V článku je uveden přehled poznatků o úloze nervového růstového faktoru (NGF – nerve growth factor) v mechanismech nocicepce a jeho biochemických a fyziologických vazeb na periferní a centrální úrovni. Z těchto patofyziologických poznatků vyplynula syntéza tanezumabu jako vysoce selektivní IgGZ A monoklonální protilátky selektivně vázající nervový růstový faktor, kterou je možné použít k léčení bolestivých stavů při jeho zvýšení.
In this article is described the survey of the findings of the role of nerve growth factor (NGF)in the mechanism of nicieption and it ́s biochemical and physiological processes on the peripheral and central level. These pathophysiological findings serve as a background for the construction of tanezumab as a hight selective IgGZA and monoclonal antidote chemicaly binding NGF nerve growth factor, wich is the possible the use for treatment especially of the chronic pain, caused by its increasing. of NGF.
- MeSH
- Pain * drug therapy MeSH
- Chronic Pain drug therapy MeSH
- Antibodies, Monoclonal, Humanized therapeutic use MeSH
- Humans MeSH
- Neoplasms physiopathology MeSH
- Nerve Growth Factor * antagonists & inhibitors physiology adverse effects MeSH
- Pain, Intractable drug therapy MeSH
- Peripheral Nervous System physiology drug effects MeSH
- Nerve Regeneration MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Progress in brain research ; Vol. 103
XVI, 413 s. : bar.fot., obr., tab., grafy ; 25 cm
- Keywords
- VEGF, růstový faktor, angiogeneze, neuroproliferace,
- MeSH
- Biological Therapy trends MeSH
- Financing, Organized MeSH
- Angiogenesis Inducing Agents MeSH
- Humans MeSH
- Nervous System Physiological Phenomena physiology MeSH
- Nerve Regeneration physiology MeSH
- Vascular Endothelial Growth Factors physiology therapeutic use MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Review MeSH
1st ed. 273 s., obr.
... Vol. 1: Neural repair and plasticity -- Vol. 2: Medical neurorehabilitation ... ... of neural plasticity -- 1 Anatomical and biochemical plasticity of neurons: regenerative growth of axons ... ... Cohen -- Section B: Neural repair -- Section ? ... ... Wong nerve regeneration 487 32 Biomimetic design of neural prostheses 587 -- Wesley J. ... ... Wood 513 34 Status of neural repair clinical trials in brain diseases 615 -- Olle F. ...
1st ed. 2 sv. : il., tab. ; 26 cm
- MeSH
- Neuronal Plasticity MeSH
- Trauma, Nervous System rehabilitation MeSH
- Nerve Regeneration MeSH
- Rehabilitation MeSH
- Publication type
- Monograph MeSH
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- neurologie
- traumatologie
- neurochirurgie
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
- Dextrans diagnostic use MeSH
- Fluoresceins diagnostic use MeSH
- Genetic Therapy methods MeSH
- Rats MeSH
- Spinal Cord pathology MeSH
- Disease Models, Animal MeSH
- Peripheral Nervous System Diseases pathology therapy MeSH
- Nerve Fibers, Myelinated pathology MeSH
- Musculocutaneous Nerve metabolism pathology physiology MeSH
- Neurologic Examination MeSH
- Neurons metabolism pathology MeSH
- Rats, Wistar MeSH
- Forelimb physiopathology MeSH
- Nerve Regeneration genetics physiology MeSH
- Rhodamines diagnostic use MeSH
- Vascular Endothelial Growth Factor A biosynthesis metabolism therapeutic use MeSH
- Organ Size physiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
This study elucidated the stage-specific roles of FGF2 signaling during neural development using in-vitro human embryonic stem cell-based developmental modeling. We found that the dysregulation of FGF2 signaling prior to the onset of neural induction resulted in the malformation of neural rosettes (a neural tube-like structure), despite cells having undergone neural induction. The aberrant neural rosette formation may be attributed to the misplacement of ZO-1, which is a polarized tight junction protein and shown co-localized with FGF2/FGFR1 in the apical region of neural rosettes, subsequently led to abnormal neurogenesis. Moreover, the FGF2 signaling inhibition at the stage of neural rosettes caused a reduction in cell proliferation, an increase in numbers of cells with cell-cycle exit, and premature neurogenesis. These effects may be mediated by NUMB, to which expression was observed enriched in the apical region of neural rosettes after FGF2 signaling inhibition coinciding with the disappearance of PAX6+/Ki67+ neural stem cells and the emergence of MAP2+ neurons. Moreover, our results suggested that the hESC-based developmental system reserved a similar neural stem cell niche in vivo.
- MeSH
- Cell Differentiation drug effects MeSH
- Cell Line MeSH
- Time-Lapse Imaging MeSH
- Chromones pharmacology MeSH
- Fibroblast Growth Factor 2 pharmacology MeSH
- Immunohistochemistry MeSH
- Humans MeSH
- Human Embryonic Stem Cells cytology metabolism MeSH
- RNA, Small Interfering metabolism MeSH
- Membrane Proteins metabolism MeSH
- Morpholines pharmacology MeSH
- Neural Stem Cells cytology metabolism MeSH
- Neurogenesis drug effects MeSH
- Neurons cytology metabolism MeSH
- Zonula Occludens-1 Protein antagonists & inhibitors genetics metabolism MeSH
- Microtubule-Associated Proteins metabolism MeSH
- Nerve Tissue Proteins metabolism MeSH
- Pyrimidines pharmacology MeSH
- Receptor, Fibroblast Growth Factor, Type 1 metabolism MeSH
- RNA Interference MeSH
- Signal Transduction drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
