Neuroprotective Action of Hypothalamic Peptide PRP-1 at Various Time Survivals Following Spinal Cord Hemisection

Abstract

The purpose of the present study was to evaluate the neuroprotective action of proline-rich peptide-1 (PRP-1) produced by hypothalamic nuclei cells (nuclei paraventricularis and supraopticus) following lateral hemisection of spinal cord (SC). The dynamics of rehabilitative shifts were investigated at various periods of postoperative survival (1-2, 3, and 4 weeks), both with administration of PRP-1 and without it (control). We registered evoked spike flow activity in both interneurons and motoneurons of the same segment of transected and symmetric intact sides of SC and below it on the stimulation of mixed (n. ischiadicus), flexor (n. gastrocnemius) and extensor (n. peroneus communis) nerves. In the control group (administration of 0.9% saline as placebo), no significant decrease of post-stimulus activity of neurons was observed on the transected side by the 2nd week. This activity strongly decreased by week 3 postaxotomy, with some increase on the intact side, possibly of compensatory origin. No shifts occurred by the 4th week. Regardless of the period of administration, PRP-1 increased neuronal activity on the transected side, with the same activation levels on both SC sides. These data were confirmed by histochemical investigation. PRP-1 administration, both daily and every other day, for a period of 2-3 weeks led to prevention of scar formation and promotion of the re-growth of white matter nerve fibers in the damaged area. It also resulted in prevention of neuroglial elements degeneration and reduction in gliosis expression in the lesion supporting neuronal survival. Thus, PRP-1 achieved protection against "tissue stress", which was also confirmed by the registration of activity on the level of transection and restoration of the motor activity on the injured side. The obtained data propose the possibility of PRP-1 application in clinical practice for prevention of neurodegeneration of traumatic origin.

Cytostatic Effect of the Hypothalamic Cytokine PRP-1 is Mediated by mTOR and cMyc Inhibition in High Grade Chondrosarcoma

“…This cytokine is also a mediator of the hypothalamus-neurohypophysis-bone marrow axis and a powerful immunomodulator [1,2]. Strong antibacterial (in vivo) and antiviral (in vitro) properties of hypothalamic proline rich peptides [3], anti neurodegenerative effects [4] and immunotropic properties [5] provide evidence for the existence of brain protective mechanisms against infection, neurodegeneration, immunodefficiencies [6] and tumors [7,8,[11][12][13]. We demonstrated that PRP-1 induced decay of tumor cells L929 and decreased mitotic activity of transformed mouse fibroblast cells, dose response growth inhibition of Jurkat cells, and inhibition of lymphosarcoma in vivo [1,7,8].…”

Antitumorigenic Effect of Brain Proline Rich Polypeptide-1 in Human Chondrosarcoma

“…This cytokine is also a mediator of hypothalamus-neurohypophysis-bone marrow axis as well as a powerful immunomodulator [1,2]. Strong antibacterial (in vivo) and antiviral (in vitro) properties of hypothalamic proline rich peptides [3] as well as antineurodegenerative [4] and their immunotropic properties [5] provide evidence for the existence of brain protective mechanisms against infection, neurodegeneration, immunodeficiencies [6] and tumor. We demonstrated that PRP-1 induced decay of tumor cells L929 and decreased mitotic activity of those transformed mouse fibroblast cells [1,[7][8][9][10].…”

Myc-oncogene Inactivating Effect by Proline Rich Polypeptide (PRP-1) in Chondrosarcoma JJ012 Cells

“…The phenomenon of interleukin secretion by hypothalamic magnocellular nuclei as well as biosynthesis of a new class cytokines (PRPs) illustrate the capability of the brain neuroendocrine cells synthesize cytokines along with vasopressin, oxytocin and organotropic (cardioactive) neurohormones. Strong antibacterial (in vivo) and antiviral (in vitro) properties of hypothalamic proline rich peptides [3] as well as antineurodegenerative [4] and their immunotropic properties [5,6] provide evidence for the existence of brain protective mechanisms against infection, neurodegeneration, immunodeficiencies [6] and tumor [7][8][9][10].…”