{"id":684,"date":"2019-11-24T17:54:24","date_gmt":"2019-11-24T17:54:24","guid":{"rendered":"http:\/\/stimup.org\/?page_id=684"},"modified":"2025-07-12T03:07:15","modified_gmt":"2025-07-12T03:07:15","slug":"recent-manuscripts","status":"publish","type":"page","link":"https:\/\/stimup.org\/?page_id=684","title":{"rendered":"LIB\u042fARY"},"content":{"rendered":"\n

Our Recent Manuscripts<\/a><\/strong><\/h2>\n\n\n\n
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New manuscript “Case report: Combined transcutaneous spinal cord stimulation and physical therapy on recovery of neurological function after spinal cord infarction”<\/p>\n\n\n\n

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To evaluate the effect of transcutaneous (tSCS) and epidural electric.\u00a0The case of a 37-year-old woman who suffered from spinal cord infarction (SI), resulting in a complete spinal cord injury (AIS A, neurological level T10), and autonomic dysfunction is presented. This study aimed to assess the effect of transcutaneous Spinal Cord Electrical Stimulation (tSCS) on improving motor, sensory, and autonomic function after SI. During the first 8 months, tSCS was applied alone, then, physical therapy (PT) was included in the sessions (tSCS+PT), until completion of 20 months. Compared to baseline, at 20 months, an increase in ISNCSCI motor (50 vs. 57) and sensory scores (light touch, 72 vs. 82; pinprick, 71 vs. 92) were observed. Neurogenic Bladder Symptoms Score (NBSS) changed from 27 at baseline to 17 at 20 months. ISAFSCI scores in sacral autonomic function improved from 0 pts (absent function) to 1 pt. (altered function) indicating better sphincter control. As this is the first report on the use of tSCS in the case of SI, future studies in a case series are warranted.<\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n

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Our new manuscript “Selective Activation of the Spinal Cord with Epidural Electrical Stimulation”.<\/p>\n\n\n\n

In this study, we exploited different ESS paradigms, designed as either Spatial-Selective Stimulation (SSES) or Orientation-Selective Epidural Stimulation (OSES), and compared them to Conventional Monopolar Epidural Stimulation (CMES). SSES, OSES, and CMES. The results demonstrate that the amplitudes of SEMPs in hindlimb muscles depend on the orientation of the electrical field and vary between stimulation modalities. These findings show that the electric field applied with SSES or OSES provides more selective control of amplitudes of the SEMPs as compared to CMES. Spinal cord epidural stimulation applied with SSES or OSES paradigms in the rodent model could be tailored to the functional spinal cord neuroanatomy.<\/p>\n<\/div>\n\n\n\n

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New manuscript “Consecutive Transcutaneous and Epidural Spinal Cord Neuromodulation to Modify Clinical Complete Paralysis\u2014the Proof of Concept”. <\/p>\n\n\n\n

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To evaluate the effect of transcutaneous (tSCS) and epidural electrical\u00a0spinal cord stimulation<\/a>\u00a0(EES) in facilitating volitional movements, balance, and nonmotor functions, in this observational study, tSCS and EES were consecutively tested in 2 participants with motor complete\u00a0spinal cord injury<\/a> Two participants (a 48-year-old woman and a 28-year-old man), both classified as motor complete spinal injury, were enrolled in the study. Both participants went through a unified protocol, such as an initial electrophysiological assessment of neural connectivity, consecutive tSCS and EES combined with 8 wks of motor training with\u00a0electromyography<\/a>\u00a0(EMG) and kinematic evaluation.\u00a0In both participants, tSCS reported a minimal improvement in voluntary movements still essential to start tSCS-enabled rehabilitation. Compared with tSCS, following EES showed immediate improvement in voluntary movements, whereas tSCS was more effective in improving balance and posture. Continuous improvement in nonmotor functions was found during tSCS-enabled and then during EES-enabled motor training. Results report a significant difference in the effect of tSCS and EES on the recovery of neurologic functions and support consecutive tSCS and EES applications as a potential therapy for SCI.\u00a0<\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n

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Our new manuscript “Evaluation of the Autologous Genetically Enriched Leucoconcentrate on the Lumbar Spinal Cord Morpho-Functional Recovery in a Mini Pig with Thoracic Spine Contusion Injury”<\/p>\n\n\n\n

Pathological changes associated with spinal cord injury can be observed distant, rostral, or caudal to the epicenter of injury.\u00a0The present study aimed to investigate the following in relation to SCI: distant changes in the spinal cord, peripheral nerve, and muscles. Here, we show the positive effect of autologous genetically enriched leucoconcentrate-producing recombinant neuroprotective factors on targets distant to the primary lesion site in mini pigs with SCI. These findings open new perspectives for the therapy of SCI<\/p>\n<\/div>\n\n\n\n

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New manuscript “Memristive circuit-based model of central pattern generator to reproduce spinal neuronal activity in walking pattern”. <\/p>\n\n\n\n

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Existing methods of neurorehabilitation include invasive or non-invasive stimulators that are usually simple digital generators with manually set parameters like pulse width, period, burst duration, and frequency of stimulation series. An obvious lack of adaptation capability of stimulators, as well as poor biocompatibility and high power consumption of prosthetic devices, highlights the need for medical usage of neuromorphic systems including memristive devices. The latter are electrical devices providing a wide range of complex synaptic functionality within a single element. In this study, we propose the memristive schematic capable of self-learning according to bio-plausible spike-timing-dependant plasticity to organize the electrical activity of the walking pattern generated by the central pattern generator.<\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n

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New study “Neurointerface with Oscillator Motifs for inhibitory
effect over antagonist muscles for compensation of
spastical syndrome”.<\/p>\n\n\n\n

The inhibitory management effect is usually underestimated in artificial control systems, using biological analogy. According to our hypothesis, the muscle hypertonus could
be effectively compensated via stimulation by bio plausible patterns. We proposed the approach for the compensatory
stimulation device in development of previously presented architecture of neurointerface, where neuroport is implemented as DAC and stimulator, neuroterminal \u2013 as neurosimulation
of a set of oscillator motifs on one-board computer.<\/p>\n<\/div>\n\n\n\n

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In the set of experiments with 5 volunteers we measured the efficacy of motor neuron inhibition via antagonist muscle or nerve stimulation registering muscle force with and without antagonist stimulation. For the agonist activation, we used both voluntary
activity and electrical stimulation. In the case of stimulation of both agonist and antagonist muscles and nerves, we experimented with delays between muscles stimulation starts in the range 0\u202620 ms. We registered the subjective discomfort rate. We didn\u2019t identify a significant difference between antagonist
muscle and nerve stimulation in both voluntary and stimulation of agonist activity. We determined the most effective delay between stimulation of agonist and antagonist muscle\/nerve as 10\u201320 ms.<\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n

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Our new manuscript\u00a0“Epidural electrical spinal cord stimulation of the thoracic segments (T2-T5) facilitates respiratory function in patients with complete spinal cord injury” is out in\u00a0Resp. Physiology & Neurobiology.<\/p>\n\n\n\n

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In this study, we assessed if the spinal cord Epidural\u00a0Electrical Stimulation<\/a>\u00a0(EES) at the segments T2-T5, related to\u00a0intercostal muscles<\/a>, can facilitate\u00a0respiratory function<\/a>\u00a0and particularly inspired\u00a0tidal volume<\/a>\u00a0during mechanic ventilation. Two patients with a high cervical injury were selected for this study with ethical committee permission and under review board supervision. A phrenic\u00a0nerve conduction study<\/a>\u00a0with diaphragm\u00a0electromyography<\/a>\u00a0(DEMG) was performed before and after trial of EES. Results demonstrate that EES at T2-T5 substantially increase the inspired volume. The results of this study also demonstrate that EES at spinal segments T2-T5 can bring patients dependent from\u00a0mechanical ventilation<\/a>\u00a0to pressure support (on CPAP), preventing Baro-trauma and other complications related to\u00a0mechanical ventilation<\/a>.<\/p>\n\n\n\n

These findings suggest that tested approach applied alone or in combination with the phrenic nerve stimulation could help to reduce time on\u00a0mechanical ventilation<\/a>\u00a0and related complications.<\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n

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Our new manuscript “Implementing Principles of Neuroontogenesis and Neuroplasticity for Spinal Cord Injury Therapy<\/strong>“<\/p>\n\n\n\n

Starting with the works of Santiago Ramon y Cajal, the problem of neuroregeneration remains one of the most important in neurobiology with still resonating the prophetic statement of Cajal:\u00a0\u201c\u2026once development was ended, the founts of growth and regeneration of the axons and dendrites dried up irrevocably. In adult centres the nerve paths are something fixed, ended, immutable. Everything may die, nothing may be regenerated. It is for the science of the future to change, if possible, this harsh decree\u201d<\/em><\/p>\n<\/div>\n\n\n\n

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Our manuscript “The Translesional Spinal Network and Its Reorganization after Spinal Cord Injury” is out in ‘The Neuroscientist’.<\/p>\n\n\n\n

Evidence from preclinical and clinical research suggest that neuromodulation technologies can facilitate the sublesional spinal networks, isolated from supraspinal commands after spinal cord injury (SCI), by reestablishing the levels of excitability and enabling descending motor signals via residual connections. Herein, we evaluate available evidence that sublesional and supralesional spinal circuits could form a\u00a0translesional spinal network<\/em>\u00a0after SCI.\u00a0<\/p>\n\n\n\n

We further discuss evidence of translesional network reorganization after SCI in the presence of sensory inputs during motor training. In this review, we evaluate potential mechanisms that underlie translesional circuitry reorganization during neuromodulation and rehabilitation in order to enable motor functions after SCI.\u00a0<\/p>\n<\/div>\n\n\n\n

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We discuss the potential of neuromodulation technologies to engage various components that comprise the translesional network, their functional recovery after SCI, and the implications of the concept of translesional network in development of future neuromodulation, rehabilitation, and neuroprosthetics technologies.<\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n

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New study “The Effect of Non-invasive Spinal Cord Stimulation on Anorectal Function in Individuals With Spinal Cord Injury: A Case Series” is out in Frontiers in Neuroscience.\u00a0<\/p>\n\n\n\n

Neurogenic bowel dysfunction (NBD) frequently occurs after a SCI leading to reduced sensation of bowel fullness and bowel movement often leading to constipation or fecal incontinence. Spinal Neuromodulation has been proven to be a successful modality to improve sensorimotor and autonomic function in patients with spinal cord injuries.\u00a0<\/p>\n<\/div>\n\n\n\n

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These pilot data represents the first demonstration of using spinal neuromodulation to activate the anorectal regions of patients with spinal cord injuries and the acute and chronic effects of stimulation. <\/p>\n\n\n\n

We observed that spinal stimulation induces contractions as well as changes in sensation and pressure profiles along the length of the anorectal region. In addition, we present a case report of a patient with a SCI and the beneficial effect of spinal neuromodulation on the patient\u2019s bowel program.<\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n

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Our new manuscript \u201cNew Therapy for Spinal Cord Injury: Autologous Genetically-Enriched Leucoconcentrate Integrated with Epidural Electrical Stimulation\u201d<\/a><\/em>  is out in Cells.<\/p>\n\n\n

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In this study, a novel regenerative approach using an autologous leucoconcentrate enriched with transgenes encoding VEGF, GDNF, and NCAM combined with supra- and sub-lesional epidural electrical stimulation was tested on mini-pigs. The analysis of the spinal cord recovery after a moderate contusion injury in treated mini-pigs compared to control animals revealed better performance in behavioral and joint kinematics, restoration of electromyography characteristics, and improvement in selected immunohistology features related to cell survivability, synaptic protein expression, and glial reorganization above and below the injury. <\/p>\n\n\n\n

These results for the first time demonstrate the positive effect of intravenous infusion of autologous genetically-enriched leucoconcentrate producing recombinant molecules stimulating neuroregeneration combined with neuromodulation by translesional multisite epidural stimulation on the restoration of the post-traumatic spinal cord in mini-pigs and suggest the high translational potential of this novel regenerative therapy for SCI patients. <\/p>\n\n\n\n

This work is a part of exciting long-term collaboration with Professor Islamov and his team.<\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n

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Our new study \u201cNewly regenerated axons via scaffolds promote sub-lesional reorganization and motor recovery with epidural electrical stimulation\u201d<\/em><\/a> is out in NPJ Regenerative Medicine<\/em>. This project was possible because of amazing efforts of Ahad and Riaz, fantastic collaboration with Dr. Windebank and Dr. Yaszemski, and hard work of all colleagues involved in this study!<\/p>\n\n\n\n

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In this study a combination of regenerative scaffold technology with spinal cord neuromodulation was validated and tested after complete spinal transection. Our results demonstrate that newly regenerated axons through the cell-containing scaffold with epidural electrical stimulation can reorganize sub-lesional circuitry and improve motor performance. <\/p>\n<\/div>\n\n\n\n

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The results of this work for the first time demonstrate that neuroregenerative therapy and neuromodulation cumulatively enhancing motor function after anatomically complete spinal cord injury, providing a platform for synergistic testing and translation of regenerative and neuromodulatory therapies to maximize functional restoration after severe spinal cord injury.<\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n

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Our new study \u201cPre-motor vs. motor cerebral cortex neuromodulation for chronic neuropathic pain\u201d<\/a><\/em>  is out in \u2018Scientific Reports<\/em>\u2019. <\/p>\n\n\n

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In this study we evaluate the role of electrode location on cerebral cortex in control of neuropathic pain and the role of trial stimulation in target\u2011optimization for the effect of subdural cerebral cortex stimulation. Locations of the temporary grid electrodes and permanent electrodes were evaluated in correlation with the long\u2011term efficacy of cortical stimulation in nine subjects with chronic neuropathic pain. <\/p>\n\n\n\n

Results demonstrate that the long\u2011term effect of subdural pre\u2011motor cortex stimulation is at least the same or higher compare to effect of motor or combined pre\u2011motor and motor cortex stimulation. These results also show that the initial trial stimulation helps to optimize permanent electrode positions in relation to the optimal functional target. <\/p>\n\n\n\n

Proposed methodology and novel results open a new potential for development of neuromodulation techniques to control chronic neuropathic pain.<\/p>\n\n\n\n

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Understanding of the spinal cord functional neuroanatomy is essential for diagnosis and treatment of multiple disorders including, chronic pain, movement disorders, and spinal cord injury. Although the role of the main spinal cord structures in neuromodulation therapy was broadly discussed, till now, there is no solid information on segment-specific distribution of the spinal roots and other spinal structures in humans. Previously we demonstrated the role of the spinal cord neuroanatomy \u0438n effect of epidural stimulation to evoke motor responses. Positioning the electrode close to the dorsal roots produced a significantly higher motor response than shift of the electrode from segment to segment. These results couldn\u2019t be collected on small models, like rats, due to different anatomy and we used a swine model to further translate these findings to human:<\/p>\n\n\n\n

https:\/\/www.frontiersin.org\/articles\/10.3389\/fnana.2017.00082\/full<\/a><\/p>\n\n\n

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The multiple aspects of the spinal cord anatomy are still unknown for humans. In our study published in Mayo Clinic Proceedings we collected neuroanatomical measurements of the spinal roots across the spinal cord segments, together with spinal cord and vertebral bones measurements on cadavers. A spatial orientation of the dorsal and ventral roots and spinal structures was correlated to selected bone landmarks. These results demonstrate less variability in rostral root angles compared to the caudal angles across all segments and different orientation of the dorsal and ventral rootlets at the cervical, thoracic, and lumbar segments. Additional information on segment-specific variation in number of rootlets and other spinal measurements was provided. We also demonstrate the strongest correlation between the length of intervertebral foramen to rostral rootlet and vertebral bone length.<\/p>\n\n\n\n

https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S0025619620310570<\/a><\/p>\n\n\n\n

As spinal cord neuromodulation strategies continue to evolve and novel spinal interfaces translated to clinical practice, the results of these studies will be important to precisely locate spinal roots and spinal cord structures for stimulation or surgical procedures. These results will help to improve stereotactic surgical procedures and electrode positioning for therapy of chronic pain, spinal cord injury and other conditions.<\/p>\n\n\n\n

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Our new study \u201cComparison of systemic and localized carrier-mediated delivery of methylprednisolone succinate for treatment of acute spinal cord injury\u201d<\/a><\/em><\/strong> published in Experimental Brain Research.<\/em> This work is based on early described the proof of principle of carrier-mediated administration for spinal cord injury.<\/strong><\/em><\/a><\/p>\n\n\n

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In new study we evaluate 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 spinal cord injury. Following local vs. systemic application, functional improvement was observed with MPS+TBS compared with either local or systemic MPS administration alone. The use of TBC carrier increased the active substance content in treated tissues by more than four times compare to either local or systemic MPS administration. <\/p>\n\n\n\n

These findings suggest that the local treatment of acute SCI could be enhanced with mixed micelles with TBC, increasing local drug accumulation, improving therapeutic outcome, and reducing side effects.<\/p>\n\n\n\n

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Our new manuscript “Epidural Stimulation Combined with Triple Gene Therapy for Spinal Cord Injury Treatment”<\/strong><\/em><\/a> <\/strong>has been published in IJMS and now is online.<\/p>\n\n\n

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Here we report\nfunctional restoration and morphological reorganization after spinal contusion\nin mini pigs, following a combined treatment of locomotor training facilitated\nwith epidural electrical stimulation (EES) and cell-mediated triple gene\ntherapy with umbilical cord blood mononuclear cells overexpressing recombinant\nvascular endothelial growth factor, glial-derived neurotrophic factor, and\nneural cell adhesion molecule. Results demonstrate positive effect of combined\nEES-facilitated motor training and cell-mediated triple gene therapy after\nspinal contusion in large animals, informing a background for further studies\nand clinical translation. This work is a product of long-term collaboration\nwith Professor Islamov and his team.<\/p>\n<\/div>\n\n\n\n

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A new manuscript “<\/em><\/a>Combined Supra- and Sub-Lesional Epidural Electrical Stimulation for Restoration of the Motor Functions after Spinal Cord Injury in Mini Pigs”<\/strong><\/a><\/em> <\/strong><\/a>is out in \u2018Brain Sciences\u2019<\/em>. <\/p>\n\n\n\n

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