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)

Division of the axons of adrenergic neurones by crushing the postganglionic nerve trunks of rat superior cervical ganglia (SCG) at 6 days of age resulted in a permanent atrophy of the SCG reflected by a persistent decrease in the total protein content and in the activities of the enzymes tyrosine hydroxylase and DOPA decarboxylase. Administration of nerve growth factor (NGF) to rats with unilateral axotomy at a dose of 10 mug/g/day for the period 7-21 days of age resulted in hypertrophy of both normal and axotomised SCG. There was a progressive rise in the total protein content and in the activities of the two enzymes till the end of the treatment period in both SCG. After treatment ceased there was a progressive fall in the total protein content and activities of the two enzymes reaching a stable level after 4 weeks. The level reached for treated unoperated SCG remained elevated when compared to untreated control SCG. Axotomised treated SCG had approximately the same biochemical parameters as untreated control SCG and very much elevated over untreated axotomised SCG. These final levels persisted for at least 56 days after treatment had ceased. Animals showed a persistent ptosis after axotomy at 6 days of age but treatment with NGF resulted in a functional recovery by 11 weeks of age. It is suggested that there is normally a retrograde transfer of a factor durind development from the target cell to the perikarya of the neurone permitting survival if the appropriate connections are made. Failure to make such a contact results in cedd death. The cell death occurring normally, and the cell death resulting from axotomy, can both be prevented by NGF treatment leading to an hypertrophy of both SCG. This consistent with the hypothesis than NGF is the retrograde trophic agent for the sympathetic nervous system in the developing animal.
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PMID:The response of adrenergic neurones to axotomy and nerve growth factor. 23 22

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

Behavioral improvement has been seen in hemiparkinsonian animals after surgical lesions of the denervated caudate nucleus. This study was designed to investigate the role of inflammatory cells in injury-induced recovery. A hemiparkinsonian syndrome was induced in rats by unilateral injections of 6-hydroxydopamine into the pars compacta of the substantia nigra. Phytohemagglutinin-stimulated rat peritoneal cells, predominantly T cells and macrophages, were stereotactically implanted in the lesioned caudate-putamen, and amphetamine-induced turning was used to assess recovery. Animals receiving implants of activated peritoneal cells showed a 47% decrease in amphetamine-induced turning 8 weeks after implantation, which was not seen in control or sham-operated animals. Immunocytochemistry revealed increased tyrosine hydroxylase reactive fibers in the leukocyte-implanted striatum. We conclude that implantation of activated leukocytes promotes functional recovery in hemiparkinsonian rats.
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PMID:Recovery in hemiparkinsonian rats following intrastriatal implantation of activated leukocytes. 151 12

Tyrosine hydroxylase immunohistochemical analysis was performed on tissue sections through the pallidal complex from Nemistrina monkeys which had been made hemi-parkinsonian by intracarotid MPTP infusion 8-12 months earlier. The side contralateral to the MPTP infusion showed a dense dopaminergic innervation of the pallidum (both internal and external segments), but particularly the internal pallidum. The side of the brain ipsilateral to the MPTP infusion showed a remarkable sparing of the pallidal dopaminergic innervation, despite almost total loss of the dopaminergic innervation of the caudate and putamen. These results support the view that in the primate, the nigropallidal projection is mostly distinct from the nigrostriatal projection. It is also suggested that perhaps the sparing of pallidal dopamine at least in part may contribute to some of the recovery of function observed in some monkeys following exposure to MPTP.
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PMID:Relative sparing of the dopaminergic innervation of the globus pallidus in monkeys made hemi-parkinsonian by intracarotid MPTP infusion. 168 10

Following systemic injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), young (2-month-old) C57BL/6 mice show decreased dopaminergic (DA) nigrostriatal fibers and DA concentration in the striatum. We transplanted syngeneic, allogeneic and xenogeneic adrenal medullary grafts into the striatum of the MPTP-treated young 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 high performance liquid chromatography with electrochemical detection (LCEC). The grafted syngeneic adrenal chromaffin cells survived better than allogeneic or xenogeneic chromaffin cells, and host DA nigrostriatal fiber recovery was more prominent in mice with a syngeneic graft than in mice with an allogeneic or xenogeneic graft. However, the degree of host fiber recovery in mice with allogeneic or xenogeneic mice was greater than in mice with a sham operation alone, even though the allografts and xenografts had no surviving chromaffin cells. Allografts and xenografts showed prominent rejection responses, with T lymphocyte infiltration in addition to macrophages. We conclude that a syngeneic adrenal graft survives better than an adrenal allograft or xenograft and promotes recovery of the intrinsic host nigrostriatal DA fibers. We also conclude that grafted chromaffin cell survivability influences the degree of host DA fiber recovery following MPTP depletion. Adrenal medullary grafts to Parkinsonian patients are currently under way in a large number of hospitals; we suggest that greater attention be paid to methods which lead to enhanced survival of the grafted chromaffin cells, since survivability might be closely related to the functional recovery of these patients.
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PMID:The nigrostriatal dopaminergic system in MPTP-treated mice shows more prominent recovery by syngeneic adrenal medullary graft than by allogeneic or xenogeneic graft. 186 45

Fine structural correlates and functional parameters were measured in pinealectomized rats following grafting of the pineal gland into the third cerebral ventricle. Pinealectomy caused a significant decrease in serum melatonin concentration of animals compared to that in normal controls. No significant difference was observed in the serum melatonin concentration between pinealectomized rats and those receiving sham transplantation with fragments of occipital cortex. By 6 weeks nearly 50% of pinealectomized rats receiving pineal transplants demonstrated a significant increase in the serum melatonin concentration in contrast to that of pinealectomized rats and pinealectomized animals receiving sham transplants. Pinealocytes survived and flourished following transplantation from the epithalamic region to the third cerebral ventricle of the hypothalamus in host rats. These cells were found to be arranged individually or in clusters surrounding fenestrated capillaries of the graft. Moreover, these pinealocytes demonstrated ultrastructural features indicative of an active secretory process, including dense-core and clear vesicles as well as vacuoles containing flocculent material. Additional characteristics distinctive of normal control pinealocytes were observed in surviving cells of grafts, such as synaptic ribbons, synaptic ribbon fields, and myeloid bodies. Bundles of unmyelinated axons and apparent adrenergic nerve endings were observed with transmission electron microscopy and immunocystochemistry using antisera against tyrosine hydroxylase (TH). Nerve fibers and terminals were found within perivascular spaces surrounding fenestrated capillaries of viable grafts. These reported observations suggest that a significant population of transplanted pinealocytes recover functional activity (e.g., heightened melatonin secretion) following stereotaxic grafting into the third cerebral ventricles of pinealectomized animals. This apparent recovery of function may be linked directly to reinnervation of the gland by nerve fibers that appear to arise from the underlying median eminence.
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PMID:Transplantation of the pineal gland in the mammalian third cerebral ventricle. 196 56

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

Previous neural grafting studies have shown that embryonic dopamine neurons survive transplantation into the parenchyma of the brain; however, fiber outgrowth from those cells is often limited to the immediate vicinity of the graft. More extensive outgrowth is desirable for promoting and maintaining functional recovery of damaged neural systems in animal models as well as human neurodegenerative disorders. The present study examined the possibility of stimulating fiber outgrowth of grafted neurons by simultaneously grafting dopamine neurons with their embryonic target cells. Subsequent functional recovery was evaluated in concert with morphological characteristics of these grafts. Co-grafts of embryonic mesencephalic and striatal cells were implanted into the DA-denervated striatum of rats previously given unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway. Two types of co-grafts were implanted into the DA-denervated striatum: mixed or separate cell suspensions. Tyrosine hydroxylase immunocytochemical analysis of brain sections containing co-grafts revealed extensive arborization of TH-positive neurons in both types of co-grafts. When mesencephalic and striatal nerve cells were implanted into separate sites, TH-positive neurons extended projections that appeared to preferentially reach regions occupied by embryonic striatal neurons. Moreover, the average size of TH-positive cell bodies found in mixed or separate co-grafts was significantly larger than the size of those found in single mesencephalic grafts. Amphetamine-induced rotational behavior was used to assess the degree of functional recovery. In the majority of co-grafted animals, rotational behavior was attenuated by 3 weeks and reversed (amphetamine-induced contralateral rotation) by 5 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Embryonic mesencephalic and striatal co-grafts: development of grafted dopamine neurons and functional recovery. 237 55

GM1 ganglioside (GM1) has in the past been reported to promote regenerative sprouting and functional recovery in both central and peripheral nervous systems. The present experiments were performed in order to investigate whether GM1 might have any therapeutic effect on young mice who had been exposed to the Parkinson-producing neurotoxin MPTP. GM1 caused moderate to dramatic increases in striatal dopamine levels, depending upon duration of exposure to GM1, in animals previously exposed to MPTP. Furthermore, the effects of GM1 on enhancing striatal dopamine levels were apparent when GM1 administration was delayed until 3 days after the last MPTP injection was given and these effects were not reversed when GM1 was withdrawn. Tyrosine hydroxylase (TH) immunohistochemistry of the striatum demonstrated increased numbers of TH-positive fibers and TH-positive terminal fields in GM1-treated animals as compared to animals that received only MPTP. TH immunohistochemistry of the substantia nigra revealed little or no loss of parts compacta neurons in the MPTP-treated mice. On the basis of these observations, GM1 appears to increase the dopamine content of the striatum by promoting or stimulating regenerative sprouting of dopaminergic terminals and perhaps collateral sprouting from remaining intact fibers in the MPTP model of Parkinsonism in the young mouse. We suggest that GM1 ganglioside may hold some promise as a potential adjunct in the treatment of Parkinson's Disease.
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PMID:GM1 ganglioside treatment promotes recovery of striatal dopamine concentrations in the mouse model of MPTP-induced parkinsonism. 256 45

The effects of daily treatment with GM-1 ganglioside (30 mg/kg i.p.) or saline (1 ml/kg i.p.) in rats with discrete unilateral electrolytic lesions of the dorsal substantia nigra were investigated. Treatment with GM-1 ganglioside, beginning 3 days prior to surgery and continuing for 33 days post-operatively, caused reductions in the total ipsilateral turns and peak turning rates induced by apomorphine (0.75 mg/kg s.c.) between 7 and 31 days post-operatively, without altering the time course of the effect of apomorphine. No effects of GM-1 on lesion-induced changes in synaptosomal uptake of [3H]dopamine, dopamine, serotonin in the striatum or corresponding levels of metabolites were found. Treatment with GM-1 ganglioside had no effect on the rostrocaudal extent of the electrolytic lesion, but caused morphological changes at the site of the lesion, including a reduction in the density of glial cells. Treatment with GM-1 ganglioside resulted in a relative preservation of cell bodies, staining immunocytochemically for tyrosine hydroxylase, in the substantia nigra pars compacta (expressed as a percentage of the intact side), when compared with saline-treated rats. The results showed that GM-1 ganglioside promoted a partial functional recovery from apomorphine-induced circling, which may be due in part to a reduction in the extent of damage at the lesion site.
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PMID:Behavioural and morphological changes following treatment with GM-1 ganglioside of rats with an electrolytic lesion of the substantia nigra. 256 73


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