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)

A fundamental issue in central nervous system development regards the effect of target tissue on the differentiation of innervating neurons. We address this issue by characterizing the role the retinal ganglion cell target, i.e., the optic tectum, plays in regulating expression of tubulin and nicotinic acetylcholine receptor genes in regenerating retinal ganglion cells. Tubulins are involved in axonal growth, whereas nicotinic acetylcholine receptors mediate communication across synapses. Retinal ganglion cell axons were induced to regenerate by crushing the optic nerve. Following crush, there was a rapid increase in alpha-tubulin RNAs (3 days), which preceded the increase in nicotinic acetylcholine receptor RNAs (10-15 days). Both classes of RNAs approached control levels by the time retinotectal synapses and functional recovery were restored (4-6 weeks). If the optic nerve was repeatedly crushed or its target ablated, tubulin RNAs remained elevated, and the increase in receptor RNAs that would otherwise be seen 2 weeks after a single nerve crush did not occur. The interaction of retinal ganglion cell axons with their targets in the optic tectum appears, then, to exert a suppressive effect on the RNA encoding a cytoskeletal protein, tubulin, and an inductive effect on RNAs encoding nicotinic acetylcholine receptors involved in synaptic communication.
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PMID:Target-dependent regulation of retinal nicotinic acetylcholine receptor and tubulin RNAs during optic nerve regeneration in goldfish. 137 Nov 43

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

Thirty-four children who sustained moderate to severe closed head injury underwent magnetic resonance imaging (MRI). Eight (24%) had MRI evidence of corpus callosum injury, most commonly within the posterior body and splenium. In contradistinction to reports in adults, there was no definite relationship between callosal injury and lower initial Glasgow Coma Scale scores, nor was there a significantly higher incidence of primary brain-stem lesions, diffuse axonal shear injury or intraventricular hemorrhage. In none of these 8 children did the initial admission computed tomography show evidence of callosal injury. Callosal injuries on MRI are not necessarily a poor prognostic finding, the majority of the 8 children showing good functional recovery.
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PMID:Corpus callosum lesions after closed head injury in children: MRI, clinical features and outcome. 140 15

There is clinical and experimental evidence that monoamine neurons respond to lesions with a wide range of compensatory adaptations aimed at preserving their functional integrity. Neurotoxin-induced lesions are followed by increased synthesis and release of transmitter from residual monoamine fibers and by axonal sprouting. However, the fate of lesioned neurons after long survival periods remains largely unknown. Whether regenerative sprouting may contribute significantly to recovery of function following lesions which induce cell loss has been questioned. We have previously analyzed the response of locus coeruleus (LC) neurons to systemic administration of the noradrenergic (NE) neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) to adult rats. This drug causes ablation of nearly all LC axon terminals within 2 weeks after administration, followed by a profound loss of LC cell bodies 6 months later. The present study was conducted to determine the fate of surviving LC neurons and to characterize their potential for regenerative sprouting during a 16 month period after DSP-4 treatment. The time-course and extent of LC neuron degeneration were analyzed quantitatively in Nissl-stained sections, and the regenerative response of residual neurons was characterized by dopamine-beta-hydroxylase immunohistochemistry. The results document that LC neurons degenerate gradually after DSP-4 treatment, cell loss reaching on average 57% after 1 year. LC neurons which survive the lesion exhibit a vigorous regenerative response, even in those animals in which cell loss exceeds 60-70%. This regenerative process leads progressively to restoration of the NE innervation pattern in the forebrain, with some regions becoming markedly hyperinnervated. In stark contrast to the forebrain, very little reinnervation takes place in the brainstem, cerebellum and spinal cord. These findings suggest that regenerative sprouting of residual neurons is an important compensatory mechanism by which the LC may regain much of its functional integrity in the presence of extensive cell loss. Furthermore, regeneration of LC axons after DSP-4 treatment is region-specific, suggesting that the pattern of reinnervation is controlled by target areas. Elucidation of the factors underlying recovery of LC neurons after DSP-4 treatment may provide insights into the compensatory mechanisms of central neurons after injury and in disease states.
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PMID:Restoration of ascending noradrenergic projections by residual locus coeruleus neurons: compensatory response to neurotoxin-induced cell death in the adult rat brain. 150 78

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

Research involving nerve transplantation has shown that tissue rejection limits the neurologic recovery unless the host is immunosuppressed. This study investigates an alternative to permanent or temporary immunosuppression using a rat model with nerve transplants from Brown-Norway rat donors to bridge defects in the sciatic nerve of Lewis rat recipients as these two inbred strains differ at both major and minor histocompatibility loci. The specific aim of this study was to evaluate if predegenerated nerve grafts decreased the tissue rejection and improved the neurologic recovery of animals with allogenic nerve grafts to avoid the problems associated with either short- or long-term immunosuppression. The animals in the experimental groups received cyclosporin-A, predegenerated grafts, both, or neither. The predegenerated grafts were produced by division of the nerve three weeks prior to grafting to allow for Wallerian degeneration to occur. The outcome was assessed by measurements stressing functional recovery (sensory testing, gait analysis, joint flexion contracture), studies of muscle recovery (muscle weight and hydroxyproline concentration), and histologic studies (axonal counts and inflammatory reaction). The animals receiving the predegenerated grafts without cyclosporin did have an improved recovery (joint flexion contracture 35 degrees +/- 8 degrees and hydroxyproline ratio 1.52 +/- 0.16) as compared to the joint flexion contractures and hydroxyproline ratios of the allograft group of animals without either cyclosporin-A or pretreatment and the ungrafted control group (47 degrees +/- 18 degrees, 1.68 +/- 0.34, and 53 degrees +/- 15 degrees, 4.50 +/- 0.27, respectively, p less than 0.01). However, all the isograft groups and allograft groups with cyclosporin-A, regardless of whether the graft had been predegenerated or not, had greater neurologic recovery than the allograft group with predegenerated grafts but without cyclosporin-A by the same parameters (p less than 0.01). Allograft groups with short-term immunosuppression with cyclosporin-A did as well as isograft groups, and isograft groups with predegenerated grafts did not do any better than isografts without pretreatment (p less than 0.01).
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PMID:Peripheral nerve transplantation: the effects of predegenerated grafts and immunosuppression. 157 98

Spermine, a polyamine, is known to enhance motor functional recovery after a sciatic nerve lesion in the rat. The effect of spermine on the sensory axonal elongation after a sciatic crush was studied with the pinch-test from the sural nerve in the rat. The effect of spermidine, another polyamine, on the motor functional recovery after a trauma was studied by using the toe-spreading ability as an indicator of motor recovery after a sciatic crush in the rat. Spermine enhanced the rate of regeneration of the sensory axons by 16%. Spermidine enhanced the rate of the motor recovery by 30%. These results suggest that not only spermine but also spermidine enhance regeneration of peripheral somatic nerves.
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PMID:Polyamines enhance recovery after sciatic nerve trauma in the rat. 157 87

We have previously demonstrated that systemic administration of testosterone accelerates functional recovery, as measured behaviorally, from facial paralysis induced by facial nerve crush axotomy in gonadectomized adult male hamsters. In this investigation, the hypothesis that testosterone enhances return of motor function by increasing the rate of axonal regeneration following injury was tested using fast axonal transport of radioactively labeled proteins to assess facial nerve regeneration. Adult castrated and intact males, and intact females, were subjected to right facial nerve crush axotomy at the stylomastoid foramen. One-half of the axotomized animals in each group received subcutaneous implants of testosterone, with the remainder of the animals sham implanted. Systemic administration of testosterone resulted in a 26-30% increase in the rate of regeneration of the fastest growing population of axons in the male experimental groups, regardless of whether the animal was castrated or not. This rate increase is similar to that observed in the conditioning lesion paradigm utilized by others. In the females, testosterone had a significant, but less pronounced, effect on the rate of axonal regeneration, which may be due in part to inherent gender-related differences in regenerative properties of facial motoneurons. A surprising finding of this study was that no shortening of the delay of sprout formation by testosterone was observed across the various experimental groups. These data suggest that the mechanism by which gonadal steroids act in the injured nervous system is partly through the differential regulation of the regenerative properties of the injured cell, presumably via hormone receptor-mediated action at the level of the neuronal genome.
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PMID:Testosterone differentially regulates the regenerative properties of injured hamster facial motoneurons. 174 96

Intramuscular injections of botulinum toxin type A (Oculinum) is used to treat strabismus and focal dystonias affecting orofacial muscles. However, the toxin-induced morphological changes that underlie the therapeutic alterations of tone in the muscles of mastication have not been described. In this study, paired intramuscular injections of botulinum toxin (10 units) were made in three adult monkeys (Macaca fascicularis) allowed to survive 14, 28 and 63 days. Another monkey received multiple injection-pairs over 84 days. Animals were killed by deep pentobarbital anaesthesia before transcardiac perfusion-fixation. Tissue sampled from comparable regions of the injected masseter, the uninjected masseter and an uninjected animal was processed for ultrastructural analysis. Few changes were found 14 days post-injection. However, muscle fibres showed myofibrillar dissolution, aberrations in the Z-line, and enlarged mitochondria in the region of the I-band by 28 days. In the 63-day and 84-day animals, the injected muscle was considerably smaller than the uninjected, contralateral muscle. Regions of the injected muscle contained fibres with markedly reduced cross-sectional area. Internalization of myonuclei, loss of myofibrillar organization, and helical complexes were common. Toxin-induced changes, though similar to those that follow denervation by axotomy, were not accompanied by degeneration of neuromuscular junctions. Instead, morphological evidence for axonal sprouting in the region of the neuromuscular junction, possibly contributing to functional recovery, was seen as early as 14 days in toxin-treated muscles.
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PMID:Ultrastructural changes in the masseter muscle of Macaca fascicularis resulting from intramuscular injections of botulinum toxin type A. 176 79

Deafferentation of certain brain regions in adult animals results in (1) the disappearance of degenerating axon terminals and (2) in the temporary persistence of vacant postsynaptic sites. These postsynaptic sites were shown to be re-supplied by sprouted axon terminals of intact axons. It is described in this paper, that in brain regions (e.g. cerebellar cortex, lateral geniculate nucleus) where axonal sprouting of local elements or of persisting afferent axons is negligible or absent, synaptic reorganization occurs via the active participation of postsynaptic dendritic and somatic elements of surviving local nerve cells. The dendrites may develop two types of reaction upon deafferentation (1) formation of presynaptic specializations along their otherwise "classical" postsynaptic membrane, resulting in the formation of new, dendro-dendritic synapses and (2) the "adaptive" (structural) reduction in size of denervated nerve cell dendritic arbor, leading to a relative increase in density of the surviving (though non-sprouting) afferent axon terminals. A partial functional recovery in both cases is also demonstrated.
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PMID:Morphological plasticity of dendrites in adult brain. 213 Jun 32


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