- MeSH
- chybná zdravotní péče etika prevence a kontrola psychologie MeSH
- endokrinní systém enzymologie fyziologie MeSH
- lékařská onkologie * metody trendy MeSH
- lidé MeSH
- neurochirurgie * metody organizace a řízení trendy MeSH
- neurodegenerativní nemoci diagnóza etiologie chirurgie MeSH
- neurologie * metody organizace a řízení trendy MeSH
- poranění míchy diagnóza chirurgie prevence a kontrola MeSH
- psychochirurgie etika metody trendy MeSH
- regenerace nervu fyziologie genetika imunologie MeSH
- transplantace etika metody trendy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- rozhovory MeSH
The growth-associated protein 43 (GAP-43) is known as a marker of regenerating nerve fibers and their continuous remodeling in the adult human skin. The purpose of this pilot study was to investigate a possible role for GAP-43 in the detection of the early stages of small-fiber neuropathy in patients with type 2 diabetes mellitus (DM2) as compared with a well- established and validated parameter - intra-epidermal nerve fiber density (IENFD) of protein gene product 9.5 (PGP 9.5) immunoreactive intra-epidermal C fibers. In a group of 21 patients with DM2 within three years of diagnosis (13 men, 8 women; mean age 53.9±12.8; range 30-74) and a group of 17 healthy volunteers (8 men, 9 women; mean age 55.8±8.5; range 45-70 years), skin punch biopsies were taken from a distal calf and double immunostained with both PGP 9.5 and GAP-43. In healthy controls, 96.8% of 629 PGP 9.5 immunoreactive fibers were immunostained with GAP-43; the proportion of PGP 9.5 intra-epidermal nerve fibers immunoreactive for GAP-43 in control subjects ranged from 86.5 to 100%. In DM2 patients, IENFD was significantly lower compared to controls (median, 1.5 vs. 11.2/mm; p<0.001). The proportion of GAP-43 immunoreactive intraepidermal nerve fibers was significantly lower in DM2 patients compared to healthy controls (73.6% of 337 PGP 9.5 positive fibers; p<0.001); ranged from 0 to 98.1%. In conclusion, these results show that impaired regeneration of intra-epidermal C fibers in the early stages of type 2 diabetes mellitus, as indicated by GAP-43, might be a marker of incipient diabetic neuropathy.
- MeSH
- diabetes mellitus 2. typu genetika metabolismus patofyziologie MeSH
- diabetické neuropatie genetika metabolismus patofyziologie MeSH
- dospělí MeSH
- kůže inervace metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- nervová vlákna nemyelinizovaná patologie fyziologie MeSH
- nervová vlákna fyziologie MeSH
- pilotní projekty MeSH
- protein GAP-43 biosyntéza genetika MeSH
- regenerace nervu genetika MeSH
- regulace genové exprese MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
BACKGROUND: Vascular endothelial growth factor (VEGF) is not only a potent angiogenic factor but it also promotes axonal outgrowth and proliferation of Schwann cells. The aim of the present study was to quantitatively assess reinnervation of musculocutaneous nerve (MCN) stumps using motor and primary sensory neurons after plasmid phVEGF transfection and end-to-end (ETE) or end-to-side (ETS) neurorrhaphy. The distal stump of rat transected MCN, was transfected with plasmid phVEGF, plasmid alone or treated with vehiculum and reinnervated following ETE or ETS neurorrhaphy for 2 months. The number of motor and dorsal root ganglia neurons reinnervating the MCN stump was estimated following their retrograde labeling with Fluoro-Ruby and Fluoro-Emerald. Reinnervation of the MCN stumps was assessed based on density, diameter and myelin sheath thickness of regenerated axons, grooming test and the wet weight index of the biceps brachii muscles. RESULTS: Immunohistochemical detection under the same conditions revealed increased VEGF in the Schwann cells of the MCN stumps transfected with the plasmid phVEGF, as opposed to control stumps transfected with only the plasmid or treated with vehiculum. The MCN stumps transfected with the plasmid phVEGF were reinnervated by moderately higher numbers of motor and sensory neurons after ETE neurorrhaphy compared with control stumps. However, morphometric quality of myelinated axons, grooming test and the wet weight index were significantly better in the MCN plasmid phVEGF transfected stumps. The ETS neurorrhaphy of the MCN plasmid phVEGF transfected stumps in comparison with control stumps resulted in significant elevation of motor and sensory neurons that reinnervated the MCN. Especially noteworthy was the increased numbers of neurons that sent out collateral sprouts into the MCN stumps. Similarly to ETE neurorrhaphy, phVEGF transfection resulted in significantly higher morphometric quality of myelinated axons, behavioral test and the wet weight index of the biceps brachii muscles. CONCLUSION: Our results showed that plasmid phVEGF transfection of MCN stumps could induce an increase in VEGF protein in Schwann cells, which resulted in higher quality axon reinnervation after both ETE and ETS neurorrhaphy. This was also associated with a better wet weight biceps brachii muscle index and functional tests than in control rats.
- MeSH
- dextrany diagnostické užití MeSH
- fluoresceiny diagnostické užití MeSH
- genetická terapie metody MeSH
- krysa rodu rattus MeSH
- mícha patologie MeSH
- modely nemocí na zvířatech MeSH
- nemoci periferního nervového systému patologie terapie MeSH
- nervová vlákna myelinizovaná patologie MeSH
- nervus musculocutaneus metabolismus patologie fyziologie MeSH
- neurologické vyšetření MeSH
- neurony metabolismus patologie MeSH
- potkani Wistar MeSH
- přední končetina patofyziologie MeSH
- regenerace nervu genetika fyziologie MeSH
- rhodaminy diagnostické užití MeSH
- vaskulární endoteliální růstový faktor A biosyntéza metabolismus terapeutické užití MeSH
- velikost orgánu fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH