Biology subjects

Vivodtzev, I.

Publications and source records attributed to Vivodtzev, I..

3 recordsLinked to original sources

bioRxiv2026

A breathing-synchronized neuromuscular electrical stimulation algorithm for addressing respiratory impairments after cervical spinal cord injury

Cervical spinal cord injuries (cSCI) induce profound denervation in respiratory muscles leading to hypoventilation that compromises quality of life. Respiratory neuromuscular electrical stimulation of extra-diaphragmatic muscles (rNMES) could be a non-invasive approach to improve respiratory function following cSCI. However, asynchronous NMES with spontaneous respiration can feel unnatural or painful or even lead to potential complication, although synchronized stimulation may be more efficient to improve neuroplasticity after SCI. Here we developed a software-driven synchronized rNMES system aligned with spontaneous breathing, with preliminary validation in a mouse model of cSCI. MethodsAn Ordinary Differential Equation (ODE) was solved and fitted to experimental breathing signals obtained via respiratory function recording in mice which underwent cSCI. Optimal stimulation ODE-based parameters were then identified for both intercostal and abdominal muscle stimulation for breathing-synchronized rNMES training. Lastly, acute efficacy was assessed by evaluating the increase in chest position during intercostal stimulation, measured using a piezoelectric sensor on the thorax during stimulation. ResultsThe ODE-based breathing signals matched the experimental ones with an average coefficient of determination (R{superscript 2}) of 81%. The developed algorithm, Algostim, provided average theoretical optimal times of 0.10 {+/-} 0.01 s for intercostal and 0.17 {+/-} 0.02 s for abdominal muscles contraction. Synchronized intercostal stimulation led to twice greater change in chest amplitude compared to non-synchronized stimulation and there was a dose dependent effect with a minimal current intensity of 2 mA and an optimal stimulation reached with 3 mA. This innovative mathematical approach can optimize respiratory muscle stimulation while accounting for spontaneous breathing rate, establishing a framework for personalized rNMES therapies and enabling investigation into its underlying mechanisms.

physiology↗

bioRxiv2026

Cervical Repetitive Magnetic Stimulation Enhances Respiratory Recovery by Modulating Neuronal Plasticity After Cervical Spinal Cord Injury

Cervical spinal cord injury (SCI) frequently leads to life-threatening respiratory insufficiency by disrupting descending phrenic pathways. There is growing interest in non-invasive neuromodulatory approaches to enhance plasticity of spared respiratory circuits. We investigated whether cervical repetitive magnetic stimulation (rMS) applied to the injured cervical spinal cord promotes ventilatory recovery in a preclinical mouse model. Adult mice received a unilateral C3 hemicontusion followed by either rMS or sham stimulation. We found that rMS-treated mice significantly improved recovery of tidal volume and minute ventilation at 21 days post injury(dpi) compared to sham controls under various breathing conditions (isoflurane anesthesia, poikilocapnic phase and hypercapnic challenge). Correspondingly, diaphragm EMG enhanced ipsilateral hemidiaphragm activity in ventral and medial regions, and even contralateral hemidiaphragm activity in its ventral part. This was associated with a marked attenuation of the inflammatory response at the cervical spinal cord level. Indeed, rMS lowered astroglial, fibrotic scarring, pro-inflammatory CD68-, Iba1- microglial/macrophage markers. Moreover, perineuronal net expression (WFA positive staining) is globally reduced in the ventral spinal horn, whereas at the lesion site it is markedly increased and tightly wrapped around motoneurons. Together, these findings demonstrate that rMS promotes functional respiratory recovery after cervical SCI through combined enhancement of diaphragmatic motor output and modulation of the inflammatory and extracellular environment. Together, these functional and cellular findings indicate that spinal rMS promotes a permissive, pro-regenerative environment supporting respiratory circuit plasticity. We conclude that rMS significantly enhances ventilatory recovery via reduced inflammatory response and improved intraspinal rewiring after high cervical SCI, suggesting it is a promising non-invasive strategy. The ability of rMS to engage spared respiratory networks and support neuroplasticity highlights its promise as a safe, non-invasive therapeutic strategy with translational potential for rehabilitation of breathing function after SCI. One Sentence SummaryNoninvasive cervical magnetic stimulation improves breathing after spinal cord injury by boosting diaphragm activity and reducing inflammation.

neuroscience↗

bioRxiv2025

Unveiling Distinct Neuroimmune Responses in Mouse Models of Cervical Spinal Cord Injury: Hemisection versus Hemicontusion

Traumatic cervical spinal cord injury (cSCI) causes severe neurological deficits and long-term disability. Preclinical models such as cervical 2 (C2) hemisection (C2HS), resulting in disrupted communication between the respiratory centers and the phrenic motoneurons (PMN) pool, have been used since decades to study respiratory dysfunction and neuroinflammation after cSCI. Recently, contusive injuries such as C3 hemi-contusion (C3HC) have been increasingly used, as they induce phrenic motoneuron damage and offer a more clinically relevant model of SCI. However, these two different models may engage distinct pathophysiological cascades, raising concerns about the generalizability of findings across injury paradigms. In this study, we compared neuroimmune responses following C2HS or C3HC in mice. Animals underwent C2HS or C3HC, and spinal cord segments (C1-C8) were collected seven days post-injury for immuno-histological analyses around the lesion level and flow cytometry analyses at the lesion level. We observed that C2HS preserved more neurons and exhibited elevated CD86 and F4/80 expression. These markers are typically expressed by activated microglia and are indicative of a response oriented toward phagocytic and reparative functions. This phenotype was associated with limited pro-inflammatory cell infiltration and normalized level of systemic IL-6 in this model. Conversely, C3HC induced more extensive tissue damage, heightened microglial activation, a trend toward increased astrocytic reactivity, and significantly elevated CSPG levels on the contralateral side. Moreover, a persistent NK cell, neutrophil, and CD43 antigen-presenting cells infiltration, along with persistently high circulating IL-6 has been observed following C3HC. These findings demonstrate distinct neuroinflammatory signatures and repairing mechanisms between models, with C2HS promoting a microglia profile toward repair and C3HC leading to a prolonged and potentially harmful immune response. This study underscores, for the first time, how injury type shapes neuroimmune mechanisms, reinforcing the need for lesion-specific therapeutic strategies in cervical spinal cord injury. Highlight- C2 hemisection and C3 hemi-contusion trigger distinct neuroimmune responses in mice. - C2HS preserves ventral neurons and upregulates CD86 and F4/80, suggesting repair-oriented microglia. - C3HC induces CSPG accumulation, dendritic-like cell infiltration and prolonged systemic inflammation. - Injury model influences neuroimmune environment and regenerative potential after cervical SCI.

neuroscience↗