Library

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Electronic Resource
    Electronic Resource
    Human fetal dopamine neurons grafted in a rat model of Parkinson's disease: immunological aspects, spontaneous and drug-induced behaviour, and dopamine release (1988)
    Springer
    Experimental brain research 70 (1988), S. 192-208 
    Details
    ISSN: 1432-1106
    Keywords: Neural transplantation ; Spontaneous behaviour ; Human fetus ; Dopamine release ; Intracerebral dialysis ; Immunization Cyclosporin A ; Parkinson's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have used a rat model of Parkinson's disease (PD) to address issues of importance for a future clinical application of dopamine (DA) neuron grafting in patients with PD. Human mesencephalic DA neurons, obtained from 6.5–8 week old fetuses, were found to survive intracerebral cell suspension xenografting to the striatum of rats immunosup-pressed with Cyclosporin A. The grafts produced an extensive new DA-containing terminal network in the previously denervated caudate-putamen, and they normalized amphetamine-induced, apomorphine-induced and spontaneous motor asymmetry in rats with unilateral lesions of the mesostriatal DA pathway. Grafts from an 11.5-week old donor exhibited a lower survival rate and smaller functional effects. As assessed with the intracerebral dialysis technique the grafted DA neurons were found to restore spontaneous DA release in the reinnervated host striatum to normal levels. The neurons responded with large increases in extracellular striatal DA levels after the intrastriatal administration of the DA-releasing agent d-amphetamine and the DA-reuptake blocker nomifensine, although not to the same extent as seen in striata with an intact mesostriatal DA system. DA fiber outgrowth from the grafts was dependent on the localization of the graft tissue. Thus, grafts located within the striatum gave rise to an extensive axonal network throughout the whole host striatum, whereas grafted DA neurons localized in the neocortex had their outgrowing fibers confined within the grafts themselves. In contrast to the good graft survival and behavioural effects obtained in immunosuppressed rats, there was no survival, or behavioural effects, of human DA neurons implanted in rats that did not receive immunosuppression. In addition, we found that all the graft recipients were immunized, having formed antibodies against antigens present on human T-cells. This supports the notion that the human neurons grafted to the non-immunosuppressed rats underwent immunological rejection. Based on an estimation of the survival rate and extent of fiber outgrowth from the grafted human fetal DA neurons, we suggest that DA neurons that can be obtained from one fetus may be sufficient to restore significant DA neurotransmission unilaterally, in one putamen, in an immunosuppressed PD patient.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00271860
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    The properties of cultured fetal human and rat brain tissue and its use as grafts for the relief of the Parkinsonian syndrome (1992)
    Springer
    Neurochemical research 17 (1992), S. 893-900 
    Details
    ISSN: 1573-6903
    Keywords: Human fetal brain cultures ; neural grafting ; dopamine ; Parkinson's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Primary cultures were derived from human fetal ventral mesencephalon and cerebral cortex at 7–11 weeks gestation, and from fetal rat mesencephalon and cortex at embryonic day 14–15. Immunohistochemical analysis of the mesencephalic cultures using antibodies to tyrosine hydroxylase (TH) showed between 0.1–0.5% of human cells to be TH positive and 0.1–1% of rat cells to be TH positive. HPLC analysis of extracts from the cultures showed that they had the ability to synthesise and store dopamine. Implantation of the cultured human and rat mesencephalic tissue into a 6-hydroxydopamine rat model of Parkinson's disease produced marked recovery from amphetamine induced rotational asymmetry in the recipient rats, but no such recovery was observed following implantation of cortical cultures. Histological examination demonstrated the presence of surviving human mesencephalic and cortical grafts at least 6 months after implantation. Implants of cultured fetal rat tissue were less obviously but still significantly effective in these experiments. These rat tissue grafts were detectable for periods of at least 6–8 weeks by histological staining.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00993265
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Human fetal dopamine neurons grafted in a rat model of Parkinson's disease: ultrastructural evidence for synapse formation using tyrosine hydroxylase immunocytochemistry (1988)
    Springer
    Experimental brain research 73 (1988), S. 115-126 
    Details
    ISSN: 1432-1106
    Keywords: Neural transplantation ; Dopamine neurons ; Human fetus ; Tyrosine hydroxylase immunocytochemistry ; Synaptic contacts ; Parkinson's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Human fetal mesencephalic dopamine (DA) neurons, obtained from 6.5–9 week old aborted fetuses, were grafted to the striatum of immunosuppressed rats with 6-hydroxydopamine lesions of the ascending mesostriatal DA pathway. The effects on amphetamine-induced motor asymmetry were studied at various timepoints after grafting. At eight weeks, functional graft effects were not evident but after 11 weeks small effects on motor asymmetry could be monitored and rats tested 19–21 weeks after grafting exhibited full reversal of the lesion-induced rotational behaviour. Four rats were sacrificed at different timepoints between 8 and 20 weeks and the grafted DA neurons were studied in tyrosine hydroxylase (TH) immunocytochemically stained sections at the light and electronmicroscopic level. The grafts contained a total of 500–700 TH-positive neurons in each rat. In one rat sacrificed 8 weeks after grafting the grafted neurons were TH-positive but exhibited virtually no fiber outgrowth. In another rat, sacrificed after 11 weeks, a sparse TH-positive fiber plexus was seen to extend into the adjacent host neostriatum. Two rats sacrificed after 20 weeks both contained TH-positive neurons that gave rise to a rich fiber network throughout the entire host neostriatum, and this fiber network was also seen to extend into the globus pallidus and nucleus accumbens. Very coarse TH-positive processes, identified as dendrites in the electron microscope, projected up to 1.5–2.0 mm from the graft into the host striatum. Ultrastructural analysis revealed that the grafted neurons had formed no TH-positive synaptic contacts with host striatal neurons after 8 weeks, and at 11 weeks some few TH-positive synapses were identified. Twenty weeks after transplantation, abundant TH-positive synaptic contacts with host neurons were seen throughout the neostriatum, and such contacts were identified in the globus pallidus as well. Thus, the present study provides tentative evidence for a time-link between the development of synaptic contacts and the appearance of functional graft effects. Similar to the normal mesostriatal DA pathway, ingrowing TH-positive axons formed symmetric synapses and were mainly seen to contact dendritic shafts and spines. However, in comparison to the normal rat striatum there was a higher incidence of TH-immunoreactive boutons forming synapses onto neuronal perikarya. The TH-positive dendrites that extended into the host striatum were seen to receive non-TH-immunoreactive synaptic contacts, presumably arising from the host neurons. These results suggest that human fetal DA neurons are able to develop a reciprocal synaptic connectivity with the host rat when grafted to the adult brain. Grafting of human fetal DA neurons may therefore be expected to provide a means of restoring regulated synaptic DA release in patients with Parkinson's disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00279666
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...