Studies of the protective effect of the hypothalamic peptide PRP-3 on spinal cord neurons at different periods after lateral hemisection

Abstract

The protective effect of a new neurosecretory cytokine, proline-rich peptide (PRP-3) that is produced by the cells of the hypothalamic paraventricular and supraoptical nuclei was studied after lateral hemisection of the spinal cord. Experiments were performed at different postoperative periods (3, 4, and 5 weeks) under conditions of daily administration of PRP-3 in order to study dynamics of the development of rehabilitation states. Flow of single impulse activity induced by stimulation of the mixed (N. ischiadicus), extensor (N. peroneus communis), and flexor (N. gastrocnemius) nerves, at the level of the transection site and lower than it, on the damaged and symmetrical intact sides of the spinal cord was observed in comparison with the control in the interneurons and motoneurons of the spinal cord after daily administration of PRP-3 for 3–4 weeks. PRP-3 was shown to restore activity of the neurons of the lumbar part of the spinal cord and to cause more pronounced early and late postimpulse manifestations of the activity of spinal cord neurons. Morphological studies demonstrated that PRP-3 exhibited a powerful effect on the migration of motoneurons to the transection site and on intensification of proliferation of glial elements. Moreover, PRP-3 stimulated the migration of motoneurons to more distant regions along with penetration to the white matter at the level of the symmetrical undamaged side of the spinal cord. Glial and neurite penetration into places without symphysis, predominantly in the grey matter of the spinal cord, and the prevention of scar formation in the regions of damage were demonstrated. PRP-3 facilitated active ingrowth of vessels in the damaged regions. This process, in turn, favors regeneration with the restoration of locomotor activity at the rehabilitation stage. PRP-3 prevented scar formation and favored ingrowth of nerve fibers of the white matter in the damaged area and thus prevented degeneration of neuroglial elements. This fact was confirmed by recording activity at the level of the injury and by restoration of locomotor activity on the damaged side. This properties of PRP-3 may allow its use in clinical practice for the prevention of neurodegeneration induced by craniocerebral and spinal trauma.