Background. Peripheral nerve injuries are an extremely urgent problem today, especially in wartime. Very high percentage of disabled wounded people does not allow them to return to usual lives; up to 80 % of those injured are unfit for further service. Therefore, the restoration of peripheral nerves is not only a medical but also a social problem. The purpose was to study the functional restoration of the sciatic nerve after its traction injury and to determine the optimal treatment strategies. Materials and methods. The study was conducted on 30 outbred male rats with an average weight of 235 ± 55 g, which were kept in standard conditions of the vivarium of the State Institution “Romodanov Neurosurgery Institute of the National Academy of Medical Sciences of Ukraine” in compliance with all current bioethical standards. Rats were kept under a standard 12-hour light/dark cycle and provided with free access to food and water. The experiment was completed by sacrificing the animals with an intraperitoneal injection of a lethal dose of thiopental sodium. A traction injury to the sciatic nerve was simulated. Then the animals were divided into three groups depending on the chosen method of further treatment and observation. Assessment of restoration of the sciatic nerve function was performed using a comprehensive approach, which included Walking Track Analysis with determination of the sciatic functional index. Assessment was performed on the 30th and 60th day after surgery in groups I and II, as well as on the 30th and 60th day after traction injury in group III. Results. The worst recovery of the sciatic nerve function was observed in group II, while the best regeneration results were recorded in group III, where surgical intervention was not performed. At the same time, the indicators of groups I and III were statistically significantly different (p = 0.0027). High indicators in group III can be explained by the natural dynamics of nerve recovery after traction injury, which is confirmed by electron microscopic studies of damaged areas on the 15th, 30th and 60th day after injury. It should also be noted that the low coefficients of variation were obtained during the analysis of all data sets, which indicates high accuracy and reliability of the results. Conclusions. The study confirmed the effectiveness of natural regeneration of the sciatic nerve after traction injury, showing the best results in the non-surgical group. Surgical methods, such as epineural sutures and silicone tube insertion, provided partial recovery, but their effectiveness was limited.

Traction injuries of peripheral nerves are morphologically similar to combat-related trauma, where the kinetic energy of a wounding projectile causes nerve stretching and irreversible microscopic and ultrastructural changes, while the anatomical integrity remains preserved. The study of such changes is of critical importance in the context of regenerative technologies, especially under wartime conditions. Aim. To assess morphological changes in the structure of peripheral nerves at different time points during recovery after experimental traction injury of the sciatic nerve in rats. Materials and methods. A traction injury model of the sciatic nerve was modeled in 26 white outbred rats using a modified device. Animals were divided into two experimental groups based on the observation period: 15 days and 30 days after injury, and a control group of sham-operated rats (30 days). Morphometric analysis was performed to evaluate the impact of traction on the morphofunctional state of nerve fibers in the proximal and distal segments of the injured sciatic nerve. The density of stromal and parenchymal cells in both nerve segments was assessed. Results. On day 15, the stroma/parenchyma ratio in the proximal segment of the sciatic nerve was 0.17 (0.155; 0.188), showing a statistically significant two-fold increase compared to the control group. In the distal segment, the ratio was 0.229 (0.206; 0.257), also representing a two-fold increase. No statistically significant difference was observed between the distal and proximal segments at this time point. By day 30, the stroma/parenchyma ratio in the proximal segment was 0.124 (0.096; 0.148), with no statistically significant difference compared to the control group or the 15-day proximal group. In contrast, the distal segment showed a ratio of 0.228 (0.215; 0.261), which was 2.7 times higher than in the control group and 1.8 times higher than in the proximal segment at the same time point. On day 15, endoneural accumulation of myelin breakdown products was observed, indicating active degenerative changes in nerve fibers. By day 30, a reduction in the number and size of myelin droplets in the distal segment, along with restored waviness and increased compactness of endoneural fibers, indicated stabilization of tissue architecture. However, persistent edema remained in the proximal segment, though signs of perineurial activation and a glio-mesodermal response suggested adaptive processes and the beginning of nerve trunk remodeling. Сonclusion. Morphological analysis revealed distinct stages of change in the peripheral nerve following traction injury. On day 15, signs of Wallerian degeneration, edema, inflammatory responses, and activation of stromal cells and fibroblasts were evident. By day 30, inflammation had decreased and partial restoration of nerve fiber structure was observed, although degenerative changes and the risk of fibrosis persisted. Understanding the morphogenesis of these structural changes may help justify the optimal timing and extent of surgical intervention, including the use of regenerative therapies.

Abstract Introduction Military spinal cord injury is a severe injury, accompanied by high mortality and profound disability. Such injuries are usually penetrating, complex, infected, require intensive treatment at the initial stages and complex reconstructive neurosurgical interventions at later stages. This problem is especially relevant for Ukraine now, during the russian attack. Objectives The objective of the study was to investigate the short-term effect and safety of tissue engineering approach using umbilical cord arteries derived multipotent stem cells (UCA-MSCs) and heterogenous hydrogel for the consequences of military spinal cord injury neurosurgical treatment. Methods Patient B, the soldier of the National Guard of Ukraine, born on 1984, was wounded on 07/27/22 during a battle near Bakhmut. At 07/28/22 spinal cord decompression and fixation surgery was performed at the lower thoracic level (Th10). The patient had lower paraplegia (ASIA A), and neurogenic bladder. Complete anatomical and functional spinal cord transection below the Th10 level was confirmed. The patient was offered treatment in the frame of a research program "To investigate the effectiveness of regenerative cell technologies in the neurosurgical treatment of patients with demyelinating diseases of the CNS and cerebral palsy. № 0119U000112". UCA-MSCs for this case were isolated from a healthy human umbilical cord and had characteristics according to the minimal criteria of MSC. The hydrogel (poly[N-(2-hydroxypropyl)-methacrylamide]) is a commercial preparation synthesized in the laboratory of E. Pinet (FISO Technologies Inc., Quebec, Canada) by heterogeneous polymerization and association. 12/06/23 operation was performed: myeloradiculolysis, excision of areas of the glial scar of the spinal cord and filling of the defect with a heterogeneous hydrogel combined with UCA-MSCs. Results On the 6th months of observation, the patient has no infectious and inflammatory complications, and elements of deep sensitivity appeared in the proximal areas of the buttocks. No adverse effects during the observation period were recorded. Discussion More cases are needed to determine this method's safety and effectiveness, but early results are promising. A careful selection of patients is necessary for the use of this method, namely: confidence in the complete anatomical and functional transection of the spinal cord and the patient's informed consent for treatment.

Peripheral nerve injury is an extremely important medical and socio-economic problem. It is far from a solution, despite on rapid development of technologies. To study the effect of long-term electrical stimulation of peripheral nerves, we used a domestically produced electrical stimulation system, which is approved for clinical use. The study was performed on 28 rabbits. ?ontrol of regeneration was carried out after 3 month with morphologic techniques. The use of long-term electrostimulation technology leads to an improvement in the results of the recovery of the nerve trunk after an injury, both directly at the site of damage, when stimulation begins in the early period, and indirectly, after the nerve fibers reach the effector muscle.

To study many pathways in the pathogenesis of penetrating traumatic brain injury (TBI) and to improve treatment strategy for this type of injury, it is critical to develop an adequate experimental model. Depending on the purpose of the study of various aspects of the pathogenesis of TBI and brain response to trauma, a number of experimental models and their modifications were proposed: fluid-percussion brain injury, controlled cortical injury, inertial acceleration injury, mild traumatic brain injury. The above models of experimental brain injury cause focal or diffuse brain injury. The study of the possibility of dura matter (DM) regeneration and reduction of the adhesive process in the experiment with the use of biopolymers or their combinations will further recommend their effective use in clinical settings. Experimental model of penetrating TBI in rats, described in this chapter, is adequate to study the biological relationship between the DM, experimental biopolymers that can be used as substitutes for the DM, and the injured brain tissue.

Peripheral nerve injury is an extremely important problem during the war in Ukraine. In the overall pattern of injury, 5% of patients have peripheral nerve injuries and 1% have brachial plexus injuries. Under conditions of hostilities, this indicator increases to 70% or more. The victims are mainly young people of working age, which indicates the great medical and socio-economic significance of the problem. Materials and methods. The study was conducted on 28 rabbits Group 1 (n=7): suture of the sciatic nerve and implantation of the non-working antenna of the electrical stimulation device. Group 2 (n=7): sciatic nerve suture + implantation of an electric stimulator antenna in the same route as in group 1 and the beginning of stimulation on the 2nd day. Group 3 (n=7): sciatic nerve suture + implantation of an electric stimulator antenna in the same route as in group 1 and the beginning of stimulation 3 weeks after operation, when the first signs of regeneration occurred. Group 4 (n=7): autograft of the sciatic nerve + implantation of an electric stimulator antenna and the beginning of stimulation at a time point that will coincide with the beginning of signs of reinnervation of the effector muscle. Сontrol of regeneration was carried out in 12 weeks. The axial cylinder (AC) diameter, myelin thickness (MS) and MS/AC ratio were analyzed using electron mycroscopy. Results. It was showed a statistically significant increase of AC and MS indicators in the study group 2 relatively to comparison group 1, respectively, by 1.8 and 1.75 times. The increase of AC and MS in group 2, relatively to the comparison group and a visual decrease at the ultrastructural level of the number of destructively changed myelin sheaths (strengthening of reparative and regenerative processes) were detected. Conclusion. Therefore, long-term invasive electrostimulation of the damaged peripheral nerve has a positive effect on the regeneration of the neuromuscular complex.

Abstract Introduction Primary torsion dystonia (PTD) is a neurological disorder characterized by sustained or intermittent muscle contractions causing abnormal movements and/or postures with severe disability of young patients. Traditional therapies for PTD include oral anti-parkinsonism drugs, botulinum neurotoxin, pallidotomy and deep brain stimulation. Stem cell therapy is another promising treatment option, due to its neuroregenerative properties. Objectives The objective of the study was to investigate the effect of combined (intrathecal and intravenous) administration of umbilical cord derive stromal/stem cells (UC-MCS) on PTD reduction. Methods Patient M, born on 25.06.2004, fell ill gradually, 8 years ago developed signs of muscle dystonia, especially in right hand. Genetic tests were carried out, which revealed mutations in the DYT-1 gene. The diagnosis of primary torsion dystonia was established. Conservative treatment was not effective. The patient was offered treatment in the frame of research scientific program "To investigate the effectiveness of regenerative cell technologies in the neurosurgical treatment of patients with demyelinating diseases of the CNS and cerebral palsy. № 0119U000112" UC-MSCs for this study were isolated from healthy human umbilical cord and prepared due to the minimal criteria established by the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy. 3 injections of UC-MSC were performed with time interval of 6 month (intravenously and intrathecally in a dose of 6 × 107at each injection). Intrathecal administration was performed according to the typical method of performing lumbar puncture in compliance with the rules of asepsis and antiseptics in the operation room using local anesthesia. Results Prior to stem cells injection, the patient's Unified Dystonia Rating Scale (UDRS) dystonia movement score was 15, which progressively decreased after procedure to 13, 10, 7 and 4 after 6, 12, 18 and 24 months respectively. There was a significant improvement in the patient's quality of life. Discussion UC-MSC significantly reduce dystonia in patient. This result is probably achieved due to the neuroregenerative and neurotrophic effects of UC-MSCs. Study results suggest the need to provide larger multicenter randomized studies with more sophisticated methods of investigations.

Multiple sclerosis is a demyelinating disease of the nervous system that affects young people of working age and quickly leads to disability. Treatment of this pathology with umbilical cord mesenchymal stem cells is promising, given their immunomodulatory and neurotrophic properties. The study involved 27 patients diagnosed with multiple sclerosis, 12 of whom underwent combined treatment (intravenous and intrathecal administration) of umbilical cord multipotent mesenchymal stromal/stem cells. The effectiveness of treatment was determined by the degree of neurological deficit and spasticity. Combined treatment with umbilical cord mesenchymal stem cells significantly improves the condition of patients with multiple sclerosis and promotes the regression of neurological deficits and spasticity. This treatment is safe, but for a deeper study, it is necessary to continue research in this area.

Reinnervation of skeletal muscles, wich occurs in time, is considered a factor in preventing muscle atrophy and potentially successful functional recovery. Morphometry of denervated muscles makes it possible to assess the dynamics of muscle atrophy after various methods of repairing of a damaged peripheral nerve. The aim - evaluate histological changes and morphometry of m. gastrocnemius in rats after complete neurotomy and nerve repair techniques. In rats the sciatic nerve was crossed and sutured with 4 epineural sutures, 2 sutures with DuraSeal, and 2 sutures with Tisseel. On the 14th, 30th, and 60th day histological changes of m.gastrocnemius were examined and morphometry was performed based on two parameters: muscle fiber diameter and collagen density. Skeletal muscles morphometry was performed after sciatic nerve neurotomy and subsequent microsurgical repair. Muscle fiber wasting was already detected on the 14th day after epineural suture with DuraSeal, and in the Tisseel group - on the 30th day after sciatic nerve damage. The average diameter of muscle fibers in the DuraSeal group increased significantly by the day 60 due to the appearance of hypertrophied fibers. In areas of wasting, connective tissue density increased, which did not change quantitatively during the experiment, while the use of DuraSeal and Tisseel delayed the development of fibrosis for up to the 30th day. Application of DuraSeal and Tisseel with epineural suture delays the development of fibrosis and wasting in denervated muscles during the reinnervation period.

Demyelinating diseases, especially multiple sclerosis (MS) is not only medical but also socio-economic issue. Unsatisfactory quality of life and high degree of disability in these patients require the implementation of the advanced treatments, such as stem cell transplantation. Numerous experimental and clinical studies are being conducted, revealing new mechanisms of the action of stem cells in demyelinating diseases. Further research is needed to understand many more aspects of clinical use. This review is devoted to the use of regenerative cell technologies in the treatment of demyelinating diseases, the current state and prospects of the approach to the treatment of such pathology with stem cells.

Cerebral palsy remains a significant problem today, despite scientific and technological progress. The high degree of disability and unsatisfactory quality of life of patients in this category, necessitates the search for and implementation of the latest treatments, one of which is cell transplantation. The use of regenerative cell technologies in the treatment of patients with cerebral palsy is extremely promising. Numerous experimental studies have significantly expanded the understanding of the mechanisms of the effect of the use of stem cells in cerebral palsy. Clinical applications of stem cells of different origins are safe, which is one of the prerequisites for continuing research in this area. This review is devoted to the use of regenerative cell technologies in the treatment of cerebral palsy, the current state and prospects of the approach to the treatment of cerebral palsy with stem cells.

Mechanical damage to the peripheral nerve is a fairly common type of injury, which is characterized by a complex of long-term neurological disorders and require significant financial costs. The aim of this work is to evaluate the efficiency of sciatic nerve (SN) regeneration after neuroraphy using epineural suture (ES), polyethylene glycol hydrogel (PEG), and fibrin glue (FG). The studies were carried out on 30 white outbred male rats, which were divided into six experimental groups: Group №1: intact rats; Group №2: Sham operated; Group №3: complete transection of the SN; Group №4: nerve repair with ES; Group №5: nerve repair with PEG; Group №6: nerve repair with FG. Functional recovery was assessed at 1, 2, 3, 4 postoperative weeks using a walking-track analysis with subsequent determination of the sciatic nerve functional index (SFI). At 4 weeks, electroneuromyography, histological and morphometric analyzes were performed. The combined analysis indicated that PEG significantly improved functional recovery, both in the SFI index and in the skeletal muscle M-response. Compared to ES and PEG, the use of FG was reflected in a lower significance of the indicators compared to PEG. Statistical analysis indicates a positive effect of PEG and FG on nerve regeneration, although significantly greater remyelination (analysis based on fiber diameter) was confirmed only in the PEG group, which explains the faster functional recovery of the limb. PEG in the form of a hydrogel is a more promising agent in microsurgical restoration of damaged nerves as an adhesive, it promotes rapid nerve regeneration, denervated muscle re-innervation and functional limb recovery.

Background. Penetrating spinal cord injury with a foreign body in the spinal canal is one of the most common spinal cord injuries during wartime; the experimental reproduction of particular elements of complex interaction between a foreign body and the spinal cord is complicated.Objective. To examine clinical and pathomorphological features of the model of this type of spinal cord injury.Materials and methods. Animals: albino male rats (5.5 months, 300 grams, inbred line, the original strain is Wistar); experimental groups: basic (spinal cord injury + immediate homotopical implantation of a fragment of the microporous hydrogel – a foreign body [n=10]); comparison groups (spinal cord injury [n=16], spinal cord injury + immediate homotopical implantation of chemically identical macroporous hydrogel NeuroGel™ [n=20]). Model of injury: left-side spinal cord hemisection at ТXI level; monitoring the function of hind legs — the BBB scale; pathomorphological study: conventional histological techniques, transmission electronic microscopy.Results. Compression of the spinal cord by biologically compatible foreign body significantly worsens the course of the regeneration process; during the first 8 weeks the hind ipsilateral leg function indicator (HI LFI) in animals was the lowest one — (1.30±0.94) points by BBB scale; during the 3rd–4th month HI LFI increases to 2.35±0.95 points by BBB scale, which is likely due to the change in the form of a foreign body and its utilization, decrease of the pressure on the spinal cord. On the 24th week of the follow-up HI LFI was (8.45±0.92) points (in NeuroGelTM group) compared with (2.35±0.95) points by BBB scale (in the group with a foreign body). During the experiment a foreign body, unlike the fragments of the NeuroGelTM, was not integrated into the tissue of the spinal cord, was surrounded by a thick fibrous capsule, hardly infiltrated by tissue component. Morphological picture in the contra-lateral part of the spinal cord at the level of injury did not change.Conclusion. The model satisfactorily a mechanical component of a foreign body effect on the spinal cord tissue, presents the picture of post-traumatic syndrome of spasticity; reducing the spinal cord compression even at the late period of injury significantly improves the regeneration process.