods: The study was carried out with 23 patients diagnosed with early-stage IPD (phases 1 and 2 of the Hoehn and Yahr scale) and 30 age-matched healthy controls. All patients were followed up at least two years, with 6-month intervals (initial, 6th month, 12th month, 18th month, and 24th month), and detailed neurological and ophthalmic examinations were performed at each follow-up. Unified Parkinson's Disease Rating Scale part III (UPDRS Part III) scores, Hoehn and Yahr (H&Y) scores, best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurement, central macular thickness (CMT) and retinal nerve fiber layer (RNFL) thickness were analyzed at each visit. Results: The average age of the IPD and control groups was 43.96 ± 4.88 years, 44.53 ± 0.83 years, respectively. The mean duration of the disease in the IPD group was 7.48 ± 5.10 months at the start of the study (range 0-16). There was no statistically significant difference in BCVA and IOP values between the two groups during the two-year follow-up period (p> 0.05, p> 0.05, respectively). Average and superior quadrant RNFL thicknesses were statistically different between the two groups at 24 months and there was no significant difference between other visits (p = 0.025, p=0.034, p> 0.05, respectively). There was no statistically significant difference in CMT between the two groups during the follow-up period (p> 0.05). Conclusion: Average and superior quadrant RNFL thicknesses were significantly thinning with the progression of IPD.


Author(s):  
Peter Falkai ◽  
Bernhard Bogerts

The traditional domains of neuropathology are well-defined organic brain diseases with an obvious pathology, such as tumours, infections, vascular diseases, trauma, or toxic and hypoxemic changes, as well as degenerative brain diseases (e.g. Alzheimer's disease, Parkinson's disease, and Huntington's chorea). Neuropathological investigations of these brain disorders have been rewarding, because patients with any of these conditions can be expected to have gross morphological or more or less specific neurohistological anomalies related to the clinical symptoms of the disorders. Moreover, the type of brain pathology of these well-defined disease entities is quite homogenous. For example, it is highly unlikely that a patient with Parkinson's disease would not exhibit morphological changes and Lewy bodies in the nigrostriatal system, just as much a person with Huntington's chorea would have a normal striatum, or a patient with Pick'sor Alzheimer's disease would have no changes in the cerebralcortex. In contrast, the history of the neuropathology of psychiatric disorders outside primary degenerative diseases is much more controversial, because no such obvious and homogenous types of brain pathology (as seen in neurological disorders) have yet been detected for the major psychiatric illnesses such as schizophrenia, affective disorders, substance-related disorders, or personality disorders. The scope of this chapter is to summarize the neuropathological findings in schizophrenia, affective disorders, and alcoholism. Tables 2.3.5.1, 2.3.5.2, 2.3.5.3, and 2.3.5.4 highlight the significant findings. It goes beyond the scope of this chapter to review thelarge body of literature on the dementias, including specifically Alzheimer's disease. Concerning this matter, the reader is referred to several comprehensive reviews (e.g. Jellinger and Bancher 1998).


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