Immunomodulatory and neurotropic activities of synthetic peptides in a model of brain injury in rats

Treatment of consequences of traumatic brain injury (TBI) remains one of the current problems of medicine. To increase the effectiveness of treatment of post-traumatic complications, various drugs are recommended, including the peptide with neuromodulatory activity Semax.

The present study aims to determine the presence of neuro- and immunoprotective properties of the synthetic peptide PR5, composed of fragments of proline-rich antimicrobial peptides.

The work was performed on male Wistar rats weighing 300-350 g. The “falling weight” model of mechanical brain injury was used, which mainly causes diffuse brain damage. The synthesized peptide PR5, composed of fragments of known proline-rich peptides of animal neutrophils, and the peptide preparation Semax in the form of a 1% aqueous solution were used. The drugs were administered intranasally 1 hour after TBI, then twice a day for 4 days at a dose of 100 mg/kg body weight. Control animals received physiological saline in the same regimen as the peptide preparations.

TBI led to a significant decrease in body weight, but in rats receiving the peptide preparation Semax, the decrease in body weight was significantly less than in control animals, and the PR5 preparation completely prevented the decrease in body weight after TBI. After TBI, the proliferative activity of lymphocytes was suppressed and the cytotoxicity of NK cells decreased. In animals treated with peptide preparations, there was no significant suppression of NK cell cytotoxicity, and the proliferative activity of lymphocytes was restored to the level of control animals by day 14 after TBI. Both peptide preparations used contributed to higher locomotor activity, and in animals treated with the PR5 peptide, this type of activity reached the parameters of control animals. The reduction in freezing duration in groups treated with peptide preparations indicates the presence of a sedative effect.

The peptide preparation PR5 was active in this series of experiments, showing immunotropic and neuroprotective activity comparable to the Semax preparation. Further studies aimed at confirming the identified types of activity of the peptide preparation PR5 may justify its prospects for clinical use as a new nootropic agent.

1. Ametov A., Shustov S., Khalimov Yu. Endocrinology. A textbook for medical students. Мoscow: GEOTARMedia, 2016. 352 p.

2. Ashmarin I.P., Yeshchenko N.D., Karazeeva E.P. Neurochemistry in tables and diagrams. Мoscow: Exam, 2007. 144 p.

3. Bureš J., Burešová O., Huston J.P. Techniques and basic experiments for the study of brain and behavior. Amsterdam; New York: Elsevier Science Publishers B.V., 2nd ed., 1983. 326 p.

4. Muraeva N.A. Influence of chronic stress on body weight and immune organs of experimental animals of early age. Volgograd Journal of Medical Scientific Research, 2019, no. 4, pp. 3-7. (In Russ.)

5. Shamova O.V., Lesnikova M.P., Kokryakov VN., Shkhinek E.K., Korneva E.A. Effect of defensins on the blood level of corticosterone and the immune response during stress. Bull. Exp. Biol. Med., 1993, Vol. 115, pp. 728-731.

6. Shanin S.N., Fomicheva E.E., Filatenkova T.A., Serebryanaya N.B. Correction of disorders of neuroimmune interactions in experimental traumatic brain injury with recombinant interleukin-2. Medical Immunology (Russia), 2018. Vol. 20, no. 2, рp. 171-178. doi:10.15789/1563-0625-2018-2-171-178.

7. Zhu Q., Hu K., Mulay S. Isolation and structure of corticostatin peptides from rabbit fetal and adult lung. Proc. Natl Acad. Sci. USA, 1988, Vol. 85, pp. 592-596.