Differential Dissection of the Rat E16 Ventral Mesencephalon and Survival and Reinnervation of the 6-Ohda-Lesioned Striatum by a Subset of Aldehyde Dehydrogenase-Positive th Neurons

1997 ◽  
Vol 6 (3) ◽  
pp. 239-248 ◽  
Author(s):  
Nadia S.K. Haque ◽  
Celeste J. Leblanc ◽  
Ole Isacson
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Functional Recovery ◽  
Dopaminergic Neurons ◽  
Histological Evaluation ◽  
Ventral Mesencephalon ◽  
Th Cells ◽  
Immunohistochemical Markers ◽  
Normal Projection ◽  
Ventral Mesencephalic ◽  
Projection Pattern

The retinoic acid-generating enzyme, aldehyde dehydrogenase (AHD), is expressed in a subpopulation of dopaminergic neurons found in the substantia nigra. Using AHD and tyrosine hydroxylase (TH) as immunohistochemical markers, we determined whether differential dissection of the embryonic (E16) ventral mesencephalon (VM) into its lateral and medial portions contributed equally to the number of TH cells surviving transplantation, if grafted AHD/TH neurons reinnervate the host striatum according to their normal projection patterns, and examined the functional recovery caused by the implanted cells as assessed by amphetamine-induced rotation in a 6-OHDA-lesioned model of Parkinson's disease. The embryonic tissue was transplanted as solid pieces injected via a 20-gauge lumbar puncture needle into the center of the deafferented striatum. Groups received either one complete ventral mesencephalic piece (VM), two medial pieces of ventral mesencephalic tissue (MVM), or two lateral pieces of ventral mesencephalic tissue (LVM). Both VM and MVM groups showed a significant decrease in amphetamine-induced rotation over time and, there was no difference in the degree of reduction observed between the two groups. Histological evaluation of the transplants revealed a much larger total number of surviving TH cells in grafts from the VM and MVM groups compared to the LVM group. Surviving AHD/TH neurons were found in all groups. Whereas TH staining of the transplanted striatum displayed a halo of graft-derived fibers all around the transplant and integration of these fibers into the host neuropil, AHD staining showed a preferential reinnervation of the dorsolateral striatum corresponding to the normal projection pattern of AHD/TH neurons. In summary, selective dissection of the embryonic ventral mesencephalon is possible, functional recovery as assessed by amphetamineinduced rotation in animals transplanted with MVM is similar to that seen in animals grafted with VM, and AHD/TH neurons have a selective reinnervation pattern in the PD transplantation paradigm. These findings may have implications for the grafting of fetal mesencephalic tissue in PD patients.

scholarly journals Intrastriatal Ventral Mesencephalic Xenografts of Porcine Tissue in Rats: Immune Responses and Functional Effects

2000 ◽  
Vol 9 (2) ◽  
pp. 261-272 ◽  
Author(s):  
Lena C. Larsson ◽  
Kimberly A. Czech ◽  
Patrik Brundin ◽  
Håkan Widner
Keyword(s):  
Immune Responses ◽  
Graft Survival ◽  
Functional Recovery ◽  
Dopaminergic Neurons ◽  
Immunosuppressive Treatment ◽  
Neural Tissue ◽  
Scar Tissue ◽  
Rat Striatum ◽  
Intracerebral Transplantation ◽  
Ventral Mesencephalic

Transplantation of neural tissue from other species has the potential to improve function in patients with neurodegenerative disorders. We investigated the functional effects of embryonic porcine dopaminergic neurons transplanted in a rat model of Parkinson's disease and the immune responses to the grafts in immunosuppressed and nonimmunosuppressed hosts. Twenty-three rats with unilateral 6-hydroxydopamine lesions received dissociated, 27-day-old embryonic porcine ventral mesencephalic tissue in the right striatum. Eighteen rats received cyclosporine (10 mg/kg, IP, daily) during the whole period of 14 weeks, in combination with prednisolone (20 mg/kg, IP, daily) the first 4 days. Five rats served as nonimmunosuppressed controls. All rats were tested for amphetamine-induced rotational behavior at 3-week intervals. Two immunosuppressed rats were excluded due to severe side effects of the treatment. Functional recovery was seen in 9 of 16 immunosuppressed rats at 12 weeks. Six animals remained functionally recovered at 14 weeks and contained an average of 5750 ± 1450 (SEM) dopaminergic neurons. Between 9 and 14 weeks, three immunosuppressed rats rejected their grafts, based on rotation scores and immunohistochemical demonstration of cell infiltrates. One additional immunosuppressed rat showed evidence of ongoing rejection at 14 weeks. The striata in animals with ongoing or recent rejection contained large numbers of CD4- and CD8-positive lymphocytes, NK cells, macrophages, and microglia cells, whereas scar tissue was found in rats with grafts rejected at earlier time points (n = 11). Embryonic porcine ventral mesencephalic tissue matures in the adult rat striatum, reinnervates the host brain, and restores behavioral defects. Immunosuppressive treatment was necessary for long-term graft survival and functional recovery, but did not sufficiently protect from rejection mechanisms. Porcine neural tissue is an interesting alternative to embryonic human tissue for intracerebral transplantation in neurodegenerative diseases. However, to achieve stable graft survival in discordant xenogeneic combinations, an appropriate immunosuppressive treatment or donor tissue modifications are needed.

Xenotransplantation of Porcine Fetal Ventral Mesencephalon in a Rat Model of Parkinson's Disease: Functional Recovery and Graft Morphology

1996 ◽  
Vol 140 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Wendy R. Galpern ◽  
Lindsay H. Burns ◽  
Terrence W. Deacon ◽  
Jonathan Dinsmore ◽  
Ole Isacson
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Functional Recovery ◽  
Rat Model ◽  
Ventral Mesencephalon ◽  
Graft Morphology

Intranigral Grafts of Fetal Ventral Mesencephalic Tissue in Adult 6-Hydroxydopamine-Lesioned Rats can Induce Behavioral Recovery

1997 ◽  
Vol 6 (3) ◽  
pp. 267-276 ◽  
Author(s):  
R.E. Johnston ◽  
Jill B. Becker
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cyclosporine A ◽  
Ventral Mesencephalon ◽  
Behavioral Recovery ◽  
Treatment Conditions ◽  
Movement Sequence ◽  
Ventral Mesencephalic ◽  
6 Hydroxydopamine ◽  
Disease Specific

Intrastriatal grafts of fetal ventral mesencephalon in rats with unilateral 6-hydroxydopamine lesions can reduce and even reverse rotational behavior in response to direct and indirect dopamine agonists. These grafts can ameliorate deficits on simple spontaneous behaviors, but do not improve complex behaviors that require the skilled integration of the use of both paws. We report here that rats with grafts into the DA-depleted substantia nigra, that receive cyclosporine A, can experience recovery on spontaneous behaviors that mimic those observed in Parkinson's disease. Specific cyclosporine A treatment conditions can differentially affect whether intranigral grafts normalize paw use during initiation or termination of a movement sequence. These findings may have important implications for the treatment of Parkinson's disease.

Effects of creatine treatment on the survival of dopaminergic neurons in cultured fetal ventral mesencephalic tissue

Neuroscience ◽  
2005 ◽  
Vol 133 (3) ◽  
pp. 701-713 ◽  
Author(s):  
R.H. Andres ◽  
A.W. Huber ◽  
U. Schlattner ◽  
A. Pérez-Bouza ◽  
S.H. Krebs ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Ventral Mesencephalic

The Age of Striatum Determines the Pattern and Extent of Dopaminergic Innervation: a Nigrostriatal Double Graft Study

1997 ◽  
Vol 6 (3) ◽  
pp. 287-296 ◽  
Author(s):  
Ingrid Stromberg ◽  
Lars Björklund ◽  
Petter Forander
Keyword(s):  
Nerve Fiber ◽  
Growth Pattern ◽  
Dopaminergic Neurons ◽  
Nerve Fibers ◽  
Growth Patterns ◽  
Ganglionic Eminence ◽  
Fiber Network ◽  
Lateral Ganglionic Eminence ◽  
Ventral Mesencephalic ◽  
Dopaminergic Grafts

In animal models of Parkinson's disease, transplanted fetal mesencephalic dopaminergic neurons can innervate the dopamine-depleted host brain, but it is unclear why large portions of the host striatum are left uninnervated. During normal development, the dopaminergic innervation first occurs in the form of a dense patchy pattern in the striatum, followed by a widespread nerve fiber network. Using intraocular double grafts we have investigated dopaminergic growth patterns initiated when ventral mesencephalic grafts innervate striatal targets. The fetal lateral ganglionic eminence was implanted into the anterior eye chamber. After maturation in oculo, fetal ventral mesencephalon was implanted and placed in contact with the first graft. In other animals the two pieces of tissue were implanted simultaneously. Tyrosine hydroxylase (TH) immunohistochemistry revealed a pattern of dense TH-positive patches throughout the total volume of the striatal grafts in simultaneously transplanted cografts, while a widespread, less dense, pattern was found when mature striatal transplants were innervated by fetal dopaminergic grafts. To investigate which type or types of growth patterns that developed after grafting to striatum in situ of an adult host, fetal ventral mesencephalic tissue was implanted into the lateral ventricle adjacent to the dopamine-lesioned striatum. After maturation of the mesencephalic graft, the fetal lateral ganglionic eminence was implanted into the reinnervated part of the host striatum. TH immunohistochemistry revealed a few nerve fibers within the striatal graft and the growth pattern was of the widespread type. In conclusion, grafted dopaminergic neurons preferably innervate mature striatum with a widespread sparse nerve fiber network, while the innervation of the immature striatum occurs in the form of dense patches. Furthermore, when the patchy pattern is formed, the total volume of the striatal target is innervated while growth of the widespread type terminates prior to reaching distal striatal parts. Thus, the growth pattern seems essential to the final volume that is innervated. Once the widespread growth pattern is initiated, the presence of immature striatum does not change the dopaminergic growth pattern.

Microcarrier Enhanced Survival of Human and Rat Fetal Ventral Mesencephalon Cells Implanted in the Rat Striatum

1997 ◽  
Vol 6 (6) ◽  
pp. 579-584 ◽  
Author(s):  
Samuel Saporta ◽  
Cesario Borlongan ◽  
Joann Moore ◽  
Elizabeth Mejia-Millan ◽  
Stacey L. Jones ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Chromaffin Cells ◽  
Rat Striatum ◽  
Ventral Mesencephalon ◽  
Poor Survival ◽  
Systemic Immunosuppression ◽  
Ventral Mesencephalic ◽  
Transplant Site ◽  
Mesencephalic Cells

The transplantation of tissue containing dopamine-producing cells into the mammalian central nervous system is an emerging treatment for Parkinson's disease, despite relatively poor survival of implanted tissue. Recent evidence has suggested that Cytodex microcarriers enhance the survival of dopaminergic rat chromaffin cells transplanted into the rat striatum in the absence of immunosuppression. The current study was undertaken to evaluate the survival of rat and human fetal ventral mesencephalic neurons (VM) implanted alone or after attachment to microcarriers in the striatum of rats without immunosuppression. Rat fetal VM neurons demonstrated enhanced survival in the rat striatum when transplanted on microcarriers, compared to their transplantation alone during the 3-mo period examined in the present study. Transplants of human fetal VM neurons on microcarriers also survived remarkably well in the rat striatum without systemic immunosuppression. In contrast, human fetal VM cells transplanted alone into the rat striatum did not survive without systemic immunosuppression. There was no evidence of TH fiber sprouting in the vicinity of any transplant site. These data indicated that Cytodex microcarriers provide enhanced survival of both rat allograft and human xenograft fetal mesencephalic cells in the rat striatum without the necessity of systemic immunosuppression, perhaps by inducing a unique neuron–glia environment.

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