Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0599766 (functional recovery)
 13,441 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Injectable local drug delivery formulations-so-called microspheres have recently been developed, in which drugs are microencapsulated within biocompatible and biodegradable copolymer excipients like poly[DL-lactide-co-glycolide]. In view of its potential therapeutical usefulness, we have studied the microsphere methodology as a means to substitute for experimentally induced subnormal levels of endogenous dopamine (DA). Administration of 6-hydroxydopamine (6-OH-DA) unilaterally in the medial forebrain bundle of rats results in an up-regulation of postsynaptic receptors in the denervated striatum, functionally manifested as contralateral rotational behavior after apomorphine. DA microspheres were implanted in the denervated striatum. The majority of the rats displayed an attenuation of the contralateral rotational behavior induced by apomorphine up to 8 wk postimplantation. Immunocytochemical observations unexpectedly demonstrated growth of DA and tyrosine hydroxylase immunoreactive fibers in the denervated striatum. Interestingly, there was an apparent correlation between functional recovery and the degree of growth of DA fibers. The present results suggest that implantation of DA microspheres may promote DA fiber growth and extended recovery of surviving DA neurons, and, therefore, could be of therapeutic usefulness in Parkinson's disease.
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PMID:Dopamine fiber growth induction by implantation of synthetic dopamine-containing microspheres in rats with experimental hemi-parkinsonism. 135 53

The effects of GM1 ganglioside administration on functional recovery and recovery of caudate nucleus dopamine levels have been assessed in cats made parkinsonian by administration of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Cats made severely parkinsonian by MPTP administration began to show spontaneous functional recovery by the third week after MPTP, as had been observed in previous studies with this model. In contrast, cats with similar initial impairment but which received 3 weeks of GM1 ganglioside treatment (30 mg/kg, i.p. daily) showed an accelerated behavioral recovery, showing significant functional improvement after the first week of GM1 treatment and almost normal function by the end of the third week of treatment. The GM1-treated cats had caudate nucleus dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and HVA levels significantly increased above levels measured in saline-treated MPTP control cats. A second group of cats received MPTP only until the first signs of parkinsonism were observed and thus overall had a less severe initial syndrome than the cats described previously. Again, while all cats showed functional recovery over time, the recovery process was accelerated in GM1-treated cats. GM1 treatment also caused a significant increase in caudate dopamine levels in these cats. These results suggest that GM1 ganglioside administration can result in increased dopamine levels even in the heavily denervated striatum and accelerate functional recovery after an MPTP-induced lesion of the nigrostriatal dopamine system in the cat. This suggests that GM1 or other trophic factor therapies may be fruitful treatment strategies for a disorder of nigrostriatal function such as Parkinson's disease.
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PMID:MPTP-induced parkinsonism: acceleration of biochemical and behavioral recovery by GM1 ganglioside treatment. 161 17

Animal experimentation is necessary to identify the optimal parameters and procedures for clinical application of neural tissue transplantation. Experiments in animal models of Parkinson's disease are briefly reviewed. Embryonic nigral tissues survive transplantation well and yield good functional recovery on a variety of motor tests. The age of the donor, the implantation technique, and the site of placement in the host brain all influence graft efficacy. Nevertheless there are theoretical limits to the power of current procedures, and even under optimal circumstances full recovery cannot be expected.
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PMID:Towards a neural transplantation therapy for Parkinson's disease: experimental principles from animal studies. 179 63

In rats with a lesion of the dopaminergic nigrostriatal pathway induced by 6-hydroxydopamine (6-OHDA), the histologic and functional viability of the striatal implant of fetal mesencephalic substantia nigra has been demonstrated. In the same model, the implant of adrenal medulla is also effective but less lasting. In monkeys with parkinsonism induced by MPTP there are suggestions of effectiveness of the fetal mesencephalic implant and also of other tissues such as placenta and sympathetic ganglion or sural nerve. Now the possibility of a better functional recovery by acting on the neuronal growth factors is being evaluated. In patients with Parkinson's disease, the accumulated experience indicates that 32% are improved with adrenal medulla implant, but the best candidates are those who also benefit from the available drug therapy without the risks of surgery. The implant of fetal tissue has been carried out in about 90 patients, with very variable results. In the most thoroughly investigated patients the improvement has been moderate. The future research points to the identification of the factors that control and regulate striatal reinnervation and the use of genetically determined cells. That would permit a more precise reposition of the biochemical deficiency in Parkinson's disease, without the ethical and practical problems derived from the use of fetal tissue.
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PMID:[Cellular transplants for Parkinson's disease]. 187 45

Intracerebral grafting of dopamine containing adrenal chromaffin cells to the brain of experimental animals can ameliorate the symptoms of experimentally induced Parkinson's disease. Clinical trials of adrenal autograft to the patients with Parkinson's disease are on-going with variable results and autopsy cases show poor survivability of grafted chromaffin cells. The present study was performed to determine if transected peripheral nerve could provide sufficient nerve growth factor to enhance the survivability of grafted chromaffin cells. Survivability of grafted chromaffin cells increased when cografts with sciatic nerve were performed, and host dopaminergic fiber recovery was more prominent in mice with cografts than in mice with adrenal grafts alone. Although this enhanced survivability and recovery of host fibers were seen in cografted mice from aging donors, the degree of these effects was greater in cografted mice from young donors. Considering these results, we suggest that methods to increase the survivability of grafted chromaffin cells be explored more deeply because such survivability might be closely related to the functional recovery of patients with Parkinson's disease, using this grafting procedure.
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PMID:[Cografting technique in the treatment of Parkinson's disease]. 194 75

Schwann cells from transected peripheral nerve segments are known to produce nerve growth factor (NGF). We performed adrenal medullary grafts or cografts of adrenal medulla and sciatic nerve into the striatum of MPTP-treated young adult mice, and compared the survivability of grafted chromaffin cells and the recovery of intrinsic host DA fibers using computerized image analysis of tyrosine hydroxylase (TH)-immunoreactive (IR) fibers and neurochemical analysis with high performance liquid chromatography (HPLC). Adrenal medullary chromaffin cells cografted with sciatic nerve survived better than those in adrenal grafts alone; host DA fiber recovery was more prominent in mice with cografts than in mice with adrenal grafts alone. A large number of TH-IR surviving cells in cografted mice showed long neuronal processes which were rarely seen in the mice receiving adrenal graft alone. We conclude that cograft of adrenal medulla and sciatic nerve promotes intrinsic host DA fiber recovery better than adrenal medulla grafts alone, and that survivability of grafted chromaffin cell may promote host DA fiber recovery. Adrenal medullary autografts have been used in patients with Parkinson's disease; we suggest that if this approach is to be used in the future, methods to increase the survivability of grafted chromaffin cells, such as co-grafting with pieces of peripheral nerve, be considered to enhance the survivability of the chromaffin cells, which might be closely related to the functional recovery of the patients by this grafting procedure. Of course, such strategies as the present cografting approach must be demonstrated to work in older animals using older donor tissue before proceeding to this next step in humans.
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PMID:Cografts of adrenal medulla with peripheral nerve enhance the survivability of transplanted adrenal chromaffin cells and recovery of the host nigrostriatal dopaminergic system in MPTP-treated young adult mice. 198 43

Transplants of embryonic central nervous system tissue have long been used to study axon growth during development and regeneration, and more recently to promote recovery in models of human diseases. Transplants of embryonic substantia nigra correct some of the deficits found in experimental Parkinson's disease, for example, by mechanisms that are thought to include release of neurotransmitter and reinnervation of host targets, as well as by stimulating growth of host axons. Similar mechanisms appear to allow intraspinal transplants of embryonic brainstem to reverse locomotor and autonomic deficits due to experimental spinal cord injuries. Embryonic spinal cord transplants offer an additional strategy for correcting the deficits of spinal cord injury because, by replacing damaged populations of neurons, they may mediate the restoration of connections between host neurons. We have found that spinal cord transplants permit regrowth of adult host axons resulting in reconstitution of synaptic complexes within the transplant that in many respects resemble normal synapses. Transplants of fetal spinal cord may also contribute to behavioral recovery by rescuing axotomized host neurons that otherwise would have died. Electrophysiological and behavioral investigations of functional recovery after intraspinal transplantation are preliminary, and the role of transplants in the treatment of human spinal cord injury is uncertain. Transplants are contributing to our understanding of the mechanisms of recovery, however, and are likely to play a role in the development of rational treatments.
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PMID:Intraspinal transplants. 201 82

C57BL/6 mice show decreased dopaminergic fibers and dopamine concentration in the striatum following systemic injection of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). We have investigated the effect of adrenal medullary grafts into the striatum of young mice treated with MPTP. Enhanced recovery of the host nigrostriatal dopaminergic system was observed in those adrenal medullary grafted mice. However, this recovery was influenced by the survivability of grafted chromaffin cells and adrenal chromaffin cells from younger donors survived better than those from older donors. Since adrenal chromaffin cells contain several kinds of neurotrophic factors such as basic fibroblast growth factor and gangliosides, survivability of those grafted chromaffin cells may play an important role concerning recovery of the host intrinsic dopaminergic fibers. Adrenal medullary grafts to the patients with Parkinson's disease are currently under way in a large number of hospitals and we suggest more consideration be given to methods which lead to enhance the grafted chromaffin cell survival, since those survivability might be closely related to the functional recovery of these patients.
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PMID:[Adrenal medullary graft induces recovery of the host nigrostriatal dopaminergic system in MPTP-induced mouse model of Parkinson's disease]. 208 33

We elicited motor evoked potentials (MEPs) using transcortical magnetic stimulation in 150 control subjects aged 14 to 85 years and 275 patients with a variety of diseases. There were no significant side effects. Cortex-to-target muscle latencies measured 20.2 +/- 1.6 ms (thenar), 14.2 +/- 1.7 ms (extensor digitorum communis), 9.4 +/- 1.7 ms (biceps), and 27.2 +/- 2.9 ms (tibialis anterior). Central motor delay between the cortex and the C-7 and L-5 measured 6.7 +/- 1.2 ms and 13.1 +/- 3.8 ms, respectively. Mean spinal cord motor conduction velocity measured 65.4 m/s. MEP amplitude expressed as a percentage of the maximum M wave was never less than 20% of the M wave. A value of less than 10% is considered abnormal. MEP latency increases linearly with age and central motor delay is longer in older subjects. Compound muscle action potentials and absolute MEP amplitudes decreased linearly with age. In multiple sclerosis (MS), MEP latency and central delay were often very prolonged. The MEP was more sensitive than the SEP in MS. In amyotrophic lateral sclerosis, MEP latencies were only modestly prolonged; the characteristic abnormality was reduced amplitude. When pseudobulbar features predominated MEPs were often absent. The MEP was of normal latency in Parkinson's disease, but age-related amplitude was often increased. MEP latency and amplitude were normal in Huntington's disease. Abnormal MEPs persisted several months after stroke despite good functional recovery. The MEP could be used to advantage to demonstrate proximal conduction slowing and block in demyelinating neuropathies. In plexopathy, ability to elicit an MEP several days after onset of paresis was good evidence of neuronal continuity in motor fibers.
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PMID:AAEM minimonograph #35: Clinical experience with transcranial magnetic stimulation. 793 34

Parkinson's disease (PD) is a progressive neurodegenerative disorder in which the primary pathology is thought to be a loss of dopaminergic neurons in the substantia nigra (SN). The mainstay of treatment has been the use of the drug L-DOPA, a drug that crosses the blood-brain barrier and is converted to dopamine. Recently, intracerebrally implanted grafts of adrenal tissue to promote functional recovery in nigral-damaged recipient animals and patients have been successfully performed. The recovery in these cases is said to be due to the dopamine present in the grafted adrenal tissue. This explanation has several fallacies, however. It is the contention of this paper that substance P is the active agent in the grafted tissue. This raises the possibility of improving the treatment for PD by the use of grafted tissue that is a purer source of SP or SP agonists.
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PMID:Adrenal grafting for Parkinson's disease: a role for substance P. 247 50


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