Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One approach to replace lost dopaminergic neurons in Parkinson's disease is to transplant fetal mesencephalic tissue into the striatum. In an attempt to expand the developmental window useful for grafting of mesencephalic tissue and increase the fiber outgrowth from grafted dopaminergic neurons, we have pretreated fetal mesencephalic tissue with the dopaminotrophic factor glial cell line-derived neurotrophic factor (GDNF). Mesencephalic tissue pieces from embryonic day 18-19 Fischer 344 rats were preincubated for 20 min with GDNF (1 microg/microl) or vehicle. Two tissue pieces were then transplanted into the striatum of rats that had been unilaterally lesioned by medial forebrain bundle injections of 6-hydroxydopamine. The animals were tested for apomorphine-induced rotations prior to intracranial grafting. Host rats received intrastriatal injections of 10 microg GDNF or control solution at 10 days and 4 weeks postgrafting. The animals were tested in the rotometer twice monthly following transplantation. Despite the fact that these transplants were from a suboptimal donor stage, the rotations were significantly decreased in both transplanted groups. Immunohistochemical evaluation of the host brains revealed that the overall size of transplanted mesencephalic tissue was significantly increased in the GDNF-treated animals, and that the average size of transplanted tyrosine hydroxylase (TH)-positive neurons was also increased. Furthermore, we found that the innervation density of surrounding host striatal tissue was significantly increased in the GDNF-treated group, as compared with controls. Taken together, these results suggest that treatment of intrastriatal ventral mesencephalon grafts with GDNF can optimize the conditions for intracranial grafting and thus improve the chances for functional recovery following the intrastriatal grafting procedure.
 ...
PMID:Glial cell line-derived neurotrophic factor improves survival of ventral mesencephalic grafts to the 6-hydroxydopamine lesioned striatum. 930 12

Neurological rehabilitation involves the systematic presentation of environmental stimuli and challenges that enable the patient to learn strategies for minimizing their disabilities. Rehabilitation therapy of transplant recipients may be an important factor in enhancing the efficacy of the transplanted organ or tissue to promote functional recovery. Laboratory research and clinical trials on neural transplantation, as an experimental treatment for neurological disorders (e.g., Parkinson's disease, Huntington's disease, and cerebral ischemia), have focused primarily on devising effective surgical implantation strategies with little attention devoted to the interaction between environmental factors and restorative neurosurgery. Exercise training as part of neurological rehabilitation may be an important factor for neural transplantation therapy for Parkinson's disease. Rehabilitation providers are particularly well placed to provide the environment and the support to optimize the behavioral functioning of neural transplant patients in learning to use the new grafted tissue.
 ...
PMID:Implications of neurological rehabilitation for advancing intracerebral transplantation. 932 35

Here we review some of our recent experiments where the neurotoxin 6-hydroxydopamine had been used to unilaterally damage nigro-striatal dopamine neurons in the rat. In this lesion model we studied relationships between the degree of neostriatal dopamine loss, the resulting behavioral deficits, possible recovery therefrom, and mechanisms which may be related to such recovery. Special attention is given to animals with more moderate dopamine lesions, since these may be particularly suitable to study functional recovery. Our behavioral studies showed that initially after lesion (day 1), asymmetries of turning and scanning behavior were observed over a wide range of neostriatal DA depletions, whereas after one week these had recovered to symmetry except in animals with residual neostriatal dopamine levels of 20% or less. Subsequent experiments showed that behavioral asymmetries can also be induced in animals with less severe lesions (residual DA levels 45-65%), since ipsiversive asymmetries in scanning and turning were observed when such animals were challenged systemically with the mixed dopamine receptor agonist apomorphine. Finally, a weak ipsiversive asymmetry could also be induced in such animals by the more selective D2-agonist LY171555, whereas the D1-agonist SKF38393 was ineffective. These results are discussed with respect to the neural mechanisms determining deficits and recovery after such dopamine lesions and their relevance to similar clinical phenomena, namely Parkinson's disease. Here, special attention is given to the role of mechanisms, which can regulate compensatory increases of dopamine activity in those neurons which have survived the lesion.
 ...
PMID:Behavioral and neurochemical dynamics of neurotoxic meso-striatal dopamine lesions. 933 17

Intrastriatal 6-hydroxydopamine injections in rats induce partial lesions of the nigrostriatal dopamine (DA) system which are accompanied by a delayed and protracted degeneration of DA neurons within the substantia nigra. By careful selection of the dose and placement of the toxin it is possible to obtain reproducible and regionally defined partial lesions which are well correlated with stable functional deficits, not only in drug-induced behaviors but also in spontaneous motoric and sensorimotoric function, which are analogous to the symptoms seen in patients during early stages of Parkinson's disease. The intrastriatal partial lesion model has proved to be particularly useful for studies on the mechanisms of action of neurotrophic factors since it offers opportunities to investigate both protection of degenerating DA neurons during the acute phases after the lesion and stimulation of regeneration and functional recovery during the chronic phase of the postlesion period when a subset of the spared nigral DA neurons persist in an atrophic and dysfunctional state. In the in vivo experiments performed in this model glial cell line-derived neurotrophic factor (GDNF) has been shown to exert neurotrophic effects both at the level of the cell bodies in the substantia nigra and at the level of the axon terminals in the striatum. Intrastriatal administration of GDNF appears to be a particularly effective site for induction of axonal sprouting and regeneration accompanied by recovery of spontaneous sensorimotor behaviors in the chronically lesioned nigrostriatal dopamine system.
 ...
PMID:Studies on neuroprotective and regenerative effects of GDNF in a partial lesion model of Parkinson's disease. 936 Dec 95

Recently, we demonstrated amelioration of behavioral deficits associated with 6-hydroxydopamine-induced hemiparkinsonism by transplanting rat testis-derived Sertoli cells into adult male rat brains. In the present study, we used adult female hemiparkinsonian rats to investigate whether the beneficial effects of transplantation of Sertoli cells may be differentially affected by gender of the animal transplant recipient. At 1 month posttransplantation, animals transplanted with Sertoli cells showed functional recovery as revealed by significant reductions in apomorphine-induced rotational behavior and asymmetrical elevated body swing behavior. Control animals that received medium alone did not display any visible behavioral recovery. These results suggest that transplantation of Sertoli cells is not male hormone-dependent and further support the use of these cells as a graft source for Parkinson's disease and other neurological disorders.
 ...
PMID:Intracerebral transplantation of testis-derived sertoli cells promotes functional recovery in female rats with 6-hydroxydopamine-induced hemiparkinsonism. 939 81

Positron emission tomography (PET) and carbon-11-labeled 2B-carbomethoxy-3B-(4-fluorophenyl)tropane (11C-CFT or 11-WIN 35,428) were used as molecular markers for striatal presynaptic dopamine (DA) transporters in a unilateral Parkinson's disease rat neurotransplantation model. In the lesioned striatum, the binding ratio measured by the DA presynaptic marker was reduced to 15% to 35% of the intact side (or unoperated control). After grafting with non-DA cells (from dorsal mesencephalon), the DA binding ratio remained reduced to levels observed before transplantation and rats showed no behavioral recovery. In contrast, after DA neuronal transplantation, behavioral recovery occurred only after the 11C-CFT binding ratio had increased to 75% to 85% of the intact side. This study provides direct in vivo evidence for the dopaminergic molecular basis of functional recovery in the lesioned nigrostriatal system after neural transplantation.
 ...
PMID:In vivo PET imaging in rat of dopamine terminals reveals functional neural transplants. 950 57

We implanted human embryonic mesencephalic tissue into the striatum of 13 patients with idiopathic Parkinson's disease (PD) and three patients with MPTP-induced parkinsonism. Based on our findings so far, as well as data from other groups, the following conclusions can be drawn: First, grafted dopamine (DA) neurons can survive in the human parkinsonian brain and reinnervate part of the host striatum. Second, long-term graft survival, at least up to 6 years after transplantation, is possible in PD despite a progressive degeneration of the patient's own DA neurons. Third, a majority of patients with surviving grafts show long-term improvement of therapeutic value but the symptomatic relief is, in most cases, incomplete. Presently, the most important research strategy to improve the functional recovery after transplantation is to increase the survival of grafted DA neurons and the density and extent of the dopaminergic reinnervation in the striatum.
 ...
PMID:Update on fetal transplantation: the Swedish experience. 961 23

Possible biologic treatments for Parkinson's disease, a disorder caused by the deterioration of dopaminergic neurons bridging the nigrostriatal system, have recently focused on fetal cell transplantation. Because of ethical and tissue availability issues concerning fetal cell transplantation, alternative cell sources are being developed. The adrenal medulla has been used as a cell transplant source because of the capacity of the cells to provide catecholamines and to transform into a neuronal phenotype. However, adrenal tissue transplants have shown limited success, primarily because of their lack of long-term viability. Recently, seeding adrenal chromaffin cells on microcarrier beads has been shown to enhance the cell viability following neural transplantation. In the present study, we further investigated whether transplantation of rat adrenal chromaffin cells seeded on microcarrier beads into the striatum of 6-hydroxydopamine-induced hemiparkinsonian rats would result in a sustained functional recovery. Behavioral tests using the apomorphine-induced rotational and elevated body swing tests up to 12 months posttransplantation revealed a significant behavioral recovery in animals that received adrenal chromaffin cells seeded on microcarrier beads compared to animals that received adrenal chromaffin cells alone, medium alone, or beads alone. Histological examination of tissue at 14 months posttransplantation revealed evidence of tyrosine hydroxylase-positive cells and an on-going glial response in animals transplanted with adrenal chromaffin cells seeded on microcarrier beads, in contrast to absence of such immunoreactive responses in the other groups. These findings support a facilitator role for microcarrier beads in transplantation of adrenal chromaffin cells or other cells that are easily rejected by the CNS.
 ...
PMID:Intrastriatal transplantation of rat adrenal chromaffin cells seeded on microcarrier beads promote long-term functional recovery in hemiparkinsonian rats. 962 55

The aim of Programme 38 of the Swiss National Research Foundation is to enhance collaboration between basic science and clinical application, as related to diseases of the nervous system, over a 5-year period. The 15 ongoing projects are described. They are mainly concerned with mechanisms of pathogenesis and recovery of function, and ways of modifying them therapeutically after traumatic lesions or various diseases of the nervous system such as stroke, Parkinson's disease, Alzheimer's dementia, depression, meningitis, HMSN etc.
 ...
PMID:[National Research Program NFP 38: "Diseases of the nervous system"]. 964 54

Transplantation of embryonic dopamine neurons has evolved as an alternative neurosurgical treatment strategy for patients with Parkinson's disease and it is therefore of great interest to further optimise this procedure in experimental studies. We have applied a modified microtransplantation approach in unilaterally 6-hydroxydopamine lesioned rats and observed a substantial and long-lasting functional recovery in complex spontaneous behaviors, such as skilled forelimb use and stepping behavior. The results demonstrate that the rat model of Parkinson's disease is a highly useful tool to study mechanisms of neural plasticity and regeneration. The ability of dopaminergic grafts to restore complex sensorimotor behaviors in animals also indicate their great potential for the development of a successful clinical application.
 ...
PMID:Dopaminergic graft-induced long-term recovery of complex sensorimotor behaviors in a rat model of Parkinson's disease. 967 98


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>