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)

The serotonin neurotoxin, 5,6-dihydroxytryptamine (5,6-DHT), was injected into the body cavity of snails. Changes induced in the central nervous system (CNS) by the neurotoxin were studied by morphological, electrophysiological and biochemical techniques for up to 90 days following injection. The neurotoxin induced a variety of ultrastructural alterations during the early phase (1st to 6th days) following treatment. On day 6 after treatment, membranous structures first appeared in the synaptic-like areas and apparently migrated to cell bodies where they were detected by day 14. Their number increased with time. Neurotoxin-induced structural alterations were found in neuronal processes and cell bodies of the serotonergic metacerebral giant cells injected intracellularly with horseradish peroxidase and in serotonin immunoreactive axons. These findings suggest that the toxin-induced alterations are rather selective for the serotonin-containing neuronal elements. The neurotoxin decreased the concentration of 5-HT in and [3H]5-HT uptake into cerebral and pedal ganglia, with a maximum effect between the 3rd and 5th day following drug administration. 5-HT levels and 5-HT uptake returned to normal by 19-21 days after treatment. The concentration of dopamine and of [3H]DA uptake capacity were reduced between 3-5 days after injection of 5,6-DHT by 6-7 days following treatment. The transmission from identified serotonergic synapses to targets was reduced beyond day 5 after 5,6-DHT administration. By 15 days after treatment, synaptic transmission between the metacerebral giant cell (MGC) and buccal followers was blocked. Transmission recovered by day 21 after 5,6-DHT. Comparison of the time-course of functional and structural recovery indicates that while functional recovery takes place within 21 days after treatment, certain structural alterations, e.g. the membranous structures and dense particles, remain in the nerve fibres and cell bodies. These may serve as specific intracellular markers of the serotonin-containing neuronal elements long after functional recovery from the effect of 5,6-DHT.
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PMID:Ultrastructural, biochemical and electrophysiological changes induced by 5,6-dihydroxytryptamine in the CNS of the snail Helix pomatia L. 132 60

In adult guinea pigs, the oculomotor nerve was sectioned proximally (at the tentorial edge) or more distally (at the orbital fissure) and immediately repaired by reapproximation. During a 24-week postoperative period, extrinsic eye motility was assessed by analyzing the vestibulo-ocular reflexes. The regenerated oculomotor nerve was studied morphometrically on semi-thin histological sections at 16 and 24 weeks postinjury. The selectivity of muscle reinnervation was investigated by injection of both single (horseradish peroxidase) and double (fluorescent dyes) retrograde axonal tracers into the eye muscles. Following proximal repair of the oculomotor nerve, the degree of recovery of extraocular motility varied among different animals and remained stable over long-term observations. In animals with poor recovery, aberrant eye movements were always found, and the somatotopic map of the reinnervated eye muscles was greatly altered. Distortions of the central representation were also seen in those animals in which a good level of functional recovery was seen. However, in animals with good recovery, a topographic bias was re-established by about 65% of the original neuronal population, as opposed to 26% in the animals with poor recovery. Neurons located contralateral to the axotomized nucleus sprouted intra-axially and projected their axons to denervated eye muscles. The number and diameter of the regenerated axons, the number and soma diameter of the axotomized neurons, and the ratio of distal axonal branches to proximal supporting neurons were all related to the degree of functional recovery. Following repair of the oculomotor nerve at the orbital fissure, extraocular motility had recovered in all of the animals at 16 weeks without aberrant phenomena. Functional regeneration of the distally transected oculomotor nerve is thought to be the result of selective muscle reinnervation.
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PMID:Experimental repair of the oculomotor nerve: the anatomical paradigms of functional regeneration. 140 21

Suture repair of cranial and peripheral nerves has reached a maximal level with the use of advanced microneurorrhaphy techniques; however, functional recovery of the repaired nerve is still often unsatisfactory due to misrouted axonal regrowth. Freeze-trimming the nerve ends prior to anastomosis has been shown to significantly improve fascicular alignment and subsequent functional recovery. This study assessed the feasibility of using laser energy to trim the nerve ends prior to suture anastomosis. The 302-nm excimer laser was used to trim the severed sciatic nerve ends prior to anastomosis in 28 rats. Scanning electron and light microscopy, horseradish peroxidase retrograde labeling, nerve conduction velocity, and functional recovery were assessed postoperatively. The excimer laser was able to trim the nerve ends flat thereby facilitating the coaptation and alignment of the nerve ends. Misrouting of axons occurred in both the laser-trim and control groups. Although this technique has theoretical advantages, no statistically significant improvement was demonstrated in this investigation. This may have been in part due to the small sample size, since a small increment of improvement was noted. It is possible, however, with continued refinements in technique that a functional improvement may be seen in subsequent studies.
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PMID:Laser-assisted nerve repair. Laser-trimming of nerve ends with epineurial suture anastomosis. 155 48

Following complete transection of the thoracic spinal cord at various times during embryonic development, chick embryos and posthatched animals exhibited various degrees of anatomical and functional recovery depending upon the age of injury. Transection on embryonic day 2 (E2), when neurogenesis is still occurring and before descending or ascending fiber tracts have formed, produced no noticeable behavioral or anatomical deficits. Embryos hatched on their own and were behaviorally indistinguishable from control hatchlings. Similar results were found following transection on E5, an age when neurogenesis is complete and when ascending and descending fiber tracts have begun to project through the thoracic region. Within 48 h following injury on E5, large numbers of nerve fibers were observed growing across the site of transection. By E8, injections of horse-radish peroxidase (HRP) administered caudal to the lesion, retrogradely labelled rostral spinal and brainstem neurons. Embryos transected on E5 were able to hatch and could stand and locomote posthatching in a manner that was indistinguishable from controls. Following spinal cord transections on E10, anatomical recovery of the spinal cord at the site of injury was not quite as complete as after E5 transection. Nonetheless, anatomical continuity was restored at the site of injury, axons projected across this region, and rostral spinal and brainstem neurons could be retrogradely labelled following HRP injections administered caudal to the lesion. At least part of this anatomical recovery may be mediated by the regeneration or regrowth of lesioned axons. Although none of the embryos transected on E10 that survived to hatching were able to hatch on their own, because several sham-operated embryos were also unable to hatch, we do not attribute this deficit to the spinal transection. When E10-transected embryos were aided in escaping from the shell, they were able to support their own weight, could stand, and locomote, and were generally comparable, behaviorally, to control hatchlings. Repair of the spinal cord following transection on E15 was considerably less complete compared to embryos transected on E2, E5, or E10. However, in some cases, a degree of anatomical continuity was eventually restored and a few spinal neurons rostral to the lesion could be retrogradely labelled with HRP. By contrast, labelled brainstem neurons were never observed following E15 transection. E15 transected embryos were never able to hatch on their own, and when aided in escaping from the shell, the hatchlings were never able to stand, support their own weight or locomote.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Anatomical and functional recovery following spinal cord transection in the chick embryo. 207 4

In this study we examined the effect of chronic GM-1 ganglioside treatment on the reestablishment of axonal continuity and functional recovery in spinal cord-transected rats. Previous studies have shown that chronic treatment with GM-1 ganglioside is effective in producing regeneration of lesioned mesostriatal dopaminergic neurons in the central nervous system [1, 2]. In addition, GM-1 ganglioside advances peripheral nerve regeneration following nerve crush injury [12]. Axonal continuity was determined by the ability of the spinal cord to transport horseradish peroxidase across the region of transection. Comparisons between ganglioside-treated and saline-treated controls showed that ganglioside treatment resulted in the reestablishment of axonal continuity between the spinal cord distal to the level of the transection and the brainstem. Saline-treated controls showed little evidence of axonal continuity between these two regions. Thus gangliosides induce reestablishment of axonal continuity and thereby could advance functional recovery in rats following spinal cord transection.
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PMID:Ganglioside-induced regeneration and reestablishment of axonal continuity in spinal cord-transected rats. 241 4

Corticorubral (CR) connections are reorganized after the red nucleus is deafferented by neonatal hemispherectomy. Our objective was to determine if the new decussating CR axons establish synaptic junctions with their target neurons. The ultrastructure of CR axonal terminal arbors was identified by the anterograde transport and histochemical labeling of wheat germ agglutinin lectin-bound horseradish peroxidase injected unilaterally into the pericruciate neocortex of adult cats that received unilateral neonatal hemispherectomy (HEMI cases) and normal adult cats (control cases). The regional organization of undecussated and decussated CR arbors was nearly equivalent in the HEMI cases. The fine structure of both connections was uniform. Asymmetrical synaptic junctions were observed in frequent axodendritic and infrequent axosomatic boutons en passage and boutons terminaux. The undecussated arbors formed the principal connection in the control cases. However, the fine structures of the decussated and undecussated arbors were comparable and matched the arrangements in the HEMI cases. We conclude that developmental deafferentation redirects CR axons to provide stable synaptic afferents to new targets. The reinnervation is homotypical in terms of regional and fine structure organization. It is likely to be an important factor in chemically mediated neurotransmission that contributes to the sparing/recovery of function after brain damage.
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PMID:Corticorubral connections: ultrastructural evidence for homotypical synaptic reinnervation after developmental deafferentation. 246 81

The present study sought to determine if axonal connectivity is established between 6-month-old neostriatal transplants and the host substantia nigra. Cell suspensions of fetal neostriatum were transplanted into the adult rat neostriatum lesioned previously by kainic acid. Horseradish peroxidase injections into the ipsilateral ventral midbrain labelled the lesion site and the intact neostriatum extensively, but no appreciable anterograde or retrograde label was found within the graft. These results demonstrate a paucity of connectivity between neostriatal grafts and the host brain at a time when other investigators have described transplant-mediated recovery of function.
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PMID:Minimal connectivity between six month neostriatal transplants and the host substantia nigra. 246 20

Previous reports from this laboratory have indicated that fetal rat striatal grafts have the major types of neuronal and glial components known to be involved in Huntington's chorea. In this study a number of major afferent and efferent innervations seen in normal striatum were examined in the striatal grafts and were compared with embryonic striatal afferents. First, using immunocytochemistry and histochemistry, the host serotonergic (5-HT), dopaminergic (DA, stained with anti-tyrosine hydroxylase (TH) antiserum), and acetylcholinesterase (AChE) fibers exhibited vigorous growth into the grafts implanted in neostriatum, lateral ventricle, globus pallidus or substantia nigra within a period of 6 and 10 weeks. Individual characteristic terminal patterns formed in striatal grafts: 5-HT fibers were diffused; TH fibers became heavily packed, and AChE fibers were patchy. This peculiar patternization of 5-HT and TH growth into striatal graft appeared to be a recapitulation of the normal 5-HT and TH ingrowth into striatum in the embryonic stage. However, a significantly slow (6 week) onset of adult 5-HT and TH ingrowth into the fetal graft was noted, as compared with that of normal embryonic development (5-6 days from the appearance of 5-HT and TH neurons). With the anterograde-transport marker Phaseolus vulgaris agglutinin leuca method, host cortical neurons also projected to the graft, but in limited numbers. Finally, with the retrograde-transport marker (horseradish peroxidase method, the grafts implanted in neostriatum were found incapable of sending fibers to a major, distal target, substantia nigra. In a current evaluation of striatal transplants, it is shown that major input to the graft can be achieved over time, but output to the distal nigra seems an unrealistic expectation. These data suggest that: (1) the fetal brain tissue was found to be a strong stimulant for sprouting or regeneration of adult nerve fibers; (2) a number of functional recoveries reported on the tested behavior paradigm in this grafting model could be due to the survival of striatal graft and the establishment of input circuitries; further, (3) the data illustrate the necessity of seeking a bridge from the striatal transplant to the host nigra. If a proper functional recovery in Huntington's chorea requires complete striatonigral circuitry, then such a bridge is worthy of a major investigation.
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PMID:Connectivities of the striatal grafts in adult rat brain: a rich afference and scant striatonigral efference. 259 10

In adult rats with a unilateral 6-hydroxydopamine-induced destruction of the nigrostriatal dopamine (DA) pathway, grafts of embryonic substantia nigra can establish a new dopaminergic terminal fiber plexus in the previously denervated neostriatum and compensate for some of the behavioral deficits induced by the nigrostriatal lesion. In the present study the synaptic connections of the ingrowing DA fibers from the graft were analyzed ultrastructurally, using immunocytochemical localization of tyrosine hydroxylase (TH), in animals whose lesion-induced motor asymmetry had been completely compensated for by the nigral grafts. In two of the animals, horseradish peroxidase-wheatgerm agglutinin conjugate was injected into the graft in order to trace possible reciprocal afferent connections to the graft from the host striatum. TH-immunoreactive axons from the graft were seen to make abundant symmetric synapses with neuronal elements in the host neostriatum. Between 85 and 90% of these synapses were on dendritic shafts and spines, and the rest were on neuronal perikarya. Two principal targets were identified: dendrites of spiny neurons, the majority of which are likely to be striatal projection neurons; and the cell bodies of giant neurons, most (or perhaps all) of which are known to be cholinergic interneurons. The synapses made on dendritic spines, which constituted about 40% of all TH-positive synapses formed by the TH-positive neurons in the graft, resembled those seen in normal animals, both in that they made contacts with spine necks and in that they invariably were associated with an asymmetric TH-negative synapse contacting the spine head. The innervation of the giant cell perikarya, which constituted about 6% of all TH-positive synapses found, was strikingly abnormal in that the graft-derived TH-positive fibers formed dense pericellular "baskets" selectively around the giant cell bodies. Such arrangements were never seen in the normal striatum, nor did they occur in the intact contralateral striatum in the grafted animals. It is proposed that this apparent dopaminergic hyperinnervation from the graft could provide a powerful inhibition of the cholinergic interneurons in the reinnervated host striatum, and that such an inhibitory mechanism could assist in the graft-induced functional recovery by potentiating the functional effects of DA synapses terminating on the spiny efferent neurons. This dual innervation may thus help to explain why restoration of only a small proportion of the striatal DA innervation by the graft is sufficient to induce complete compensation of, e.g., motor asymmetry in the lesioned rats.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Efferent synaptic connections of grafted dopaminergic neurons reinnervating the host neostriatum: a tyrosine hydroxylase immunocytochemical study. 285 78

Striatal kainic acid (KA) lesions induce behavioral and biochemical deficits which resemble symptoms encountered in patients suffering from Huntington's disease. In rats with KA lesions, fetal striatal transplants have shown to reverse the pervasive nocturnal hyperactivity induced by the lesion. In the present study 4.6 mm3 of fetal striatal tissue were delivered bilaterally into the anterodorsal portion of the lesioned caudate nucleus. Care was taken to deliver the transplant within the host parenchyma and away from the lateral ventricles. Locomotor behavior analyzed using the Digiscan animal activity monitors before and after the transplants demonstrated a reversal of the hyperactivity following transplants in 70% of lesioned animals. Microinjections of horseradish peroxidase delivered into the globus pallidus and substantia nigra of a small group of functionally recovered transplanted animals, did not reveal evidence for reinnervation between host nigra or pallidum and the transplant at 10 weeks post-transplantation. Other laboratories have reported anatomical connections by 6 months post-transplantation. Ventricular/brain ratios demonstrated that intraparenchymal transplants significantly reduced the ventricular dilation following KA lesion. These results suggest that functional recovery can be obtained when the transplant is immersed into the host's striatal parenchyma regardless of the existence of long-range anatomical connections.
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PMID:Intraparenchymal fetal striatal transplants and recovery in kainic acid lesioned rats. 296


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