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 effect of unilateral labyrinthectomy followed by the process of vestibular compensation on the incorporation of radioactive phosphate into frog brain proteins was investigated. Phosphoproteins were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography. The present data show that unilateral labyrinthectomy affects the incorporation of 32P into various frog brain proteins. In particular, the phosphorylation of a 20-kDa protein appeared enhanced during early stages of vestibular compensation (4-12 days). This 20-kDa protein was shown to be immunologically related to myelin basic protein and its phosphorylation was regulated by an endogenous calcium/calmodulin-dependent protein kinase. These data might indicate that in addition to neuronal components, components of glial origin are also involved in biochemical events that lead to functional recovery after neuronal lesions.
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PMID:Vestibular compensation affects endogenous phosphorylation of frog brain proteins. 137 81

Trophic control over the expression and membrane distribution of voltage-dependent ion channels is one of the principal organizing events underlying the maturation of excitable cells. The myelin sheath is a major structural determinant of regional ion channel topography in central axons, but the exact molecular signals that mediate local interactions between the oligodendrocyte and axolemma are not known. We have found that large caliber fibre pathways in the brain of the mutant mouse shiverer (shi, gene on chromosome 18), whose developmental fate of myelination is averted by deletion of five exons in the myelin basic protein gene, have a striking excess of sodium channels. As cytoplasmic membranes of shiverer oligodendroglia still adhere to axons, the evidence indicates that myelin basic protein or a myelin basic protein-dependent glial transmembrane signal associated with compact myelin formation, rather than a simple glial-axon contact inhibition or an intrinsic genetic program of neuronal differentiation, could be critical in downregulating sodium channel density in axons. Here we use the shiverer mutant to show that mature central nervous system projection neurons with large caliber unmyelinated fibres sustain functional excitability by increasing sodium channel density. This axon plasticity, triggered by the absence of a single glial protein, contributes to the unexpectedly mild degree of neurological impairment in the mutant brain without myelin, and may be a potentially inducible mechanism determining the recovery of function from dysmyelinating disease.
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PMID:Sodium channel density in hypomyelinated brain increased by myelin basic protein gene deletion. 171 50

Neonatal periventricular white matter injury is a major contributor to chronic neurologic dysfunction. In a neonatal rat stroke model, myelin basic protein (MBP) immunostaining reveals acute periventricular white matter injury. Yet, the extent to which myelin proteins can recover after neonatal hypoxic-ischemic injury is unknown. We developed a quantitative method to correlate the severity of the hypoxic-ischemic insult with the magnitude of loss of MBP immunostaining. Seven-day-old (P7) rats underwent right carotid ligation, followed by exposure to 8% oxygen for 1, 1.5, 2, or 2.5 h. On both P12 and P21, white matter integrity was evaluated by densitometric analysis of MBP immunostaining, and the amount of tissue injury was evaluated by morphometric measurements of cerebral hemisphere areas. The most severe hypoxic-ischemic insults (2.5 h) elicited marked reductions in MBP immunostaining ipsilaterally on both P12 and P21. In contrast, in mildly lesioned animals (1.5 h), MBP immunostaining was reduced ipsilaterally on P12, but 2 wk after lesioning, on P21, there was a substantial restoration of MBP immunostaining. The restoration in MBP immunostaining could reflect either functional recovery of injured oligodendroglia or proliferation and maturation of oligodendroglial precursors. Our data demonstrate that quantitative measurement of MBP immunostaining provides a sensitive indicator of acute oligodendroglial injury. Most importantly, we show that in this neonatal rodent stroke model, restoration of myelin proteins occurs after moderate, but not after more severe, cerebral hypoxia-ischemia.
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PMID:Hypoxic-ischemic oligodendroglial injury in neonatal rat brain. 1175 36

Neurotrophins enhance the survival of cells in the nervous system under both physiological and pathological conditions, such as those caused by disease or trauma. We recently demonstrated that expression of brain-derived neurotrophic factor (BDNF) was up-regulated in neurons and glia after compression-induced spinal cord injury (SCI). We show here the effects of BDNF on the oligodendrocyte survival and functional recovery after SCI. The effects of intrathecally administered BDNF on both Cu/Zn superoxide dismutase (CuZnSOD) and myelin basic protein (MBP) expression were examined using rats that had received compression-induced spinal cord injury. CuZnSOD expression in the spinal cord was down-regulated within 24 h of compression-induced injury and then recovered. Continuous infusion of BDNF inhibited the acute down-regulation of CuZnSOD expression. In situ hybridization showed that CuZnSOD was expressed in both neurons and glia. Although MBP expression was greatly reduced after injury, BDNF administration promoted the recovery of MBP expression nearly to a control level after 2 wk. Furthermore, BDNF administration also prompted behavioral recovery. These results suggest BDNF's usefulness in human clinical applications. The attenuation of CuZnSOD down-regulation may be related to a protective effect of BDNF and the promotion of MBP up-regulation may be related to a long-lasting restorative effect.
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PMID:Effects of brain-derived neurotrophic factor (BDNF) on compression-induced spinal cord injury: BDNF attenuates down-regulation of superoxide dismutase expression and promotes up-regulation of myelin basic protein expression. 1185 17

Lymphocytes respond to myelin proteins after spinal cord injury (SCI) and may contribute to post-traumatic secondary degeneration. However, there is increasing evidence that autoreactive T-lymphocytes may also convey neuroprotection and promote functional recovery after CNS injury. To clarify the role of myelin autoreactive lymphocytes after SCI, we performed contusion injuries in the thoracic spinal cord of transgenic (Tg) mice in which >95% of all CD4+ T-lymphocytes are reactive with myelin basic protein (MBP). We observed significantly impaired recovery of locomotor and reflex function in Tg mice compared with non-Tg (nTg) littermates. Measures of functional impairment in Tg mice correlated with significantly less white matter at the injury site, and morphometric comparisons of injured Tg and nTg spinal cords revealed increased rostrocaudal lesion expansion (i.e., secondary degeneration) in Tg mice. Rostrocaudal to the impact site in SCI-nTg mice, demyelination was restricted to the dorsal funiculus, i.e., axons undergoing Wallerian degeneration. The remaining white matter appeared normal. In contrast, lymphocytes were colocalized with regions of demyelination and axon loss throughout the white matter of SCI-Tg mice. Impaired neurological function and exacerbated neuropathology in SCI-Tg mice were associated with increased intraspinal production of proinflammatory cytokine mRNA; neurotrophin mRNA was not elevated. These data suggest that endogenous MBP-reactive lymphocytes, activated by traumatic SCI, can contribute to tissue injury and impair functional recovery. Any neuroprotection afforded by myelin-reactive T-cells is likely to be an indirect effect mediated by other non-CNS-reactive lymphocytes. Similar to the Tg mice in this study, a subset of humans that are genetically predisposed to autoimmune diseases of the CNS may be adversely affected by vaccine therapies designed to boost autoreactive lymphocyte responses after CNS trauma. Consequently, the safe implementation of such therapies requires that future studies define the mechanisms that control T-cell function within the injured CNS.
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PMID:Pathological CNS autoimmune disease triggered by traumatic spinal cord injury: implications for autoimmune vaccine therapy. 1192 34

Injury-induced self-destructive processes cause significant functional loss after incomplete spinal cord injury (SCI). Cellular elements of both the innate (macrophage) and the adaptive (T-cell) immune response can, if properly activated and controlled, promote post-traumatic regrowth and protection after SCI. Dendritic cells (DCs) trigger activation of effector and regulatory T-cells, providing a link between the functions of the innate and the adaptive immune systems. They also initiate and control the body's response to pathogenic agents and regulate immune responses to both foreign and self-antigens. Here we show that post-injury injection of bone marrow-derived DCs pulsed with encephalitogenic or nonencephalitogenic peptides derived from myelin basic protein, when administered (either systemically or locally by injection into the lesion site) up to 12 d after the injury, led to significant and pronounced recovery from severe incomplete SCI. No significant protection was seen in DC recipients deprived of mature T-cells. Flow cytometry, RT-PCR, and proliferation assays indicated that the DCs prepared and used here were mature and immunogenic. Taken together, the results suggest that the DC-mediated neuroprotection was achieved via the induction of a systemic T-cell-dependent immune response. Better preservation of neural tissue and diminished formation of cysts and scar tissue accompanied the improved functional recovery in DC-treated rats. The use of antigen-specific DCs may represent an effective way to obtain, via transient induction of an autoimmune response, the maximal benefit of immune-mediated repair and maintenance as well as protection against self-destructive compounds.
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PMID:Vaccination with dendritic cells pulsed with peptides of myelin basic protein promotes functional recovery from spinal cord injury. 1450 81

Excitotoxic oligodendroglial death is one of the mechanisms which has been proposed to underlie demyelinating diseases of the CNS. We describe here functional consequences of excitotoxic lesions to the rabbit optic nerve by studying the visual evoked potentials (VEPs) measured in the visual cortex. Nerves were slowly infused with the excitotoxin kainate a subcutaneously implanted osmotic pump which delivered the toxin through a cannula onto the optic nerve. Records of VEPs were obtained before pump implantation and at 1, 3 and 7 days post-implantation, and weekly evaluated thereafter for up to 4 months. We observed that the VEPs generated by light stimuli progressively changed in both amplitude and profile after the lesion as well as in comparison to those generated in control animals infused with vehicle. Histological examination of the damage caused by the excitotoxic insult showed that large areas of the optic nerve were demyelinated and their axons distorted. These observations were confirmed and extended by immunohistochemical analyses using markers to neurofilaments, myelin basic protein and the oligodendrocyte marker APC. The results of the present paper indicate that the consequences of excitotoxicity in the optic nerve share functional and morphological alterations which are found in demyelinating disorders. In addition, this experimental paradigm may be useful to evaluate the functional recovery of demyelinated optic nerves following various repair strategies.
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PMID:Excitotoxic insults to the optic nerve alter visual evoked potentials. 1469 51

Spinal cords of adult cats were transected and subsequently reconnected with the biocompatible porous poly (N-[2-hydroxypropyl] methacrylamide) hydrogel, NeuroGel. Tissue repair was examined at various time points from 6-21 months post reconstructive surgery. We examined two typical phenomena, astrogliosis and scar formation, in spines reconstructed with the gel and compared them to those from transected non-reconstructed spines. Confocal examination with double immunostaining for glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) showed that the interface formed between the hydrogel and the spine stumps did prevent scar formation and only a moderate gliosis was observed. The gel implant provided an adequate environment for growth of myelinated fibers and we saw angiogenesis within the gel. Electron microscopy showed that regenerating axons were myelinated by Schwann cells rather than oligodendrocytes. Moreover, the presence of the gel implant lead to a considerable reduction in damage to distal caudal portions of the spine as assessed by the presence of more intact myelinated fibers and a reduction of myelin degradation. Neurologic assessments of hindlimb movement at various times confirmed that spinal cord reconstruction was not only structural but also functional. We conclude that NeuroGel lead to functional recovery by providing a favorable substrate for regeneration of transected spinal cord, reducing glial scar formation and allowing angiogenesis.
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PMID:Prevention of gliotic scar formation by NeuroGel allows partial endogenous repair of transected cat spinal cord. 1470 47

Oligodendrocyte precursor cells require exogenous neurotrophin-3 (NT-3) for differentiation into oligodendrocytes. We transfected precursor cells with the gene for NT-3 and looked for changes in their development into myelin-forming cells. The expression of NT-3 in transfected cells was demonstrated by reverse transcription followed by PCR as well as by Northern blots. Direct synthesis of the neurotrophin product and its release to the culture supernatants were also shown by specific ELISA. Transfection converts precursor cells into actively dividing cells that can incorporate 3H-thymidine into DNA. In the absence of growth factors, a parallel increase in the survival of the transfected cultures was also demonstrated by the MTT test. The final demonstration of biological changes in transfected versus untreated cells was a 10-fold increase in myelin basic protein production observed in Western blots and the direct observation by phase-contrast and electron microscopy of myelin membranes in cocultures with hippocampal neurons. We discuss the future use of this transfected cells in regeneration and functional recovery in experimental models of multiple sclerosis.
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PMID:In vitro myelination by oligodendrocyte precursor cells transfected with the neurotrophin-3 gene. 1513 15

Compressive neuropathies are highly prevalent, debilitating conditions with variable functional recovery after surgical decompression. Chronic nerve compression injury induces concurrent Schwann cell proliferation and apoptosis in the early stages of the disorder, independent of axonal injury. These proliferating Schwann cells locally demyelinate and remyelinate in the region of injury. Furthermore, Schwann cells upregulate vascular endothelial growth factor secondary to chronic nerve compression injury and induce neovascularization to facilitate the recruitment of macrophages. In contrast to Wallerian degeneration, macrophage recruitment occurs gradually with chronic nerve compression injury and continues for a longer time. Schwann cells change their gene and protein expression in response to mechanical stimuli as shear stress decreases the expression of myelin associated glycoprotein and myelin basic protein mRNA and protein for in vitro promyelinating Schwann cells. The local down-regulation of myelin associated glycoprotein in the region of compression injury creates an environment allowing axonal sprouting that may be reversed with intraneural injections of purified myelin associated glycoprotein. These studies suggest that while the reciprocal relationship between neurons and glial cells is maintained, chronic nerve compression injury is a Schwann cell-mediated disease.
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PMID:Understanding the biology of compressive neuropathies. 1599 49


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