Modulation of spinal reactive gliosis following peripheral nerve injury (PNI) is a promising strategy to restore synaptic homeostasis. Oxidized ATP (OxATP), a nonselective antagonist of purinergic P2X receptors, was found to recover a neuropathic behavior following PNI. We investigated the role of intraperitoneal (i.p.) OxATP treatment in restoring the expression of neuronal and glial markers in the mouse spinal cord after sciatic spared nerve injury (SNI). Using in vivo two-photon microscopy, we imaged Ca(2+) transients in neurons and astrocytes of the dorsal horn of spinal cord at rest and upon right hind paw electrical stimulation in sham, SNI, and OxATP-treated mice. Neuropathic behavior was investigated by von Frey and thermal plantar test. Glial [glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (Iba1)] and GABAergic [vesicular GABA transporter (vGAT) and glutamic acid decarboxylase 65/76 (GAD65/67)] markers and glial [glutamate transporter (GLT1) and GLAST] and neuronal amino acid [EAAC1, vesicular glutamate transporter 1 (vGLUT1)] transporters have been evaluated. In SNI mice, we found (i) increased glial response, (ii) decreased glial amino acid transporters, and (iii) increased levels of neuronal amino acid transporters, and (iv) in vivo analysis of spinal neurons and astrocytes showed a persistent increase of Ca(2+) levels. OxATP administration reduced glial activation, modulated the expression of glial and neuronal glutamate/GABA transporters, restored neuronal and astrocytic Ca(2+) levels, and prevented neuropathic behavior. In vitro studies validated that OxATP (i) reduced levels of reactive oxygen species (ROS), (ii) reduced astrocytic proliferation, (iii) increase vGLUT expression. All together, these data support the correlation between reactive gliosis and perturbation of the spinal synaptic homeostasis and the role played by the purinergic system in modulating spinal plasticity following PNI.
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http://dx.doi.org/10.1007/s12035-014-8943-y | DOI Listing |
Arch Orthop Trauma Surg
January 2025
Orthopedics Research Center, Mashhad University of Medical Science, Mashhad, Iran.
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January 2025
Division of Neurosurgery, Department of Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
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Cell Biochem Funct
January 2025
Stem Cells & Biotherapy Engineering Research Center of Henan, College of Life Science and Technology, Xinxiang Medical University, Xinxiang, China.
Spinal cord injury (SCI) is a common neurological trauma that cannot be completely cured with surgical techniques and medications. In this study, we established a mouse SCI model and used an adeno-associated virus (AAV) to achieve the high expression of sonic hedgehog (Shh) at the injury site to further investigate the therapeutic effect and mechanism of Shh on SCI. The results of the present study show that Shh may promote motor function recovery.
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Division of Reconstructive Microsurgery Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Background: High-level median or ulnar nerve injuries and repairs typically result in suboptimal re-innervation of distal muscles. Functioning Free Muscle Transplantation (FFMT) is increasingly recognized as an effective method to restore function in chronic muscle denervation cases. This study investigates the efficacy of using an additional FFMT, neurotized by lateral sprouting axons from a repaired high-level mixed nerve in the upper limb, to enhance distal hand function.
View Article and Find Full Text PDFCNS Neurosci Ther
January 2025
School of Pharmacy, Nantong University, Nantong, Jiangsu, China.
Aims: N-Demethylsinomenine (NDSM) demonstrates good analgesic efficacy in preclinical pain models. However, how NDSM exerts analgesic actions remains unknown.
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