ИСТИНА

Induction of nerve regeneration after trauma is an important therapeutic goal. The most promising approach is to stimulate nerve regeneration with the help of neurotrophic proteins, e.g., brain-derived neurotrophic factor (BDNF). In our study, we have tested the ability of pVax-based plasmid which contains the optimized cDNA of human BDNF to enhance nerve regeneration in mice. It's possible because BDNF sequence in humans and mice share 98.8% homology. During surgery the common peroneal nerve was crushed and the solution of pVax-hBDNF plasmid was transcutaneously injected into the tibialis anterior muscle (this muscle is innervated by nerve endings of the common peroneal nerve). In vitro tests confirmed stable and potent secretion of hBDNF by muscle explants for at least 7 days after transfection. As for nerve regeneration we found that gene transfer of hBDNF to denervated muscle enhances recuperation of nerve morphology and function compared to control vector (pVax). Our findings were confirmed by histological studies which showed increased number of NF200-positive structures in nerves from animals of hBDNF gene transfer group and by electrophysiological studies which revealed faster conductivity and larger amplitude of the compound nerve action potentials. The most likely mechanism of action of BDNF-encocding plasmid is mediated by stimulation of neurons survival, nerve endings growth and proliferation of Schwann cells by elevated BDNF production. Thus, our data indicate that the transfer of genes encoding neurotrophic factors can be used to enhance regeneration of injured nerves after appropriate safety tests.