Functional State of the Motor Centers of the Lumbar Spine after Contusion (Th8-Th9) with Application of Methylprednisolone-Copolymer at the Site of Injury

Spinal cord injuries must be treated as soon as possible. Studies of NASCIS protocols have questioned the use of methylprednisolone therapy. This study aimed to evaluate the effect of local delivery of methylprednisolone succinate in combination with a tri-block copolymer in rats with spinal cord injury. The experiments were conducted in accordance with the bioethical guidelines. We evaluated the state of the motor centers below the level of injury by assessing the amplitude of evoked motor responses in the hind limb muscles of rats during epidural stimulation. Kinematic analysis was performed to examine the stepping cycle in each rat. Trajectories of foot movements were plotted to determine the range of limb motion, maximum foot lift height, and lateral deviation of the foot in rats on the 21st day after spinal cord injury. We have shown that the local application of methylprednisolone succinate in combination with block copolymer leads to recovery of center excitability by 21 days after injury. In rats, they recovered weight-supported locomotion, directional control of walking, and balance. The proposed assessment method provides valuable information on gait disturbances following injury and can be utilized to evaluate the quality of therapeutic interventions.

[1]  T. Baltina,et al.  Morphofunctional Changes in the Spinal Cord of Rats after Contusion Injury with Local Delivery of Methylprednisolone in Combination with a Copolymer , 2023, Bulletin of Experimental Biology and Medicine.

[2]  Y. Gerasimenko,et al.  Plastic Changes Induced by Motor Activity in Spinal Cord Injury , 2023, Neuroscience and Behavioral Physiology.

[3]  T. Baltina,et al.  The Automatization of the Gait Analysis by the Vicon Video System: A Pilot Study , 2022, Sensors.

[4]  T. Baltina,et al.  Motor reorganization during simulation of gravitational unloading , 2022, 2022 Fourth International Conference Neurotechnologies and Neurointerfaces (CNN).

[5]  M. Baltin,et al.  Movement estimation methods based on the motion capture system , 2022, 2022 Fourth International Conference Neurotechnologies and Neurointerfaces (CNN).

[6]  Jiaming Liu,et al.  A Bibliometric Analysis of Publications on Spinal Cord Injury Treatment With Glucocorticoids Using VOSviewer , 2022, Frontiers in Public Health.

[7]  Tianjiao Zhang,et al.  Hydrogels in Spinal Cord Injury Repair: A Review , 2022, Frontiers in Bioengineering and Biotechnology.

[8]  A. Grumezescu,et al.  Novel Strategies for Spinal Cord Regeneration , 2022, International journal of molecular sciences.

[9]  Guixia Ling,et al.  Multimodal therapy strategies based on hydrogels for the repair of spinal cord injury , 2022, Military Medical Research.

[10]  J. Jeong,et al.  Review: Steroid Use in Patients With Acute Spinal Cord Injury and Guideline Update , 2022, Korean journal of neurotrauma.

[11]  Lin Zhu,et al.  Methylprednisolone Induces Neuro-Protective Effects via the Inhibition of A1 Astrocyte Activation in Traumatic Spinal Cord Injury Mouse Models , 2021, Frontiers in Neuroscience.

[12]  D. Burke,et al.  Silencing long ascending propriospinal neurons after spinal cord injury improves hindlimb stepping in the adult rat , 2021, bioRxiv.

[13]  Yuanyuan Huang,et al.  Zonisamide-loaded triblock copolymer nanomicelle as a controlled drug release platform for the treatment of oxidative stress -induced spinal cord neuronal damage , 2021 .

[14]  Igor A. Lavrov,et al.  Comparison of systemic and localized carrier-mediated delivery of methylprednisolone succinate for treatment of acute spinal cord injury , 2021, Experimental brain research.

[15]  Zhihong Zhong,et al.  Alkaline-phosphatase triggered self-assemblies enhances the anti-inflammatory property of methylprednisolone in spinal cord injury , 2020, Journal of applied biomaterials & functional materials.

[16]  P. Pranke,et al.  Nanotechnology for the treatment of spinal cord injury. , 2020, Tissue engineering. Part B, Reviews.

[17]  K. Gainutdinov,et al.  The Effects of Repeated Administration of the Micellar Complex of Methylprednisolone on the Locomotor Activity of a Terrestrial Snails , 2020, Bulletin of Experimental Biology and Medicine.

[18]  Jalilah Idris,et al.  Spinal Cord Injury: Pathophysiology, Multimolecular Interactions, and Underlying Recovery Mechanisms , 2020, International journal of molecular sciences.

[19]  M. Fehlings,et al.  The Functional Role of Spinal Interneurons Following Traumatic Spinal Cord Injury , 2020, Frontiers in Cellular Neuroscience.

[20]  L. Aglio,et al.  The safety and efficacy of steroid treatment for acute spinal cord injury: A Systematic Review and meta-analysis , 2020, Heliyon.

[21]  D. Baekey,et al.  Mid-cervical interneuron networks following high cervical spinal cord injury , 2020, Respiratory Physiology & Neurobiology.

[22]  K. Sharma,et al.  Neat Ionic liquid and α-Chymotrypsin-Polymer Surfactant Conjugate based Biocatalytic Solvent. , 2019, Biomacromolecules.

[23]  Dong Wang,et al.  Construction of rat spinal cord injury model based on Allen’s animal model , 2019, Saudi journal of biological sciences.

[24]  S. Choi,et al.  Incidence of acute spinal cord injury and associated complications of methylprednisolone therapy: a national population-based study in South Korea , 2019, Spinal Cord.

[25]  Da Yeon Kim,et al.  An Injectable Click-Crosslinked Hydrogel that Prolongs Dexamethasone Release from Dexamethasone-Loaded Microspheres , 2019, Pharmaceutics.

[26]  Andrew R. Brown,et al.  From cortex to cord: motor circuit plasticity after spinal cord injury , 2019, Neural regeneration research.

[27]  W. Young,et al.  Clinical Neurorestorative Therapeutic Guidelines for Spinal Cord Injury (IANR/CANR version 2019) , 2019, Journal of orthopaedic translation.

[28]  Igor A. Lavrov,et al.  Multifactorial motor behavior assessment for real-time evaluation of emerging therapeutics to treat neurologic impairments , 2019, Scientific Reports.

[29]  K. Takagishi,et al.  Spontaneous functional full recovery from motor and sensory deficits in adult mice after mild spinal cord injury , 2019, Heliyon.

[30]  S. Karimi-Abdolrezaee,et al.  Traumatic Spinal Cord Injury: An Overview of Pathophysiology, Models and Acute Injury Mechanisms , 2019, Front. Neurol..

[31]  Jian Li,et al.  NEP1-40-modified human serum albumin nanoparticles enhance the therapeutic effect of methylprednisolone against spinal cord injury , 2019, Journal of Nanobiotechnology.

[32]  Bo Chen,et al.  Reactivation of Dormant Relay Pathways in Injured Spinal Cord by KCC2 Manipulations , 2018, Cell.

[33]  N. Petrova,et al.  Self-assembled nanoformulation of methylprednisolone succinate with carboxylated block copolymer for local glucocorticoid therapy. , 2018, Colloids and surfaces. B, Biointerfaces.

[34]  Atefeh Ghavidast,et al.  Advances in nanomicelles for sustained drug delivery , 2017 .

[35]  M. Sargon,et al.  Localized delivery of methylprednisolone sodium succinate with polymeric nanoparticles in experimental injured spinal cord model , 2017, Pharmaceutical development and technology.

[36]  D. Parker The Lesioned Spinal Cord Is a “New” Spinal Cord: Evidence from Functional Changes after Spinal Injury in Lamprey , 2017, Front. Neural Circuits.

[37]  Allan R. Martin,et al.  A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Use of Methylprednisolone Sodium Succinate , 2017, Global spine journal.

[38]  M. Kawamata,et al.  Changes in synaptic transmission of substantia gelatinosa neurons after spinal cord hemisection revealed by analysis using in vivo patch-clamp recording , 2016, Molecular pain.

[39]  B. Kundu,et al.  Methylprednisolone for acute spinal cord injury: an increasingly philosophical debate , 2016, Neural regeneration research.

[40]  Igor A. Lavrov,et al.  Non-invasive topical drug delivery to spinal cord with carboxyl-modified trifunctional copolymer of ethylene oxide and propylene oxide. , 2016, Colloids and surfaces. B, Biointerfaces.

[41]  B. Kundu,et al.  Patients with Spinal Cord Injuries Favor Administration of Methylprednisolone , 2016, PloS one.

[42]  R. Shi,et al.  Nanomedicine strategies for treatment of secondary spinal cord injury , 2015, International journal of nanomedicine.

[43]  K. Fouad,et al.  Anatomical correlates of recovery in single pellet reaching in spinal cord injured rats , 2013, Experimental Neurology.

[44]  S. Rossignol,et al.  Treadmill training promotes spinal changes leading to locomotor recovery after partial spinal cord injury in cats. , 2013, Journal of neurophysiology.

[45]  K. Schaser,et al.  Current Practice of Methylprednisolone Administration for Acute Spinal Cord Injury in Germany: A National Survey , 2013, Spine.

[46]  N. Theodore,et al.  Pharmacological therapy for acute spinal cord injury. , 2013, Neurosurgery.

[47]  R. Stein,et al.  Effect of percutaneous stimulation at different spinal levels on the activation of sensory and motor roots , 2012, Experimental Brain Research.

[48]  W. Chiu,et al.  Autophagy Is Activated in Injured Neurons and Inhibited by Methylprednisolone After Experimental Spinal Cord Injury , 2012, Spine.

[49]  I. Cuthill,et al.  Reporting : The ARRIVE Guidelines for Reporting Animal Research , 2010 .

[50]  Sylvie Nadeau,et al.  Spontaneous Motor Rhythms of the Back and Legs in a Patient With a Complete Spinal Cord Transection , 2010, Neurorehabilitation and neural repair.

[51]  A. Varejão,et al.  Methylprednisolone fails to improve functional and histological outcome following spinal cord injury in rats , 2009, Experimental Neurology.

[52]  A. Schröter,et al.  High-dose corticosteroids after spinal cord injury reduce neural progenitor cell proliferation , 2009, Neuroscience.

[53]  Qingli Xiao,et al.  STAT5 Mediates Antiapoptotic Effects of Methylprednisolone on Oligodendrocytes , 2009, The Journal of Neuroscience.

[54]  R. Franklin,et al.  Quantification of deficits in lateral paw positioning after spinal cord injury in dogs , 2008, BMC veterinary research.

[55]  D. DuBois,et al.  Pharmacokinetics of methylprednisolone after intravenous and intramuscular administration in rats , 2007, Biopharmaceutics & drug disposition.

[56]  R. Shi,et al.  Neuroprotection from secondary injury by polyethylene glycol requires its internalization , 2007, Journal of Experimental Biology.

[57]  Michael G Fehlings,et al.  Pharmacological approaches to repair the injured spinal cord. , 2006, Journal of neurotrauma.

[58]  Sang Keun Park,et al.  Effects of Methylprednisolone on the Neural Conduction of the Motor Evoked Potentials in Spinal Cord Injured Rats , 2005, Journal of Korean medical science.

[59]  Paul J. Reier,et al.  Morphological changes of the soleus motoneuron pool in chronic midthoracic contused rats , 2005, Experimental Neurology.

[60]  M. Rathbone,et al.  Ait-082 and Methylprednisolone Singly, but Not in Combination, Enhance Functional and Histological Improvement after Acute Spinal Cord Injury in Rats , 2004, International journal of immunopathology and pharmacology.

[61]  Abbas F Jawad,et al.  Effects of limb exercise after spinal cord injury on motor neuron dendrite structure , 2004, The Journal of comparative neurology.

[62]  Martin E Schwab,et al.  The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats , 2004, Nature Neuroscience.

[63]  P. Gardiner,et al.  Passive exercise and fetal spinal cord transplant both help to restore motoneuronal properties after spinal cord transection in rats , 2004, Muscle & nerve.

[64]  Alexander V Kabanov,et al.  Optimal Structure Requirements for Pluronic Block Copolymers in Modifying P-glycoprotein Drug Efflux Transporter Activity in Bovine Brain Microvessel Endothelial Cells , 2003, Journal of Pharmacology and Experimental Therapeutics.

[65]  A. Kabanov,et al.  Pluronic block copolymers: novel functional molecules for gene therapy. , 2002, Advanced drug delivery reviews.

[66]  M. Uchiba,et al.  Methylprednisolone reduces spinal cord injury in rats without affecting tumor necrosis factor-alpha production. , 2001, Journal of neurotrauma.

[67]  Volker Dietz,et al.  Efficient testing of motor function in spinal cord injured rats , 2000, Brain Research.

[68]  J. Liaw,et al.  Evaluation of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) gels as a release vehicle for percutaneous fentanyl. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[69]  C. Bernards,et al.  Spinal Cord Bioavailability of Methylprednisolone after Intravenous and Intrathecal Administration: The Role of P-Glycoprotein , 2000, Anesthesiology.

[70]  Ian Q. Whishaw,et al.  Ground reaction forces in locomoting hemi-parkinsonian rats: a definitive test for impairments and compensations , 1999, Experimental Brain Research.

[71]  M. Dimitrijevic,et al.  Evidence for a Spinal Central Pattern Generator in Humans a , 1998, Annals of the New York Academy of Sciences.

[72]  H. Winn,et al.  Administration of Methylprednisolone for 24 or 48 Hours or Tirilazad Mesylate for 48 Hours in the Treatment of Acute Spinal Cord Injury: Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial , 1998 .

[73]  D. Basso,et al.  A sensitive and reliable locomotor rating scale for open field testing in rats. , 1995, Journal of neurotrauma.

[74]  M. Conterato A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. , 1991, The New England journal of medicine.

[75]  W. Collins,et al.  A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. , 1991, The New England journal of medicine.

[76]  M. Bracken,et al.  The Second National Acute Spinal Cord Injury Study. , 1990, Journal of neurotrauma.

[77]  Alfred Reginald Allen,et al.  SURGERY OF EXPERIMENTAL LESION OF SPINAL CORD EQUIVALENT TO CRUSH INJURY OF FRACTURE DISLOCATION OF SPINAL COLUMN: A PRELIMINARY REPORT , 1911 .

[78]  E. Kalkan,et al.  The effects of steroids in traumatic thoracolumbar junction patients on neurological outcome. , 2019, Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery : TJTES.

[79]  J. Schwab,et al.  Determinants of Axon Growth, Plasticity, and Regeneration in the Context of Spinal Cord Injury. , 2018, The American journal of pathology.

[80]  Igor A. Lavrov,et al.  EFFECTS OF LOCAL HYPOTHERMIA ON SPINAL CORD INJURY IN RATS , 2018 .

[81]  Mohammad Amjad Kamal,et al.  Recent Advances in Drug Delivery of Polymeric Nano-Micelles. , 2017, Current drug metabolism.

[82]  N. Theodore,et al.  Pharmacological Therapy for Acute Spinal Cord Injury. , 2015, Neurosurgery.

[83]  Bingbing Song,et al.  Recovery of supraspinal control of stepping via indirect propriospinal relay connections after spinal cord injury , 2008, Nature Medicine.

[84]  Ranu Jung,et al.  Activity-dependent plasticity in spinal cord injury. , 2008, Journal of rehabilitation research and development.

[85]  M. London,et al.  Dendritic computation. , 2005, Annual review of neuroscience.