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)

Spasticity is an abnormal increase in muscle contraction often caused by damage to central motor pathways that control voluntary movement. During clinical examination, spasticity manifests as an increase in stretch reflexes, producing tendon jerks and resistance appearing as muscle tone. There are many causes of spasticity, including demyelination from multiple sclerosis, congenital damage from diseases such as cerebral palsy, trauma to the brain or spinal cord, hemorrhage or infarction, and other pathologic conditions that interrupt neural pathways. Effects of spasticity range from mild muscle stiffness to severe, painful muscle contractures and repetitive spasms that reduce mobility and substantially impede normal activities of daily living. Botulinum toxin therapy reduces spasticity and pain associated with several disorders. Local treatment with botulinum toxins can be used as adjunctive therapy, along with oral antispasticity medications, or alone to provide localized decrease in symptoms of spasticity and pain. Botulinum toxin therapy may be particularly useful for patients with spasticity due to stroke, whose treatment can be tailored based on recovery of function over time. In addition, botulinum toxin therapy is safe for pediatric patients, including children with cerebral palsy, who may not be able to tolerate the cognitive side effects of oral medications. Results of studies evaluating botulinum toxin for the treatment of spasticity due to various causes are presented here.
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PMID:Treatment of spasticity with botulinum toxin. 1256 67

Widespread demyelination and axonal loss are the pathological hallmarks of multiple sclerosis. The multifocal nature of this chronic inflammatory disease of the central nervous system complicates cellular therapy and puts emphasis on both the donor cell origin and the route of cell transplantation. We established syngenic adult neural stem cell cultures and injected them into an animal model of multiple sclerosis--experimental autoimmune encephalomyelitis (EAE) in the mouse--either intravenously or intracerebroventricularly. In both cases, significant numbers of donor cells entered into demyelinating areas of the central nervous system and differentiated into mature brain cells. Within these areas, oligodendrocyte progenitors markedly increased, with many of them being of donor origin and actively remyelinating axons. Furthermore, a significant reduction of astrogliosis and a marked decrease in the extent of demyelination and axonal loss were observed in transplanted animals. The functional impairment caused by EAE was almost abolished in transplanted mice, both clinically and neurophysiologically. Thus, adult neural precursor cells promote multifocal remyelination and functional recovery after intravenous or intrathecal injection in a chronic model of multiple sclerosis.
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PMID:Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. 1270 Jul 43

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

Chronic demyelination is a pathophysiologic component of compressive spinal cord injury (SCI) and a characteristic finding in demyelinating diseases including multiple sclerosis (MS). A better characterization of endogenous cells responsible for successful remyelination is essential for designing therapeutic strategies aimed at restoring functional myelin. The present study examined the spatiotemporal response of endogenous oligodendrocyte precursor cells (OPCs) following ethidium bromide (EB)-induced demyelination of the adult rat spinal cord. Beginning at 2 days post-EB injection (dpi), a robust mobilization of highly proliferative NG2(+) cells within the lesion was observed, none of which expressed the oligodendrocyte lineage-associated transcription factor Nkx2.2. At 7 dpi, a significant up-regulation of Nkx2.2 by OPCs within the lesion was observed, 90% of which coexpressed NG2 and virtually all of which coexpressed the bHLH transcription factor Olig2. Despite successful recruitment of Nkx2.2(+)/Olig2(+) OPCs within the lesion, demyelinated axons were not remyelinated by these OPCs in regions lacking astrocytes. Rather, Schwann cell remyelination predominated throughout the central core of the lesion, particularly around blood vessels. Oligodendrocyte remyelination was observed in the astrogliotic perimeter, suggesting a necessary role for astrocytes in oligodendrocyte maturation. In addition, reexpression of the radial glial antigen, RC-1, by reactive astrocytes and ependymal cells was observed following injury. However, these cells did not express the neural stem cell (NSC)-associated transcription factors Sox1 or Sox2, suggesting that the endogenous response is primarily mediated by glial progenitors. In vivo electrophysiology demonstrated a limited and unsustained functional recovery concurrent with endogenous remyelination following EB-induced lesions.
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PMID:Endogenous Nkx2.2+/Olig2+ oligodendrocyte precursor cells fail to remyelinate the demyelinated adult rat spinal cord in the absence of astrocytes. 1569 15

The aim of this outcome study was to evaluate the effectiveness and prognostic factors of inpatient multidisciplinary rehabilitation treatment in patients with multiple sclerosis (MS). We analysed 230 consecutive inpatients with MS admitted to an MS rehabilitation ward who followed an individualized, goal-oriented, multidisciplinary rehabilitation program. Every patient was submitted to a neurological examination and evaluated by means of Kurtzke's Expanded Disability Status Scale (EDSS), with its functional systems (FS), Barthel Index (BI) and the Rivermead Mobility Index (RMI). We observed an effectiveness (percentage of potential improvement achieved during rehabilitation) of nearly 16% on BI and 8% on RMI, corresponding to an improvement in 124 patients (54%) on BI and 113 patients (49%) on RMI. Basal EDSS (beta = -0.32, P <0.001), cognitive status (beta = -0.15, P <0.05) and disease duration (beta = -0.13, P <0.05) were negatively associated with effectiveness of treatment on BI (adjusted R2 = 0.176), whereas effectiveness on RMI was correlated only with the EDSS score (beta = -0.34, P <0.001, adjusted R2 = 0.113). In the logistic regression analysis, the absence of severe sphincteric disturbances was correlated with the probability of improvement on BI that was nearly twice as high (OR =2.25, 95% CI 1.24-4.08) as that of other patients. Moreover, patients without severe cognitive deficits showed a similar probability (OR =2.37, 95% CI 1.05-5.33) of improvement on RMI. The results of this study provide further evidence that intensive multidisciplinary rehabilitation in MS is effective in the majority of MS patients and that early treatment may favour functional recovery.
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PMID:Prognostic factors in multidisciplinary rehabilitation treatment in multiple sclerosis: an outcome study. 1632 Jul 34

Functional magnetic resonance imaging (fMRI) is being widely used to study recovery of function in patients with several neurological conditions, including multiple sclerosis, stroke and Alzheimer's disease. The application of this MR technique has shown that plastic cortical changes do occur after central nervous system (CNS) injury of different aetiology, that such changes are related to the extent of CNS damage and that they can contribute in limiting the clinical consequences of brain damage. Conversely, the failure or exhaustion of the adaptive properties of the cerebral cortex might be among the factors responsible for the accumulation of 'fixed' neurological deficits. New studies aimed at investigating the effect of therapies devoted to promote brain plasticity are now warranted.
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PMID:Functional MRI to study brain plasticity in clinical neurology. 1670 77

Cortical reorganization has been demonstrated during performance of a motor task in patients with multiple sclerosis. Converging evidence suggests that changes in gray matter volume represent an early hallmark of the disease. We used functional MRI to investigate the role of cortical adaptive mechanisms in maintaining visuo-motor function in the face of structural damage. Two cohorts of patients with clinically definite relapsing-remitting multiple sclerosis were compared with healthy controls matched for demographic, motor and cognitive characteristics during the performance of a visuo-motor integration task. Direct comparison between the two groups demonstrated a greater response of the contralateral dorsal premotor cortex and of the ipsilateral superior parietal cortex in relapsing-remitting multiple sclerosis patients. The functional MRI changes in these areas were strongly correlated with decreased gray matter volumes and increased lesion burden, respectively. Our study demonstrated a selective involvement of the parieto-premotor circuitry in a relatively early stage of the disease, which was not influenced by clinical, motor or cognitive variables. Moreover these results confirm the potential for functional recovery and the adaptive role of these areas in the motor reorganization of multiple sclerosis patients.
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PMID:Adaptive cortical changes and the functional correlates of visuo-motor integration in relapsing-remitting multiple sclerosis. 1671 25

Patients with multiple sclerosis (MS) can exhibit an exceptionally wide variety of symptoms. This is largely due to the semi-random distribution of the lesions in the central nervous system (CNS). Most lesions occur in apparently "silent" areas in the brain, and so cause no detectable symptoms. The disease is therefore much more active than a mere clinical monitoring would suggest. Most symptoms are related to a loss of function. During the relapses, this is due to a failure of axonal conduction at the site of the lesion(s). The conduction block is caused by the local demyelination which prevents the saltatory conduction but also seemingly, to some extend, by the inflammation per se. Remissions are related to a recovery of function of the affected axons owing to a spreading of sodium channels along the demyelinated axolemma but also to cerebral functional plasticity and remyelination. However, nerve conduction remains slower and less secure than normal, easily altered by physico-chemical changes such as the increase in body temperature (Uhthoff's phenomenon). Remission is incomplete when the lesion has led to axonal transaction and therefore axonal loss. Progression in MS is mainly related to "slow-burning" diffuse and chronic axonal loss in a toxic inflammatory milieu. Lastly, some symptoms in MS are so-called "positive" arising from an acquired hyperexcitability of demyelinated axons and occur either spontaneously (e.g. paresthesias) or mechanically (e.g. Lhermitte's sign).
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PMID:[Pathophysiology of multiple sclerosis]. 1694 17

Pain therapeutics discovered by molecular mining of the expressed genome of Australian predatory cone snails are providing lead compounds for the treatment of neurological diseases such as multiple sclerosis, shingles, diabetic neuropathy and other painful neurological conditions. The high specificity exhibited by these novel compounds for neuronal receptors and ion channels in the brain and nervous system indicates the high degree of selectivity that this class of neuropeptides can be expected to show when used therapeutically in humans. A lead compound, ACV1 (conotoxin Vc1.1 from Conus victoriae), has entered Phase II clinical trials and is being developed for the treatment for neuropathic pain. ACV1 will be targeted initially for the treatment of sciatica, shingles and diabetic neuropathy. The compound is a 16 amino acid peptide [Sandall et al., 2003. A novel alpha-conotoxin identified by gene sequencing is active in suppressing the vascular response to selective stimulation of sensory nerves in vivo. Biochemistry 42, 6904-6911], an antagonist of neuronal nicotinic acetylcholine receptors. It has potent analgesic activity following subcutaneous or intramuscular administration in several preclinical animal models of human neuropathic pain [Satkunanathan et al., 2005. Alpha conotoxin Vc1.1 alleviates neuropathic pain and accelerates functional recovery of injured neurons. Brain. Res. 1059, 149-158]. ACV1 may act as an analgesic by decreasing ectopic excitation in sensory nerves. In addition ACV1 appears to accelerate the recovery of injured nerves and tissues.
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PMID:Therapeutic applications of conotoxins that target the neuronal nicotinic acetylcholine receptor. 1697 78

Since the discovery of adult neural stem cells, mobilization of endogenous stem cells from the subventricular zone (SVZ) emerges as a promising strategy to promote brain repair. Here, we examined the effect of environment enrichment on SVZ cell mobilization in demyelinating pathologies. We showed that enriched housing conditions reduced functional impairment in experimental autoimmune encephalomyelitis (EAE), a rodent model of multiple sclerosis. Furthermore, both in a focal demyelination model (lysolecithin injection) and in the inflammatory EAE model, SVZ mitotic activity and the number of SVZ-derived cells in demyelinated areas were significantly increased by environment enrichment. Enriched housing conditions also promoted the oligodendrocyte fate of SVZ-recruited cells in the EAE lesions. Altogether our results show that environment enrichment provides beneficial conditions to promote the mobilization of neural progenitors into demyelinating lesions and to favour functional recovery.
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PMID:Enriched environment promotes adult neural progenitor cell mobilization in mouse demyelination models. 1729


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