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We studied the neuroprotective effect of local application of methylprednisolone in combination with a block copolymer after contusion spinal cord injury in rats. Histological analysis of the spinal cord showed that delivery of a complex of methylprednisolone with a block copolymer reduced the volume of white and gray matter lesions. An increase in the amplitude of the evoked response of the gastrocnemius muscle was observed during epidural stimulation of the spinal cord 6 h after the injury. The maximum amplitude of the muscle response was greater in the group with local delivery of the methylprednisolone complex with the polymer 72 h after the injury. The obtained results demonstrate the neuroprotective effect of the local administration of the complex and allow to make positive prognosis for the recovery of the sensorimotor functions in rats., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

Monomelic amyotrophy, also known as Hirayama disease, is a rare neurological disorder characterized by focal and latent onset of upper limb weakness and atrophy in the absence of sensory deficits, bulbar or pyramidal signs. It usually occurs in young patients. The disease usually begins unnoticeably and progresses slowly, and can manifest itself as unilateral or asymmetrical weakness, as well as atrophy of the distal upper limb. Sensory disturbances, reflex changes and signs of lesions of lower motor neurons are rare. This article describes a case of a patient with complaints of weakness not only in the upper but also in the lower extremities.

Background and purpose - The frequency of primary anterior cruciate ligament (ACL) reconstruction is increasing resulting in more ACL revision surgeries. Therefore, we assessed survival rates of 2 different grafts for ACL revision surgery at 1- and 5-year follow-ups, as well as physical activity levels of patients after revision surgery.Patients and methods - This is a retrospective cohort study involving 218 patients (176 males) who had revision surgery for anterior cruciate ligament injuries between 2008 and 2017 at the Clinic of Traumatology, Orthopedics and Joint Pathology Clinic (I.M. Sechenov First Moscow State Medical University). A comparison group involved 189 patients with only primary surgery. Surgical interventions were performed according to the standard procedure using bone-patellar tendon-bone (BTB) and semitendinosus/gracilis (ST/G) autografts. The results of revision surgery were assessed at 1- and 5-year follow-ups by using the Lysholm and International Knee Documentation Committee scores.Results - Malpositioned bone tunnels were found in 87/218 patients (40%). At 1 and 5 years postoperatively, the revision BTB group had significantly better results in terms of IKDC and Lysholm scores than the revision ST/G group (p = 0.03, Mann-Whitney U-test), and these results were comparable to those in the comparison group. Graft survival after revision was lower than after the primary operation. However, the survival rate of 80% is quite high and is consistent with previous findings. There were no statistically reliable differences in survival between ST/G and BTB autografts.Interpretation - The graft choice for revision ACL surgery should be decided upon before surgery based on, among other things, the state of bone tunnels, in particular their position and degree of bone resorption. Tunnel widening that exceeds 14 mm (osteolysis) would require 2-stage surgery using a BTB autograft with bone plugs because it is larger than the ST/G autograft.

Localized carrier-mediated administration of drugs is a promising approach to treatment of acute phase of spinal cord injury (SCI) as it allows enhanced and/or sustained drug delivery to damaged tissues along with minimization of systemic side effects. We studied the effect of locally applied self-assembling micellar formulation of methylprednisolone succinate (MPS) with trifunctional block copolymer of ethylene oxide and propylene oxide (TBC) on functional recovery and tissue drug content after SCI in rats in comparison with local and systemic administration of MPS alone. Variations in the amplitude of motor evoked responses in the hindlimb muscles induced by epidural stimulation during acute phase of SCI and restoration of movements during chronic period after local vs. systemic application of MPS were evaluated in this study. Results demonstrate that local delivery of MPS in combination with TBC facilitates spinal cord sensorimotor circuitry, increasing the excitability. In addition, this formulation was found to be more effective in improvement of locomotion after SCI compared to systemic administration. LC-MS/MS data shows that the use of TBC carrier increases the glucocorticoid content in treated spinal cord by more than four times over other modes of treatment. The results of this study demonstrate that the local treatment of acute SCI with MPS in the form of mixed micelles with TBC can provide improved therapeutic outcome by promoting drug accumulation and functional restoration of the spinal cord.

Biofouling is among the key factors slowing down healing of acute and chronic wounds. Here we report both anti-biofilm and wound-healing properties of the chitosan-immobilized Ficin. The proposed chitosan-adsorption approach allowed preserving ~90% of the initial total activity of the enzyme (when using azocasein as a substrate) with stabilization factor of 4.9, and ~70% of its specific enzymatic activity. In vitro, the chitosan-immobilized Ficin degraded staphylococcal biofilms, this way increasing the efficacy of antimicrobials against biofilm-embedded bacteria. In vivo, in the presence of Ficin (either soluble or immobilized), the S.aureus-infected skin wound areas in rats reduced twofold after 4 instead of 6 days treatment. Moreover, topical application of the immobilized enzyme resulted in a 3-log reduction of S. aureus cell count on the wound surfaces in 6 days, compared to more than 10 days required to achieve the same effect in control. Additional advantages include smoother reepithelisation, and new tissue formation exhibiting collagen structure characteristics closely reminiscent of those observed in the native tissue. Taken together, our data suggest that both soluble and immobilized Ficin appear beneficial for the treatment of biofilm-associated infections, as well as speeding up wound healing and microbial decontamination., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Perineuronal nets (PNN) ensheath GABAergic and glutamatergic synapses on neuronal cell surface in the central nervous system (CNS), have neuroprotective effect in animal models of Alzheimer disease and regulate synaptic plasticity during development and regeneration. Crucial insights were obtained recently concerning molecular composition and physiological importance of PNN but the microstructure of the network remains largely unstudied. Here we used histochemistry, fluorescent microscopy and quantitative image analysis to study the PNN structure in adult mouse and rat neurons from layers IV and VI of the somatosensory cortex. Vast majority of meshes have quadrangle, pentagon or hexagon shape with mean mesh area of 1.29µm(2) in mouse and 1.44µm(2) in rat neurons. We demonstrate two distinct patterns of chondroitin sulfate distribution within a single mesh - with uniform (nonpolar) and node-enriched (polar) distribution of the Wisteria floribunda agglutinin-positive signal. Vertices of the node-enriched pattern match better with local maxima of chondroitin sulfate density as compared to the uniform pattern. PNN is organized into clusters of meshes with distinct morphologies on the neuronal cell surface. Our findings suggest the role for the PNN microstructure in the synaptic transduction and plasticity., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Electromyography methods were employed to examine the mechanisms underlying changes in the functional state of the contralateral neuromotor apparatus of rat gastrocnemius muscle during unilateral limitation of the hind leg motor function. Elimination of one hind leg from the total pattern of motor activity affected the state of contralateral neuromotor apparatus via changing the properties of motoneurons in the corresponding spinal motor center resulting mostly from activation of the bilaterally acting spinal mechanism.

In this study we investigated a motor-neuronal functional state based on H- and M-responses from m. quadratus plantae in dogs before and after experimental spinal cord contusion with and without following local intraoperative hypothermia. H- and M-responses from m. quadratus plantae were recorded during stimulation of the tibial nerve and results were compared between the groups. Our results demonstrate that local hypothermia applied after spinal cord contusion reduces amplitude of both M- and H-responses and also H(max)/M(max) ratio that may indicate depression of motorneurons excitability. After spinal cord contusion without following hypothermia the excitability of the spinal motorneurons during post-traumatic period, in opposite, was significantly increased. These results support a conclusion that intraoperative hypothermia after spinal cord contusion can delay development of functional excitability of the motoneurons and protect from further changes in H- and M-responses.

The goal of this work was to study the influence of daily 3-hr vibrostimulation of the supporting zones of the foot and 3-hr of usual locomotion on the functional state of the soleus, gastrocnemius, and tibial anterior muscles in rats after 7 and 14 days of hindlimb unloading. After 7 days of unloading the soleus weight decreased, while the weight of gastrocnemius and tibial anterior remained unchanged. After 14 days of hindlimb unloading a weight reduction was observed in all studied muscles. Vibrostimulation of the foot and supporting afferentation prevented the loss of weight in gastrocnemius and tibial anterior during the first week of unloading and reduced the negative effect of hindlimb unloading in 14 days. Our results demonstrate that the amplitude of the M-response after 7 days of hindlimb unloading was decreased predominantly in soleus as compared to gastrocnemius and tibial anterior. By the 14 day we observed restoration of the amplitude of the M-response in gastrocnemius and tibial anterior, and the increased amplitude of the M-response in soleus. Different techniques for foot stimulation in rats during hindlimb unloading demonstrated the positive effect in regard to M-response restoration--the amplitude of the M-response was increased in all studied muscles. Thus, our results demonstrate that foot vibrostimulation or supporting afferentation can completely prevent atrophy caused by hindlimb unloading in gastrocnemius and tibial anterior and decrease atrophy in soleus in rats.

Spontaneous cord dorsum potentials (spontaneous CDPs) are produced by the activation of dorsal horn neurons distributed along the L4 to S1 spinal cord segments, in Rexed's laminae III-VI, in the same region in which there are interneurons rhythmically bursting during fictive scratching in cats. An interesting observation is that spontaneous CDPs are not rhythmically superimposed on the sinusoidal CDPs generated during fictive scratching episodes, thus suggesting that the interneurons producing both types of CDPs belong to different spinal circuits. In order to provide experimental data to support this hypothesis, we recorded unitary activity of neurons in the L6 spinal cord segment. We found that the neurons firing rhythmically during the sinusoidal CDPs associated with the extensor, flexor or intermediate phases of scratching were not synchronized with the spontaneous CDPs. Moreover, we found that the neurons firing during the spontaneous CDPs were not synchronized with the sinusoidal CDPs. These results suggest that the neurons involved in the occurrence of spontaneous CDPs are not part of the spinal cord central pattern generators (CPGs). This study will be relevant for understanding the relationships between the spinal cord neuronal populations firing spontaneously and the CPGs, in the intact and injured spinal cord., (Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.)

Effects of unilateral damage of the rat sciatic nerve on the spinal motor centre of contralateral gastrocnemius muscle were investigated. The state of contralateral gastrocnemius muscle centre was assessed using the method of paired monosynaptic testings and posttetanic potentiation of reflex response on days 1, 5 and 10 after nerve damage. The obtained data indicate changes in reflex activity of contralateral motor centre in these conditions. The activation of contralateral reflex systems after nerve damage seems to provide regenerative reorganisation of the motor control in the conditions of traumatic influence.

Effects of daily 3-hr vibrostimulation of foot support zone and 3 hrs. of usual locomotion on titin N2A-isoform and proteolytic T2-fragment were studied in m. soleus of rats during 7-d suspension. Besides, effects of single one-hour support loading following 7-d weight-deprivation on titin N2A- and T2-forms were also evaluated in the muscle. Relative N2A content in m. soleus of the suspended group was noted to reduce approximately 25% as compared with the group of control. In the meantime, relative T2 content grew 2-3 times. Along with other changes in the muscle apparatus, N2A reduction contributes to the decline of m. soleus contractility in suspended rats, and development of the "hypogravity muscular syndrome" The daily 3-hr vibrostimulation of the foot support zones substantially (almost twice) decreased N2A disintegration with parallel reduction in approximately 1.5 times relative T2 content comparing with the Suspension group. Three hours of locomotion a day during suspension did not appear to decrease the relative N2A content in m. soleus. However, in this group of animals the relative T2 content in m. soleus was twice as high as in the control. Single-time presentation of support load for one hour soon after 7-d suspension resulted in more significant (approximately 30%) reduction in relative N2A content and twofold fall of relative T2 content as compared with m. soleus of the rats in group Suspension. These data attest to the leading role of support stimulation in maintaining the structural and functional properties of the musculoskeletal system, specifically the titin N2A-isoform content in m. soleus of rat deprived of gravitational loading. Besides, it was also shown that tracking changes in titin makes possible to follow the course of hypogravitational muscle syndrome and to evaluate effectiveness of preventive methods.

The effects of unilateral transection of the Achilles tendon (tenotomy) on the electromyographic characteristics of the gastrocnemius muscle on the contralateral side were studied in rats. Motor responses, reflex responses, and motor unit spike activity in the contralateral gastrocnemius muscle were studied in baseline conditions and on afferent stimulation before and 10 days after tenotomy. Changes in the nature of motor unit spike activity and responses to afferent stimulation were observed. The results obtained here demonstrate increases in the excitability of individual motoneurons in the contralateral motor center of the gastrocnemius muscle after exclusion of the symmetrical gastrocnemius muscle from the overall pattern of movement activity.

Electromyographic recordings of contralateral m. gastrocnemius of the rat after unilateral section of Achilles' tendon (tenotomy) were studied. Motor reflex, Hoffman reflex and firing of motor units of contralateral m. gastrocnemius were recorded in control and in 10 days after tendotomy. Motor units changed their firing in the background and in reaction to sciatic nerve stimulation. The results of study showed that unilateral section of Achilles' tendon increased the excitability of single motoneurons of contralateral spinal senters.