Effect of exogenous leukemia inhibitory factor on reparative regeneration of the peripheral nerve in mice

Abstract

The role of trophic and growth factors in the regeneration of the damaged peripheral nerve is known. The leukemia inhibitory factor (LIF) exhibits properties not only of the polyfunctional cytokine, but also the neurotrophic factor. Regeneration of the peripheral nerve is impaired during oxidative stress in the area of injury.The purpose of the work was to investigate the effect of recombinant human LIF (rhLIF) on the efficacy of reparative regeneration of the sciatic nerve.Materials and methods. Adult male FVB/N mice were divided into the following groups: sham-operated; trauma (neurotomy) of the right sciatic nerve; nerve injury and subcutaneous injection of rhLIF at a dose of 1 μg per animal daily from the third day after the nerve injury. The study was conducted 4 weeks after the injury. At morphometry, the density of nerve fibers in distal nerve segments after impregnation with nitric oxide silver was evaluated. The motor function was evaluated in the “open field” test by the number of crossed squares, and in footprint test by the distance between the extreme toes of the right foot. In the area of muscle injury, the content of malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase was estimated.Results. The total number of nerve fibers in the distal segment of the nerve of mice with trauma and injection of rhLIF is greater (p < 0.05) than in mice with only nerve injury and does not differ from sham-operated animals. Horizontal motor activity in mice with nerve injury is lower (p <0.05) than in sham-operated and cytokine injected mice. The distance between the extreme toes of the sham-operated mice is greater (p < 0.05) than in mice with nerve injury, as well as injuries and injections of rhLIF, but after the injection of cytokine, the rates are higher (p < 0.05) than in the group of mice without it. After the injury, the content of malondialdehyde and catalase activity increases in muscle tissue, while the activity of glutathione reductase decreases (p < 0.05). Under the influence of rhLIF, the parameters change to the values of sham-operated mice, and, in addition, the activity of the glutathione peroxidase is significantly increased.Conclusions. Injection of rhLIF to mice with a sciatic nerve injury promotes a more complete restoration of the structural organization of the damaged nerve and improves the motor function of the injured limb. At the same time, the balance between the factors of oxidative stress and antioxidant system is improved in the muscle tissue in the area of the nerve injury.

An Integrative Approach to the Current Treatment of HIV-Associated Neurocognitive Disorders and the Implementation of Leukemia Inhibitor Factor as a Mediator of Neurocognitive Preservation

“…It has been proven that the LIF takes part in mechanisms that promote the growth and regeneration of sensory neurons around the PNS after nerve damage [12]. A study performed with mice confirmed that the LIF promotes the reparative regeneration of peripheral nerves [13]. The study proved to be impactful due to it demonstrating that the LIF can act as both a polyfunctional cytokine and a neurotrophic factor.…”