[THE EFFECTS OF THE STIMULATION OF HYPOTHALAMIC NUCLEI ON THE INFERIOR VESTIBULAR NUCLEUS AFTER LONG-TERM VIBRATION ACTION AND ADMINISTRATION OF PROLINE RICH PEPTIDE-1].

Vestibular dysfunctions after vibration action in a considerable degree by adaptive-adjustment changes of neurotransmitter processes are determined and regulation of which is possible by endogenous factors, particularly hypothalamic proline rich peptide-1. On Albino rats synaptic changes in single neurons of the inferior vestibular nucleus during high-frequency stimulation of hypothalamic supraoptic and paraventricular nuclei in condition of vibration action and systemic use of proline rich peptide-1 were studied. The poststimulus spike activity of inferior vestibular nucleus neurons in norm was manifested mainly in the form of tetanic potentiation and posttetanic potentation after vibration action. The combination of vibration action and proline rich peptide-1 restores the true balance of excitatory and inhibitory poststimulus reactions and increased level of survival the inferior vestibular nucleus neurons.

Protective effect of a new hypothalamic peptide against cobra venom and trauma-induced neuronal injury.

A study of separate and combined actions of cobra venom (CV) and a new hypothalamic proline-rich polypeptide (PRP) isolated from magnocellular cells (NPV and NSO) on intoxication- and trauma-induced neuronal injury (during 3-4 weeks after hemisection with and without PRP treatment) was carried out. The registration of background and evoked impulse activity flow, changes in spinal cord (SC) inter- and motoneurons, responding to flexor, extensor, and mixed nerve stimulation in both acute and chronic experimental neurodegeneration was performed. The facilitating effect of PRP on the abovementioned neurons was revealed. High doses of CV that evoked the neurodegenerative changes demonstrated an inhibitory effect. In this case PRP treatment both before and after intoxication restored electrical neuronal activity to baseline level and higher. These results are evidence of protective action of PRP. The low doses of CV induced a facilitating effect. The combination of CV and PRP displayed an additive facilitating effect; in a number of cases the repeated administration of CV led to decrease of significant PRP effect till baseline level (for example, the inhibition after primary response prior to secondary late discharge). Greater liability of the secondary early and late long-time discharges of poststimulus responses, differently expressed in various neuron types of SC to chemical influences is of interest. PRP-induced inhibition of the paroxysmal activity related with CV action is also very interesting. Morpho-functional experiments with SC injury demonstrated the abolition of difference in the background and evoked SC neuronal activity below the section and on intact symmetric side after daily PRP administration for 3 weeks. PRP hindered the scar formation and activated neuroglia proliferation; it promoted white matter element growth, hampered the degeneration of cellular elements, and protected against tissue stress. Our results favor the combined use of PRP and CV in clinical practice for the treatment of neurodegeneration of toxic and traumatic origin, as well as specific neurodegenerative diseases such as Alzheimer's.

Immunohistochemical study of immunophilin 1-15 fragment in intact frog brain, and in the brain and spinal cord of intact and spinal cord hemisectioned rats.

Previously by immunohistochemical technique the distribution of immunophilin 1-15 fragment (IphF) isolated from bovine hypothalamus was examined in various tissues (heart, lung), including immune system organs (spleen and thymus) of intact rats. IphF-like immunoreactivity (IphF-LI) was revealed in several cell types: lymphocytes, monocytes, macrophages and mast cells. In the present study the immunohistochemical localization of IphF was examined in intact rat and frog brains. In rat brain several cell groups concentrated particularly in the supraoptic nucleus (SON) of hypothalamus, medulla oblongata (reticular formation, olives, hypoglossal and facial motor nuclei) and cerebellum (lateral cerebellar nucleus) demonstrated IphF-LI. In frog hypothalamus (SON) the same working dilution (1:5000) of IphF-antiserum revealed very strong immunoreactivity. In the paraventricular nucleus (PVN) IphF-LI varicosities were scattered around the immunonegative cells. The second cell groups showing IphF-LI in the frog brain were gliocytes (mainly the astrocytes). Besides, IphF distribution was investigated in rats subjected to hemisection of spinal cord (SC) with and without administration of proline-rich polypeptide (PRP). PRP was isolated from bovine neurohypophysis neurosecretory granules, produced by magnocellular nuclei of hypothalamus. Hemisection of SC led to changes of IphF distribution in the hypothalamus. In PRP treated animals IphF showed no immunoreactivity. PRP is suggested to act as a neurotransmitter and neuroregulator.

Protection against snake venom-induced neuronal injury by the new hypothalamic neurohormone.

The action of PRP is characterized by the pronounced activation of the background activity (BA) of the brain spinal cord, and the degree of the activity depends on BA initial level. The typical peculiarity of Vipera raddei venom influence is the initial increase in frequency of BA with subsequent depression. A preliminary injection of PRP has a protective effect at subsequent influence of venom. In animals with hemisection the PRP increases the decreased activity of neurons on injury side. Taking into consideration the protective peculiarities of PRP in the relationship to snake venom and the possibility of the latter to stabilize and prolong the action of drugs (in the case of PRP) combined with them, it is supposed that the mentioned use of the combination in clinical practice will be perspective. The data obtained testify the PRP to be a neuroprotector against many toxic compounds formed in organism (glutamate, ceramid, beta-amyloid neurotoxisity, etc.). Investigations in this aspect are still in the process.

Comparison of the protection against neuronal injury by hypothalamic peptides and by dexamethasone.

The comparative study has been carried out on hypothalamic neurohormone (proline-rich polypeptides-PRP) and synthetic glucocorticoid dexamethasone (DEX) protective properties at the systemic (i/m) administration. Both background and evoked electrical activity (on n.ischiadicus stimulation) of single neurons in the lumbo-sacral part (laminae II-VI and VII-VIII by Rexed) and field potentials (FP) of spinal cord were recorded during acute experiments on intact spinal rats, subjected to Vipera Raddei (VR) venom intoxication, and chronic spinal cord trauma (hemisection). The action of PRP was characterized by the pronounced activation of the background activity (BA) with adaptive effect, depending on dose and initial level of BA, by results of the statistical analysis. A high effect is received from comparatively small doses. For comparison it was used strong glucocorticoid DEX, possessing single-directed but less expressed excitative action on investigated spinal cord neurons. The initial increase of BA frequency with subsequent depression was the typical symptom of venom influence. A protective effect of preliminary PRP injection is revealed on the succeeding VR venom influence. Use of PRP and DEX causes the increase of reduced activity of neurons on the injury side of animals with spinal cord hemisection. It provides the possibility of the therapeutic utilization. It was revealed considerably more expressed PRP action on neurodegenerative process connected to spinal cord injury (in comparison with DEX). The influence of hormones was compared in identical conditions of experiments on non-injured (control) and injured sides. Taking into consideration revealed protection characteristic of PRP and also the ability of snake venom to stabilize and to prolong its action combined with these preparations, the assumption is made on prospective use of the specified combination in clinical practice.

Synaptic responses of red nucleus neurons in the alert cat to cortical and cerebellar inputs.

Postsynaptic potentials of neurons of the red nucleus (RN), evoked to stimulation of the sensorimotor region of the cerebral cortex and cerebellar nucleus interpositus, were studied in chronic experiments on alert cats by means of an intracellular recording technique. Movements of the animals were restricted by rigid fixation (through a special device previously attached to the head) of the animal's head on the frame of the stereotaxic apparatus. Rubrospinal neurons were identified according to their antidromic activation in response to stimulation of the rubrospinal tract at the decussation level. A decrease in the critical level of depolarization necessary for spike generation was shown to be a characteristic peculiarity for mono- and polysynaptic reaction of the RN neurons in the alert animals. A rare possibility of recording separate EPSPs, the presence of burst discharges of rubrospinal neurons as well as a higher activity of RN interneurons was observed.

Distribution and peculiarities of axon collateral branching of rubro-spinal neurones in brainstem structures.

Peculiarities of axon branching and distribution of rubro-spinal neurones in various brainstem structures were studied in acute cats using the technique of intracellular recording of antidromic action potentials as well as collision testing. Axon collaterals of rubro-spinal neurones into the main sensory trigeminal nucleus, facial nerve nucleus, descending (inferior) vestibular nucleus, lateral reticular nucleus, external cuneate nucleus, gracile and main cuneate nuclei were identified. Correlation between the antidromic impulse conduction time along the stem axon before and after collateral branching and the time of impulse conduction in the collaterals themselves was analysed. The number of axon collaterals of individual rubro-spinal neurones to particular brainstem structures was studied. A tendency was observed for the synchronous arrival of rubro-spinal impulses to various brainstem centres, due to an increase in conductance velocity the further away these centres were from the red nucleus.