Transplantation of Embryonic Ventral Mesencephalic Tissue in 6-OHDA Induced Parkinsonism Rat Brain for Cell Based Therapy: A Perspective of Methods

Biswarup Ghosh; Angelo Lepore; George Smith

doi:doi:10.11648/j.ijgg.20160406.16

| Peer-Reviewed

Transplantation of Embryonic Ventral Mesencephalic Tissue in 6-OHDA Induced Parkinsonism Rat Brain for Cell Based Therapy: A Perspective of Methods

Biswarup Ghosh, Angelo Lepore, George Smith

Published in International Journal of Genetics and Genomics (Volume 4, Issue 6)

Received: 18 July 2016 Accepted: 29 July 2016 Published: 22 March 2017

Views: Downloads:

Download PDF

Share This Article

Twitter
Linked In
Facebook

Abstract

Parkinson’s disease (PD) is characterized as a disease of the basal ganglia, with a progressive degeneration of dopaminergic neurons located in the substantia nigra (SN) and projecting to the striatum with subsequently loss of the nigrostriatal circuit. The potential for therapeutic use of cell transplantation for cell replacement has received a great deal of interest. Transplantation with embryonic ventral mesencephalon (VM) is a therapeutic approach for sporadic form of PD. We established unilaterally 6-OHDA lesioned rat model of Parkinson’s disease. Motor behavioral impairment was found compared with normal rat. Embryonic VM tissue was isolated from E 14 (embryonic 14 days) rat brain. We characterized the VM tissue and dissociated cultured dopaminergic cells with tyrosine hydroxylase (TH) immune staining before transplantation in lesioned brain. We observed that the axons of dopaminergic neurons from transplanted VM graft circles round at the site of transplantation in normal adult rat brain. In this paper, we discuss the detailed methodologies which are very useful in preclinical research of cell based therapies for Parkinson’s disease.

Published in	International Journal of Genetics and Genomics (Volume 4, Issue 6)
DOI	10.11648/j.ijgg.20160406.16
Page(s)	79-84
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Transplantation, 6-OHDA, Parkinson’s Disease

References

[1]	Mendez I, Sanchez-Pernaute R, Cooper O, Vinuela A, Ferrari D, Bjorklund L. Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson’s disease. Brain. 2005; 128 (Pt 7): 1498-1510.
[2]	Kordower JH, Freeman TB, Snow BJ, Vingerhoets FJ, E. J. Mufson, Sanberg PR et al. Neuropathological evidence of graft survival and striatal reinnervation after the transplantation of fetal mesencephalic tissue in a patient with Parkinson’s disease. The New England journal of medicine. 1995; 332 (17): 1118-24.
[3]	Kordower JH., Freeman TB, Chen EY, Mufson EJ, Sanberg PR, Hauser RA et al. Fetal nigral grafts survive and mediate clinical benefit in a patient with Parkinson’s disease. Movment Disorders. 1998; 13 (3): 383-93.
[4]	Piccini P, Lindvall O, Björklund A, Brundin P, Hagell P, Ceravolo R et al. Delayed recovery of movement-related cortical function in Parkinson’s disease after striatal dopaminergic grafts. Annals of Neurology. 2000; 48 (5): 689-95.
[5]	Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R et al. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. The New England journal of medicine. 2001; 344 (10): 710-9.
[6]	Olanow CW1, Goetz CG, Kordower JH, Stoessl AJ, Sossi V, Brin MF et al. A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease. Annals of Neurology. 2003 54 (3): 403-14.
[7]	Cadet JL, Brannock C. Free radicals and the pathobiology of brain dopamine systems. Neurochemtry International. 1998; 32 (2): 117-31.
[8]	Blum D, Torch S, Lambeng N, Nissou M, Benabid AL, Sadoul R et al. Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson's disease. Progress in Neurobiology. 2001; 65 (2): 135-72.
[9]	Cohen G. Oxy-radical toxicity in catecholamine neurons. Neurotoxicology. 1984; 5 (1): 77-82.
[10]	Padiglia A, Medda R, Lorrai A, Biggio G, Sanna E, Floris G. Modulation of 6-hydroxydopamine oxidation by various proteins. Biochemical Pharmacology. 1997; 53 (8): 1065-8.
[11]	Palumbo A, Napolitano A, Barone P, d'Ischia M. Nitrite- and peroxide-dependent oxidation pathways of dopamine: 6-nitrodopamine and 6-hydroxydopamine formation as potential contributory mechanisms of oxidative stress- and nitric oxide-induced neurotoxicity in neuronal degeneration. Chemical Research in Toxicology. 1999; 12 (12): 1213-22.
[12]	Schallert T, Fleming SM, Leasure JL, Tillerson JL, Bland ST. CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury. Neuropharmacology. 2000; 39 (5): 777-87.
[13]	Jin Y, Zhang C, Ziemba KS, Goldstein GA, Sullivan PG, Smith GM. Directing dopaminergic fiber growth along a preformed molecular pathway from embryonic ventral mesencephalon transplants in the rat brain. Journal of Neuroscience Research. 2011; 89 (5): 619-27
[14]	Emsley JG, Mitchell BD, Magavi SSP, Arlotta P, Macklis JD. The repair of complex neuronal circuitry by transplanted and endogenous precursors. NeuroRx. 2004; 1 (4): 452-71.
[15]	Bjorklund A, Dunnett SB, Brundin P, Stoessl AJ, Freed CR, Breeze RE et al. Neural transplantation for the treatment of Parkinson's disease. The Lancet Neurology. 2003; 2 (7): 437-45.
[16]	Olson L, Seiger A, Stromberg I (1983) Intraocular transplantation in rodents: a detailed account of the procedure and examples of its use in neurobiology with special reference to brain tissue grafting. Advance Cell Neurobiology. 4: 407-42.
[17]	Dunnett SB, Bjorklund A, Lindvall O. Cell therapy in Parkinson's disease -stop or go? Nature Reviews: Neuroscience. 2001; 2 (5): 365-9.
[18]	Bjorklund A, Schmidt RH, Stenevi U. Functional reinnervation of the neostriatum in the adult rat by use of intraparenchymal grafting of dissociated cell suspensions from the substantia nigra. Cell and Tissue Research. 1980; 212 (1): 39-45.
[19]	Barker RA. Repairing the brain in Parkinson's disease: Where next?Movement Disorders. 2002; 17 (2):233-41.
[20]	Redmond DE, Jr. Cellular replacement therapy for Parkinson's disease -Where are we today? Neuroscientist. 2002; 8 (5):457-88.
[21]	Rosenblad C, Martinez-Serrano A, Bjorklund A. Glial cell line-derived neurotrophic factor increases survival, growth and function of intrastriatal fetal nigral dopaminergic grafts. Neuroscience. 1996; 75 (4):979-85.
[22]	Ostenfeld T, Tai YT, Martin P, Deglon N, Aebischer P, Svendsen CN. Neurospheres modified to produce glial cell line-derived neurotrophic factor increase the survival of transplanted dopamine neurons. Journal of Neuroscience Research. 2002; 69 (6): 955-65.
[23]	Casper D, Engstrom SJ, Mirchandani GR, Pidel A, Palencia D, Cho PH et al. Enhanced vascularization and survival of neural transplants with ex vivo angiogenic gene transfer. Cell Transplantation. 2002; 11 (4):331-49.
[24]	Nikkhah G, Cunningham MG, Jodicke A, Knappe U, Bjorklund A. Improved graft survival and striatal reinnervation by microtransplantation of fetal nigral cell suspensions in the rat Parkinson model. Brain Research. 1994; 633 (1-2): 133-43.
[25]	Winkler C1, Kirik D, Björklund A, Dunnett SB. Transplantation in the rat model of Parkinson's disease: ectopic versus homotopic graft placement. Progress in Brain Research. 2000; 127: 233-265.
[26]	Nikkhah G, Bentlage C, Cunningham MG, Bjorklund A. Intranigral fetal dopamine grafts induce behavioral compensation in the rat Parkinson model. The Journal of Neuroscience. 1994; 14 (6): 3449-61.
[27]	Olsson M, Nikkhah G, Bentlage C, Bjorklund A. Forelimb akinesia in the rat Parkinson model: differential effects of dopamine agonists and nigral transplants as assessed by a new stepping test. The Journal of Neuroscience. 1995; 15 (5 Pt 2): 3863-75.
[28]	Yurek DM. Intranigral Transplants of Fetal Ventral Mesencephalic Tissue Attenuate D1-Agonist-Induced Rotational Behavior. Experimental Neurology. 1997; 143 (1): 1-9
[29]	Collier TJ, Sortwell CE, Elsworth JD, Taylor JR, Roth RH, Sladek JR et al. Embryonic ventral mesencephalic grafts to the substantia nigra of MPTP- treated monkeys: feasibility relevant to multiple-target grafting as a therapy for Parkinson's disease. The Journal of Comparative Neurology. 2002; 442 (4): 320-30.
[30]	Mendez I, Dagher A, Hong M, Gaudet P, Weerasinghe S, McAlister V et al. Simultaneous intrastriatal and intranigral fetal dopaminergic grafts in patients with Parkinson disease: a pilot study. Report of three cases. Journal of Neurosurgery. 2002; 96 (3): 589-96.
[31]	Mukhida K, Baker KA, Sadi D, Mendez I. Enhancement of sensorimotor behavioral recovery in hemiparkinsonian rats with intrastriatal, intranigral, and intrasubthalamic nucleus dopaminergic transplants. The Journal of Neuroscience. 2001; 21 (10): 3521-30.
[32]	Mendez I, Sadi D, Hong M. Reconstruction of the nigrostriatal pathway by simultaneous intrastriatal and intranigral dopaminergic transplants. The Journal of Neuroscience. 1996; 16 (22): 216-27.
[33]	Schwab ME, Kapfhammer JP, Bandtlow CE. Inhibitors of neurite growth. Annual Review of Neuroscience. 1993; 16: 65-95.
[34]	Nikkhah G, Cunningham MG, Cenci MA, McKay RD, Bjorklund A. Dopaminergic microtransplants into the substantia nigra of neonatal rats with bilateral 6-OHDA lesions. I. Evidence for anatomical reconstruction of the nigrostriatal pathway. The Journal of Neuroscience. 1995; 15 (5 Pt 1): 548-61.
[35]	Wictorin K, Brundin P, Sauer H, Lindvall O, Bjorklund A. Long distance directed axonal growth from human dopaminergic mesencephalic neuroblasts implanted along the nigrostriatal pathway in 6-hydroxydopamine lesioned adult rats. The Journal of Comparative Neurology. 1992; 323 (4): 75-94.
[36]	Isacson O, Deacon TW, Pakzaban P, Galpern WR, Dinsmore J, Burns LH. Transplanted xenogeneic neural cells in neurodegenerative disease models exhibit remarkable axonal target specificity and distinct growth patterns of glial and axonal fibres. Nature Medicine. 1995; 1 (11): 189-94.
[37]	Armstrong RJ, Hurelbrink CB, Tyers P, Ratcliffe EL, Richards A, Dunnett SB et al. The potential for circuit reconstruction by expanded neural precursor cells explored through porcine xenografts in a rat model of Parkinson's disease. Experimental Neurology. 2002; 175 (1): 8-111.

Cite This Article

Plain Text BibTeX RIS

APA Style

Biswarup Ghosh, Angelo Lepore, George Smith. (2017). Transplantation of Embryonic Ventral Mesencephalic Tissue in 6-OHDA Induced Parkinsonism Rat Brain for Cell Based Therapy: A Perspective of Methods. International Journal of Genetics and Genomics, 4(6), 79-84. https://doi.org/10.11648/j.ijgg.20160406.16

Copy | Download

ACS Style

Biswarup Ghosh; Angelo Lepore; George Smith. Transplantation of Embryonic Ventral Mesencephalic Tissue in 6-OHDA Induced Parkinsonism Rat Brain for Cell Based Therapy: A Perspective of Methods. Int. J. Genet. Genomics 2017, 4(6), 79-84. doi: 10.11648/j.ijgg.20160406.16

Copy | Download

AMA Style

Biswarup Ghosh, Angelo Lepore, George Smith. Transplantation of Embryonic Ventral Mesencephalic Tissue in 6-OHDA Induced Parkinsonism Rat Brain for Cell Based Therapy: A Perspective of Methods. Int J Genet Genomics. 2017;4(6):79-84. doi: 10.11648/j.ijgg.20160406.16

Copy | Download

@article{10.11648/j.ijgg.20160406.16,
  author = {Biswarup Ghosh and Angelo Lepore and George Smith},
  title = {Transplantation of Embryonic Ventral Mesencephalic Tissue in 6-OHDA Induced Parkinsonism Rat Brain for Cell Based Therapy: A Perspective of Methods},
  journal = {International Journal of Genetics and Genomics},
  volume = {4},
  number = {6},
  pages = {79-84},
  doi = {10.11648/j.ijgg.20160406.16},
  url = {https://doi.org/10.11648/j.ijgg.20160406.16},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijgg.20160406.16},
  abstract = {Parkinson’s disease (PD) is characterized as a disease of the basal ganglia, with a progressive degeneration of dopaminergic neurons located in the substantia nigra (SN) and projecting to the striatum with subsequently loss of the nigrostriatal circuit. The potential for therapeutic use of cell transplantation for cell replacement has received a great deal of interest. Transplantation with embryonic ventral mesencephalon (VM) is a therapeutic approach for sporadic form of PD. We established unilaterally 6-OHDA lesioned rat model of Parkinson’s disease. Motor behavioral impairment was found compared with normal rat. Embryonic VM tissue was isolated from E 14 (embryonic 14 days) rat brain. We characterized the VM tissue and dissociated cultured dopaminergic cells with tyrosine hydroxylase (TH) immune staining before transplantation in lesioned brain. We observed that the axons of dopaminergic neurons from transplanted VM graft circles round at the site of transplantation in normal adult rat brain. In this paper, we discuss the detailed methodologies which are very useful in preclinical research of cell based therapies for Parkinson’s disease.},
 year = {2017}
}

Copy | Download

TY  - JOUR
T1  - Transplantation of Embryonic Ventral Mesencephalic Tissue in 6-OHDA Induced Parkinsonism Rat Brain for Cell Based Therapy: A Perspective of Methods
AU  - Biswarup Ghosh
AU  - Angelo Lepore
AU  - George Smith
Y1  - 2017/03/22
PY  - 2017
N1  - https://doi.org/10.11648/j.ijgg.20160406.16
DO  - 10.11648/j.ijgg.20160406.16
T2  - International Journal of Genetics and Genomics
JF  - International Journal of Genetics and Genomics
JO  - International Journal of Genetics and Genomics
SP  - 79
EP  - 84
PB  - Science Publishing Group
SN  - 2376-7359
UR  - https://doi.org/10.11648/j.ijgg.20160406.16
AB  - Parkinson’s disease (PD) is characterized as a disease of the basal ganglia, with a progressive degeneration of dopaminergic neurons located in the substantia nigra (SN) and projecting to the striatum with subsequently loss of the nigrostriatal circuit. The potential for therapeutic use of cell transplantation for cell replacement has received a great deal of interest. Transplantation with embryonic ventral mesencephalon (VM) is a therapeutic approach for sporadic form of PD. We established unilaterally 6-OHDA lesioned rat model of Parkinson’s disease. Motor behavioral impairment was found compared with normal rat. Embryonic VM tissue was isolated from E 14 (embryonic 14 days) rat brain. We characterized the VM tissue and dissociated cultured dopaminergic cells with tyrosine hydroxylase (TH) immune staining before transplantation in lesioned brain. We observed that the axons of dopaminergic neurons from transplanted VM graft circles round at the site of transplantation in normal adult rat brain. In this paper, we discuss the detailed methodologies which are very useful in preclinical research of cell based therapies for Parkinson’s disease.
VL  - 4
IS  - 6
ER  -

Copy | Download

Author Information

Biswarup Ghosh

Department of Neuroscience, Vickie & Jack Farber Institute for Neuroscience, Thomas Jefferson University, Philadelphia, USA
Angelo Lepore

Department of Neuroscience, Vickie & Jack Farber Institute for Neuroscience, Thomas Jefferson University, Philadelphia, USA
George Smith

Department of Neuronal Rehabilitation, Shriners Hospitals Pediatric Research Center, Temple University, Philadelphia, USA

Download PDF

Sections

Plain Text BibTeX RIS

APA Style

Biswarup Ghosh, Angelo Lepore, George Smith. (2017). Transplantation of Embryonic Ventral Mesencephalic Tissue in 6-OHDA Induced Parkinsonism Rat Brain for Cell Based Therapy: A Perspective of Methods. International Journal of Genetics and Genomics, 4(6), 79-84. https://doi.org/10.11648/j.ijgg.20160406.16

Copy | Download

ACS Style

Biswarup Ghosh; Angelo Lepore; George Smith. Transplantation of Embryonic Ventral Mesencephalic Tissue in 6-OHDA Induced Parkinsonism Rat Brain for Cell Based Therapy: A Perspective of Methods. Int. J. Genet. Genomics 2017, 4(6), 79-84. doi: 10.11648/j.ijgg.20160406.16

Copy | Download

AMA Style

Biswarup Ghosh, Angelo Lepore, George Smith. Transplantation of Embryonic Ventral Mesencephalic Tissue in 6-OHDA Induced Parkinsonism Rat Brain for Cell Based Therapy: A Perspective of Methods. Int J Genet Genomics. 2017;4(6):79-84. doi: 10.11648/j.ijgg.20160406.16

Copy | Download

@article{10.11648/j.ijgg.20160406.16,
  author = {Biswarup Ghosh and Angelo Lepore and George Smith},
  title = {Transplantation of Embryonic Ventral Mesencephalic Tissue in 6-OHDA Induced Parkinsonism Rat Brain for Cell Based Therapy: A Perspective of Methods},
  journal = {International Journal of Genetics and Genomics},
  volume = {4},
  number = {6},
  pages = {79-84},
  doi = {10.11648/j.ijgg.20160406.16},
  url = {https://doi.org/10.11648/j.ijgg.20160406.16},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijgg.20160406.16},
  abstract = {Parkinson’s disease (PD) is characterized as a disease of the basal ganglia, with a progressive degeneration of dopaminergic neurons located in the substantia nigra (SN) and projecting to the striatum with subsequently loss of the nigrostriatal circuit. The potential for therapeutic use of cell transplantation for cell replacement has received a great deal of interest. Transplantation with embryonic ventral mesencephalon (VM) is a therapeutic approach for sporadic form of PD. We established unilaterally 6-OHDA lesioned rat model of Parkinson’s disease. Motor behavioral impairment was found compared with normal rat. Embryonic VM tissue was isolated from E 14 (embryonic 14 days) rat brain. We characterized the VM tissue and dissociated cultured dopaminergic cells with tyrosine hydroxylase (TH) immune staining before transplantation in lesioned brain. We observed that the axons of dopaminergic neurons from transplanted VM graft circles round at the site of transplantation in normal adult rat brain. In this paper, we discuss the detailed methodologies which are very useful in preclinical research of cell based therapies for Parkinson’s disease.},
 year = {2017}
}

Copy | Download

TY  - JOUR
T1  - Transplantation of Embryonic Ventral Mesencephalic Tissue in 6-OHDA Induced Parkinsonism Rat Brain for Cell Based Therapy: A Perspective of Methods
AU  - Biswarup Ghosh
AU  - Angelo Lepore
AU  - George Smith
Y1  - 2017/03/22
PY  - 2017
N1  - https://doi.org/10.11648/j.ijgg.20160406.16
DO  - 10.11648/j.ijgg.20160406.16
T2  - International Journal of Genetics and Genomics
JF  - International Journal of Genetics and Genomics
JO  - International Journal of Genetics and Genomics
SP  - 79
EP  - 84
PB  - Science Publishing Group
SN  - 2376-7359
UR  - https://doi.org/10.11648/j.ijgg.20160406.16
AB  - Parkinson’s disease (PD) is characterized as a disease of the basal ganglia, with a progressive degeneration of dopaminergic neurons located in the substantia nigra (SN) and projecting to the striatum with subsequently loss of the nigrostriatal circuit. The potential for therapeutic use of cell transplantation for cell replacement has received a great deal of interest. Transplantation with embryonic ventral mesencephalon (VM) is a therapeutic approach for sporadic form of PD. We established unilaterally 6-OHDA lesioned rat model of Parkinson’s disease. Motor behavioral impairment was found compared with normal rat. Embryonic VM tissue was isolated from E 14 (embryonic 14 days) rat brain. We characterized the VM tissue and dissociated cultured dopaminergic cells with tyrosine hydroxylase (TH) immune staining before transplantation in lesioned brain. We observed that the axons of dopaminergic neurons from transplanted VM graft circles round at the site of transplantation in normal adult rat brain. In this paper, we discuss the detailed methodologies which are very useful in preclinical research of cell based therapies for Parkinson’s disease.
VL  - 4
IS  - 6
ER  -

Copy | Download