Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0599766 (functional recovery)
 13,441 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sciatic nerves in adult male rats were transected and reunited via a silicone chamber. This was followed by a focal injection of recombinant ciliary neurotrophic factor (CNTF). To evaluate the effect of this therapeutic approach and to explore its possible mechanisms, nerve regeneration was traced by horseradish peroxidase retrograde labeling. Functional recovery was evaluated by functional assessment of the hind feet and the expression of a number of proteins was detected using immunohistochemistry. The results showed that a single administration of CNTF could promote regeneration of motor axons, with improved functional recovery in adult rats. Growth associated protein (GAP)-43, S100, CD68 and major histocompatibility complex class II immunoreactivity in the regenerative and distal nerves suggested that CNTF could promote axon regeneration, Schwann cell migration, monocyte infiltration and activation. CNTF might also indirectly promote axonal regeneration by further activating the JAK-STAT3 pathway and subsequently upregulating phosphotyrosine, GAP-43 and S100 expression to enhance proliferation, growth and migration of Schwann cells. CNTF has suggested important targets for pharmacological intervention in peripheral nerve disease and injury.
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PMID:Recombinant ciliary neurotrophic factor promotes nerve regeneration and induces gene expression in silicon tube-bridged transected sciatic nerves in adult rats. 1928 86

Surviving motoneurons undergo dendritic atrophy after spinal cord injury (SCI), suggesting an important therapeutic target for neuroprotective strategies to improve recovery of function after SCI. Our previous studies showed that phospholipase A2 (PLA2) may play an important role in the pathogenesis of SCI. In the present study, we investigated whether blocking cPLA2 pharmacologically with arachidonyl trifluoromethyl ketone (ATK) or genetically using cPLA2 knockout (KO) mice attenuates motoneuron atrophy following SCI. C57BL/6 mice received either sham or contusive SCI at the T10 level. At 30 min after SCI, mice were treated with ATK or vehicle. Four weeks later, motoneurons innervating the vastus lateralis muscle of the quadriceps were labeled with cholera toxin-conjugated horseradish peroxidase, and dendritic arbors were reconstructed in three dimensions. Soma volume, motoneuron number, lesion volume, and tissue sparing were also assessed, as were muscle weight, fiber cross-sectional area, and motor endplate size and density. ATK administration reduced percent lesion volume and increased percent volume of spared white matter compared to the vehicle-treated control animals. SCI with or without ATK treatment had no effect on the number or soma volume of quadriceps motoneurons. However, SCI resulted in a decrease in dendritic length of quadriceps motoneurons in untreated animals, and this decrease was completely prevented by treatment with ATK. Similarly, the vastus lateralis muscle weights of untreated SCI animals were smaller than those of sham-surgery controls, and these reductions were prevented by ATK treatment. No effects on fiber cross-sectional areas, motor endplate area or density were observed across treatment groups. Remarkably, genetically deleting cPLA2 in cPLA2 KO mice attenuated dendritic atrophy after SCI. These findings suggest that after SCI, cord tissue damage and regressive changes in motoneuron and muscle morphology can be reduced by inhibition of cPLA2, further supporting a role for cPLA2 as a neurotherapeutic target for SCI treatment.
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PMID:Inhibition of cPLA2 has neuroprotective effects on motoneuron and muscle atrophy following spinal cord injury. 2538 20

The present study aimed to evaluate the molecular mechanisms underlying combinatorial bone marrow stromal cell (BMSC) transplantation and chondroitinase ABC (Ch-ABC) therapy in a model of acellular nerve allograft (ANA) repair of the sciatic nerve gap in rats. Sprague Dawley rats (n=24) were used as nerve donors and Wistar rats (n=48) were randomly divided into the following groups: Group I, Dulbecco's modified Eagle's medium (DMEM) control group (ANA treated with DMEM only); Group II, Ch-ABC group (ANA treated with Ch-ABC only); Group III, BMSC group (ANA seeded with BMSCs only); Group IV, Ch-ABC + BMSCs group (Ch-ABC treated ANA then seeded with BMSCs). After 8 weeks, the expression of nerve growth factor, brain-derived neurotrophic factor and vascular endothelial growth factor in the regenerated tissues were detected by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Axonal regeneration, motor neuron protection and functional recovery were examined by immunohistochemistry, horseradish peroxidase retrograde neural tracing and electrophysiological and tibialis anterior muscle recovery analyses. It was observed that combination therapy enhances the growth response of the donor nerve locally as well as distally, at the level of the spinal cord motoneuron and the target muscle organ. This phenomenon is likely due to the propagation of retrograde and anterograde transport of growth signals sourced from the graft site. Collectively, growth improvement on the donor nerve, target muscle and motoneuron ultimately contribute to efficacious axonal regeneration and functional recovery. Thorough investigation of molecular peripheral nerve injury combinatorial strategies are required for the optimization of efficacious therapy and full functional recovery following ANA.
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PMID:Molecular examination of bone marrow stromal cells and chondroitinase ABC-assisted acellular nerve allograft for peripheral nerve regeneration. 2769 84

Transplanting embryonic precursors of GABAergic neurons from the medial ganglionic eminence (MGE) into adult mouse spinal cord ameliorates mechanical and thermal hypersensitivity in peripheral nerve injury models of neuropathic pain. Although Fos and transneuronal tracing studies strongly suggest that integration of MGE-derived neurons into host spinal cord circuits underlies recovery of function, the extent to which there is synaptic integration of the transplanted cells has not been established. Here, we used electron microscopic immunocytochemistry to assess directly integration of GFP-expressing MGE-derived neuronal precursors into dorsal horn circuitry in intact, adult mice with short- (5-6 weeks) or long-term (4-6 months) transplants. We detected GFP with pre-embedding avidin-biotin-peroxidase and GABA with post-embedding immunogold labeling. At short and long times post-transplant, we found host-derived synapses on GFP-immunoreactive MGE cells bodies and dendrites. The proportion of dendrites with synaptic input increased from 50% to 80% by 6 months. In all mice, MGE-derived terminals formed synapses with GFP-negative (host) cell bodies and dendrites and, unexpectedly, with some GFP-positive (i.e., MGE-derived) dendrites, possibly reflecting autoapses or cross talk among transplanted neurons. We also observed axoaxonic appositions between MGE and host terminals. Immunogold labeling for GABA confirmed that the transplanted cells were GABAergic and that some transplanted cells received an inhibitory GABAergic input. We conclude that transplanted MGE neurons retain their GABAergic phenotype and integrate dynamically into host-transplant synaptic circuits. Taken together with our previous electrophysiological analyses, we conclude that MGE cells are not GABA pumps, but alleviate pain and itch through synaptic release of GABA.
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PMID:Long-term, dynamic synaptic reorganization after GABAergic precursor cell transplantation into adult mouse spinal cord. 2913 56

After nerve-root avulsion injury of the brachial plexus, oxidative damage, inflammatory reaction, and glial scar formation can affect nerve regeneration and functional recovery. Melatonin (MT) has been shown to have good anti-inflammatory, antioxidant, and neuroprotective effects. Chondroitin sulfate ABC (ChABC) has been shown to metabolize chondroitin sulfate proteoglycans and can reduce colloidal scar formation. However, the effect of any of these drugs alone in the recovery of nerve function after injury is not completely satisfactory. Therefore, this experiment aimed to explore the effect and mechanism of combined application of melatonin and chondroitin sulfate ABC on nerve regeneration and functional recovery after nerve-root avulsion of the brachial plexus. Fifty-two Sprague-Dawley rats were selected and their C5-7 nerve roots were avulsed. Then, the C6 nerve roots were replanted to construct the brachial plexus nerve-root avulsion model. After successful modeling, the injured rats were randomly divided into four groups. The first group (injury) did not receive any drug treatment, but was treated with a pure gel-sponge carrier nerve-root implantation and an ethanol-saline solution via intraperitoneal (i.p.) injection. The second group (melatonin) was treated with melatonin via i.p. injection. The third group (chondroitin sulfate ABC) was treated with chondroitin sulfate ABC through local administration. The fourth group (melatonin + chondroitin sulfate ABC) was treated with melatonin through i.p. injection and chondroitin sulfate ABC through local administration. The upper limb Terzis grooming test was used 2-6 weeks after injury to evaluate motor function. Inflammation and oxidative damage within 24 hours of injury were evaluated by spectrophotometry. Immunofluorescence and neuroelectrophysiology were used to evaluate glial scar, neuronal protection, and nerve regeneration. The results showed that the Terzis grooming-test scores of the three groups that received treatment were better than those of the injury only group. Additionally, these three groups showed lower levels of C5-7 intramedullary peroxidase and malondialdehyde. Further, glial scar tissue in the C6 spinal segment was smaller and the number of motor neurons was greater. The endplate area of the biceps muscle was larger and the structure was clear. The latency of the compound potential of the myocutaneous nerve-biceps muscle was shorter. All these indexes were even greater in the melatonin + chondroitin sulfate ABC group than in the melatonin only or chondroitin sulfate ABC only groups. Thus, the results showed that melatonin combined with chondroitin sulfate ABC can promote nerve regeneration after nerve-root avulsion injury of the brachial plexus, which may be achieved by reducing oxidative damage and inflammatory reaction in the injury area and inhibiting glial scar formation.
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PMID:Melatonin combined with chondroitin sulfate ABC promotes nerve regeneration after root-avulsion brachial plexus injury. 3053 Oct 17


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