THE EFFECTS OF HYDROCORTISONE ON SYNAPTIC PROCESSES IN PARKINSON'S DISEASE UNDERLYING THE POTENTIAL THERAPEUTIC STRATEGIES.

The study was carried out electrophysiological effects of hydrocortisone for protection on the prelimbic cortex (PrL) neurons in rats, particularly in response to high-frequency stimulation (HFS) of the Caudate-Putamen nuclear complex (CPu) on the models of Parkinson's disease (PD). The study involved 19 rats of the Albino line, each weighing 250 gr. The rats were divided into three experimental groups: intact, rotenone model of Parkinson's disease (PD), and rats with PD but treated with hydrocortisone for protection. Extracellular recording was conducted to measure the impulse activity of single neurons in the prelimbic cortex (PrL) particularly in response to high-frequency stimulation (HFS) of the Caudate-Putamen nuclear complex (CPu) on the models of PD and PD treated with hydrocortisone for protection. In rats with the PD model, there was a decrease in post-stimulus synaptic depressor tetanic effects compared to the norm. This means that the ability of synapses to depress their activity after stimulation was reduced in PD. Conversely, excitatory effects increased in PD rats compared to the norm. This indicates an increase in the excitatory response of neurons in the PD model. When hydrocortisone was applied in PD rats, the frequency of impulse activity dropped sharply, even falling below the levels observed in the normal condition. This indicates that hydrocortisone treatment mitigated the heightened neural activity induced by PD, possibly returning it to a more normal state. Overall, these findings suggest that PD alters synaptic responses and neural activity in the PrL, and hydrocortisone treatment seems to reverse some of these effects.

MORPHOLOGICAL AND BEHAVIORAL ANALYSIS OF THE PROTECTIVE EFFECTS OF BACTERIAL MELANIN IN A RAT MODEL OF PARKINSON'S DISEASE.

A comparative study of the morphological and functional state of the microvasculature of the substantia nigra pars compacta of the brain (SNc) and bone marrow of rats was carried out using the rotenone model of Parkinson's disease (PD) and with subsequent administration of bacterial melanin (BM). The detection of microvasculature was carried out according to the histoangiological method of Chilingaryan. Animal behavior was studied using a cylinder test. An analysis of morphometric data showed that, in comparison with control animals, experimental animals with rotenone dysfunction showed an increase in capillary diameters and a general reduction in the capillary link in SNc. Behavioral tests have shown that the animals with rotenone intoxication exhibit a form of behavior inherent in PD (freezing, immobility, apathy). Under the influence of BM, the diameter of the capillaries in the SNc approaches the norm, and the capillary link is restored. Due to the protective effect of BM in rats with rotenone intoxication, the trophism of the brain tissue increases as a result of the approach of the lumen of the vessels to the norm and the opening of new branches in the capillary network, an increase in the density of capillaries, which ensures the safety of nerve cells. Animal behavior indicators are close to normal. A comprehensive analysis of cytogenetic data of rat bone marrow was also carried out. In animals with PD, compared to controls, there is a significant increase in the amount of polyploid cells (PC) and a decrease in the level of mitotic index (MI), which usually manifests itself in inflammatory processes and is accompanied by inhibition of bone marrow hematopoiesis. Under the influence of BM, a tendency towards normalization of MI was noted and a significant decrease in the percentage of PC was obtained, which possibly indicates its beneficial effect. The data obtained suggest that BM can be used as a therapeutic agent in the treatment of PD.

ASSESSMENT OF RAT BRAIN MORPHOFUNCTIONAL STATE IN A PARKINSON'S MODEL: INFLUENCE OF THERAPEUTIC AGENTS OF ANIMAL AND SYNTHETIC ORIGINS.

In neurodegenerative diseases, particularly in Parkinson's disease (PD), antinociceptive centers are often implicated in neurodegeneration, leading to persistent pain unresponsive to narcotic substances. This study investigated the periaqueductal gray matter (PAG) and the nucleus raphe magnus (NRM), components of the brain's antinociceptive system. In conditions of rotenone intoxication (an experimental PD model), morphological changes in intracellular structures were observed in PAG and NRM neurons, indicating metabolic disorders characteristic of PD (alterations in the shape and size of neuronal bodies and processes, disruption of acid phosphatase activity in neuron cytoplasm). Under the influence of bacterial melanin and in combination with synoestrol, positive changes in structural properties were observed in PAG and NRM neurons compared to the rotenone model of PD. This included the preservation of the morphological characteristics typical of these brain regions, with cells exhibiting shapes and sizes close to normal. Furthermore, under the influence of these therapeutic agents, an increase in phosphatase activity in cell cytoplasm was detected, indicating an acceleration of metabolic processes (metabolic activation) disrupted by rotenone intoxication. The data obtained suggests that bacterial melanin and synoestrol may act as potential neuroprotective agents against PAG and NRM neurons in the rat brain in the rotenone model of PD. Further research is needed to elucidate the mechanisms of action of therapeutic doses and propose their use in the treatment of PD, either in isolation or combination therapy.

The protective effect of vipera raddei venom on peripheral nerve damage.

Acute experiments were performed on spinal rats to study the protective actions of Vipera raddei venom after section of the sciatic nerve. Individual spike activity was recorded from interneurons and motoneurons in the lumbar segment of the spinal cord, induced by stimulation of the sciatic nerve and the extensor (gastrocnemius) and flexor (peroneus communis) nerves on the lesioned and symmetrical intact sides in controls and after daily injections of venom for four weeks. In animals not treated with Vipera raddei venom, the lesioned side lacked interneuron and motoneuron responses to stimulation of the extensor and flexor nerves of the distal stump, though these were present on stimulation of the contralateral side; responses were the inverse of this on the intact side, due to the failure of the proximal and distal stumps to fuse, as also demonstrated by atrophy of the distal stump of the sciatic nerve and the absence of movement activity in the lesioned limb. Treatment with Vipera raddei venom led to restoration, by four weeks, of interneuron and motoneuron responses on the lesioned side on stimulation of the ipsilateral nerves and on the intact side by stimulation of the contralateral nerves; this is the result of apparent fusion of the proximal and distal stumps of the lesioned nerve. Further evidence for this was hypertrophy of the distal stump and restoration of movement activity in the lesioned limb. These results show that Vipera raddei venom has potential for use in regenerating damaged peripheral nerves.

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.

Plastic changes in the intact cerebral cortex as a result of local injury to a symmetrical division of it.

The representation of the radial nerve in a symmetrical division of the opposite cerebral hemisphere was studied using an evoked potentials technique at various periods (from 1.5 months to 1 year 8 months) following the electrolytic destruction of the associative parietal cortex in chronic experimental conditions in cats. An expansion of the zone of the representation of the radial nerve was identified, starting from three to four months following the operative intervention. The activity of lactate dehydrogenase and malate dehydrogenase, as well as the spectrum of lactate dehydrogenase isoenzymes in the indicated time periods. The possible factors underlying the changes observed are discussed.