Survival of trauma-injured neurons in rat brain by treatment with proline-rich peptide (PRP-1): an immunohistochemical study.

The objective of this immunohistochemical research was to reveal the distribution of a proline-rich peptide-1 (PRP-1) in various brain structures of intact and trauma-injured rats and to identify the mechanisms of promotion of neuronal recovery processes following PRP-1 treatment. PRP-1, produced by bovine hypothalamic magnocellular cells and consisting of 15 amino acid residues, is a fragment of neurophysin vasopressin associated glycoprotein isolated from bovine neurohypophysis neurosecretory granules. PRP-1-immunoreactivity (PRP-1-IR) was detected in the brain of intact rats in the neurons of paraventricular (PVN) and supraoptic (SON) nuclei in the hypothalamus, in almost all cell groups in the medulla oblongata, in Purkinje and some cerebellar nuclei cells, and in nerve fibers. At 3 weeks after hemisection of the spinal cord (SC) an asymmetry of PRP-1 localization in the PVN and SON was observed: no PRP-1-IR was exhibited at the affected sides of both nuclei. Daily intramuscular administration of PRP-1 for 3 weeks significantly increased the number of PRP-1-immunoreactive (PRP-1-Ir) varicose nerve fibers, and cells in PVN and SON and in cell groups of the limbic system and brain stem. Tanycytes in the median eminence and covering ependyma also demonstrated strong PRP-1-IR. PRP-1 treatment also activated neuropeptide Y-IR (NPY-IR) in nerve fibers and immunophilin fragment-IR (IphF-IR) in lymphocytes and nerve cells. A strong increase of PRP-1-IR was observed in the PVN and SON of SC-injured rats following the treatment with another PRP (PRP-3). Preliminary physiological data demonstrate that PRP-3 is more "aggressive" in the recovery processes than PRP-1. Based on the findings regarding PRP action on neurons survival, axons regeneration, and the number of IphF-Ir lymphocytes and NPY-Ir nerve fibers, PRP is suggested to act as a neuroprotector, functioning as a putative neurotransmitter and immunomodulator.