Non-viral transfer of BDNF and uPA stimulates peripheral nerve regeneration.
Peripheral nerves connect brain and spinal cord with the extremities and inner organs, and nerves injury can lead the disability and social exclusion. Growth factors and other natural stimulators of regeneration processes look very promising as future medicines. In our study, we tested the influence of genetic constructions that contain genes of brain-derived neurotrophic factor and urokinase plasminogen activator on nerve's structure and function after traumatic and ischemic injuries. Injection of pVax1-hBDNF and pVax1-muPA after traumatic injury led to better restoration of nerve's structure and function compared to similar parameters of control group mice. In ischemic injury model pVax1-hBDNF and pVax1-muPA slowed and reduced the damage progression and stimulated nerve regeneration as well. However, the treatment with pVax1-muPA was less effective after the traumatic injury. As we chose a non-viral method of gene delivery during our study the optimal conditions of plasmid intramuscular delivery were also determined.
Institute of Experimental Cardiology, Russian Cardiology Research and Production Complex, 3rd Cherepkovskaya Street 15a, Moscow 121552, Russia(1).
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Karagyaur
Department of Biological and Medical Chemistry, Faculty of Fundamental Medicine, Lomonosov Moscow State University, Lomonosovsky prospekt, 31/5, Moscow 119192, Russia(2).
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Dyikanov
Institute of Experimental Cardiology, Russian Cardiology Research and Production Complex, 3rd Cherepkovskaya Street 15a, Moscow 121552, Russia(1).
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Makarevich
Institute of Experimental Cardiology, Russian Cardiology Research and Production Complex, 3rd Cherepkovskaya Street 15a, Moscow 121552, Russia(1).
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Semina
Institute of Experimental Cardiology, Russian Cardiology Research and Production Complex, 3rd Cherepkovskaya Street 15a, Moscow 121552, Russia(1).
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Stambolsky
Institute of Experimental Cardiology, Russian Cardiology Research and Production Complex, 3rd Cherepkovskaya Street 15a, Moscow 121552, Russia(1).
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Plekhanova
Department of Biological and Medical Chemistry, Faculty of Fundamental Medicine, Lomonosov Moscow State University, Lomonosovsky prospekt, 31/5, Moscow 119192, Russia(2). Electronic address: n_i_kalinina@mail.ru.
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Kalinina
Institute of Experimental Cardiology, Russian Cardiology Research and Production Complex, 3rd Cherepkovskaya Street 15a, Moscow 121552, Russia(1); Department of Biological and Medical Chemistry, Faculty of Fundamental Medicine, Lomonosov Moscow State University, Lomonosovsky prospekt, 31/5, Moscow 119192, Russia(2).
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Tkachuk
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007511:Ischemia / Q000150:complications; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009416:Nerve Regeneration / Q000235:genetics*; D059348:Peripheral Nerve Injuries / Q000628:therapy; D010957:Plasmids / Q000008:administration & dosage; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
D019208:Brain-Derived Neurotrophic Factor; D014568:Urokinase-Type Plasminogen Activator
BDNF; Nerve regeneration; Urokinase