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Motor disorders are among the most common consequences of severe craniocerebral injury (traumatic brain injury — TBI). Deeper insights into pathophysiological mechanisms of these disorders is important both from a theoretical point of view and in terms of improving neurorehabilitation approaches.The aim of the study was to investigate the correlation of right–sided posttraumatic hemiparesis severity with composite characteristics of fractional anisotropy (FA) in the segments of the corpus callosum (CC), corticospinal tract (CST) and the inferior fronto-occipital fasciculus (IFO) at different stages of traumatic disease (acute, subacute and long-term periods).Material and methods. Cases of 43 patients with TBI were analyzed (28 men and 15 women aged 13 to 59 years, mean age 28±9 years). Forty patients were diagnosed with severe TBI with diffuse axonal damage, three patients had moderate severity TBI. Long-term follow up included continuous clinical and neurological examination with evaluation of patient’s level of consciousness using the CRS-R scale, and the degree of motor deficits in right-sided hemiparesis using a five-point scale. During three post-TBI periods (up to 1 month, from 1 to 6 months, and from 6 to 12 months), patients were examined using diffusion tensor MRI (DTI), tractography and FA. Motor, cortico-spinal tracts and IFO were divided by measurement grid, correlations between FA and scores of right-sided hemiparesis were calculated for each segment.Results. FA correlations (P0.05) with the severity of hemiparesis were established not only for CST motor-specific segments, but also for some CC and IFO segments. In the early period of TBI significant correlations with hemiparesis severity were found not only in the contralateral CST segments, but also in the ipsilateral ones. Significant differences in FA in the related CC and CST segments were found between the groups with good and limited motor recovery: at all stages after TBI, FA was higher in patients with successful recovery.Conclusion. The results of the study provide better insight into pathophysiological mechanisms of post-traumatic motor disorders development, therefore favoring optimization of therapeutic strategies.

The aim of the study. To identify alterations of motor connectome in patients with varying degrees of hemi-paresis after severe traumatic brain injury (TBI) versus healthy volunteers.Material and methods. The study included 29 patients with TBI aged 18 to 35 years and 23 healthy volunteers aged 20 to 32 years. Participants underwent a comprehensive clinical and neuroimaging study. Motor impairment was evaluated via muscle strength assessment using a five-score scale. The fMRI data were processed using a dedicated CONN software package. Anatomical 3-D connection masks of the whole brain motor functional system in the predetermined regions of interest (ROIs) were used for the assessment. Then the group indicators of functional connectivity (statistical significance of the connection) were computed.Results. It was established that the structure of connections in healthy individuals performing active movement with the right (leading) hand is determined by formation of focus in the cortical and subcortical ROIs in the contralateral hemisphere. With passive movement of the right hand the pale ball becomes functionally active in addition to the activated areas. The striopallidar system structures became active on both sides, and connectivity with the additional motor cortex and the motor cortex of the ipsilateral hemisphere emerged as the paresis increased during active movement. The focus of motor activity during passive movement was determined in the motor cortex and putamen, which makes it possible to use a passive test in patients with gross motor disorders or unconsciousness for a full assessment of the entire structural and functional brain connectome.Conclusion. As hemiparesis increased in patients after severe traumatic brain injury, a decrease in the total number of connection appeared; simultaneous engagement of ancient primordial structures, such as bilateral activation of pale globes, demonstrated neuroplasticity.

In recent years, researchers have often encountered the significance of the aberrant metabolism of tumor cells in the pathogenesis of malignant neoplasms. This phenomenon, known as the Warburg effect, provides a number of advantages in the survival of neoplastic cells, and its application is considered a potential strategy in the search for antitumor agents. With the aim of developing a promising platform for designing antitumor therapeutics, we synthesized a library of conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones. To gain insight into the determinants of the biological activity of the prepared compounds, we showed that the conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones, which are cytotoxic agents, demonstrate selective activity toward a number of tumor cell lines with glycolysis-inhibiting ability. Moreover, the results of molecular and in silico screening allowed us to identify these compounds as potential inhibitors of the pyruvate kinase M2 oncoprotein, which is the rate-determining enzyme of glycolysis. Thus, the results of our work indicate that the synthesized conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones can be considered a promising platform for designing selective cytotoxic agents against the glycolysis process, which opens new possibilities for researchers involved in the search for antitumor therapeutics among compounds containing piperidone platforms.

Severe traumatic brain injury (TBI) accompanied by impaired consciousness manifesting as prolonged postcoma unawareness (PCU) is one of the current medical and social problems causing high morbidity and mortality worldwide. Difficult recovery of such patients necessitates the development of additional neurorehabilitation approaches, including neuromodulation methods, as well as the search for objective markers of treatment efficacy. Aim of the study: to evaluate the effect of therapeutic rhythmic transcranial magnetic stimulation (rTMS) on fMRI resting state networks (RSN) in PCU after severe TBI. Materials and Methods. We analyzed individual fMRI RSN in three patients with PCU before and after a course of rTMS performed at different timepoints after severe TBI and with different efficacy of treatment. We assessed the topography and quantitative characteristics of the networks (DMN, sensorimotor, control functions, left and right fronto-parietal, auditory, and speech) known to be most significant for recovery of consciousness. Results. We found a trend toward normalization of RSN topography as well as an increase in the integral index of network intensity in two of three patients with a distinct increase in consciousness after a course of rTMS. Conclusion. Using case observations, we have demonstrated the therapeutic efficacy of rTMS and feasibility of using fMRI RSN as a reliable diagnostic approach in PCU following severe TBI.