DYNAMICS OF NEUROLOGICAL DEFICITS IN RATS WITH THE SIMULATED EQUIVALENT OF MULTIPLE SCLEROSIS UNDER THE INFLUENCE OF CRYOEXTRACTS OF THE PLACENTA AND SPLEEN, AS WELL AS THE CONDITIONED MEDIUM OF MESENCHYMAL STEM CELLS

Abstract

Background. Neurodegeneration in multiple sclerosis (MS) is caused by the attack of autoreactive lymphocytes on the myelin sheath and the endogenous failure of remyelination, which ultimately leads to the accumulation of neurological disability. The chronic course of MS can lead to significant mental and physical symptoms and irreversible neurological disorders, including muscle weakness, ataxia, tremors, spasticity, paralysis, balance disorders, cognitive impairment, vision loss, diplopia, dizziness, swallowing and speech disorders, sensory deficits, bladder and bowel dysfunction, pain, fatigue, and depression. Existing immunomodulatory drugs, despite the fact that they are very effective in reducing the frequency of MS relapses, do not prevent progressive neurodegenerative processes and do not have a regenerative effect, but can cause significant side effects. Objective: to characterize the expressiveness of the neurological deficit according to the indicators of muscle tone and behavioral reactions in the model of multiple sclerosis – in allergic encephalomyelitis (AEM) in rats against the background of the use of cryoextracts of the placenta (СEP) and spleen (СES), and conditioned medium of mesenchymal stem cells (MSC-CM). Methods. Experimental studies were conducted on 42 non-linear laboratory male rats weighing 200–220 g. AEM was modeled by injecting encephalitogenic emulsion subcutaneously into the base of the tail at the dose of 1.0 ml/kg of body weight. The emulsion consisted of Freund's complete adjuvant and allogeneic brain homogenate in a 1:1 ratio. AEM treatment was carried out from the 12th to the 20th day of the experiment. CEP, CES and MSC-CM were administered every other day (a total of 5 injections), on days 12, 14, 16, 18 and 20, respectively. The study of neurological deficits in the model of AEM in rats was carried out by evaluating the muscle tone and behavioral reactions of animals (namely, emotional activity) in dynamics, according to the simulation of AEM ("0" day), on the 12th and 21st days of the experiment. Results. A statistically significant (p=0.009) decrease in muscle tone by 73.8% and a statistically significant (p=0.02) decrease in emotional activity by 70.4% relative to baseline values were noted in rats with simulated AEM on the 12th day of the experiment. It was found that on the 21st day of the experiment, against the background of the introduction of CES, the muscle strength of rats with AEM decreased statistically significantly (р˂0.03) by 53.3%, and against the background of the use of CES, the similar indicator decreased (р˂0.01) by 61.3% relative to the indicators in the corresponding groups on the 12th day of the experiment, which was 1.8 and 2.1, respectively, inferior to the effectiveness of the reference drug methylprednisolone. The study showed that the introduction of MSC-CM led to an almost complete stop of the loss of muscle strength in rats with AEM, since the indicated indicator on the 21st day of the experiment was practically comparable to the similar indicator on the 12th day of the experiment and was 4.7±0.5 s, respectively and 4.6±0.4 s, which by 26.9% (р=0.16) exceeded the effectiveness of both the studied cryoextracts and the reference drug methylprednisolone in terms of their ability to slow down the loss of muscle mass. Conclusions. According to the expressiveness of preservation of muscle tone in rats with AEM on day 21 relative to the indicator on day 14, it is advisable to place the investigated cell-free cryopreserved biological agents in the following sequence: MSC-CM (+3.1%; p=0.37) ˃ CEP (-53 .3%; p˂0.03) ˃ CES (-61.3%; p˂0.01). According to the magnitude of the increase in emotional activity in rats with AEM on the 21st day of the experiment relative to the indicators on the 14th day, it is advisable to place the investigated cell-free cryopreserved biological agents in the following sequence: MSC-CM (+288.9%; p˂0.01) ˃ CEP (+162 .5%; p=0.09) ˃ CES (+150.0%; p=0.09).