Purinergic Modulation of Spinal Neuroglial Maladaptive Plasticity Following Peripheral Nerve Injury.

Mol Neurobiol

Laboratory of Neuronal Networks, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, via L. Armanni, 5, 80138, Naples, Italy.

Published: December 2015

AI Article Synopsis

  • The study explores how modifying spinal reactive gliosis can help restore balance in the nervous system after peripheral nerve injury (PNI).
  • Oxidized ATP (OxATP), which blocks certain receptors, was shown to improve neuropathic behaviors by affecting glial and neuronal marker expression in mouse spinal cords following nerve injury.
  • Results indicated that OxATP treatment reduced glial activation, normalized calcium levels in neurons and astrocytes, and alleviated symptoms of neuropathic pain, suggesting its potential as a therapeutic approach.

Article Abstract

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.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12035-014-8943-yDOI Listing

Publication Analysis

Top Keywords

nerve injury
12
neuropathic behavior
12
amino acid
12
modulation spinal
8
peripheral nerve
8
reactive gliosis
8
synaptic homeostasis
8
spinal cord
8
neurons astrocytes
8
neuronal amino
8

Similar Publications

Introduction: There exist conflicting electrodiagnostic reports between diagnosing mild carpal tunnel syndrome (CTS) and normal results, depending on the interpretation methods used by electrodiagnosticians. This underscores the necessity for precise clinical guidelines. This study aims to assess how the variation between mild and normal electrophysiological reports impacts (1) subsequent clinical outcomes in patients diagnosed with CTS and (2) physicians' decision-making.

View Article and Find Full Text PDF

Purpose: We sought to evaluate the incidence, natural history, and management of cystic spinal lesions following myelomeningocele/myeloschisis closure.

Methods: We performed a single-center retrospective review of all patients who underwent myelomeningocele/myeloschisis closure from 2013 to 2018 with follow-up to 5 years old.

Results: We analyzed 100 fetal repairs and 81 postnatal closures from 305 total surgeries.

View Article and Find Full Text PDF

Shh Protects the Injured Spinal Cord in Mice by Promoting the Proliferation and Inhibiting the Apoptosis of Nerve Cells via the Gli1-TGF-β1/ERK Axis.

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.

View Article and Find Full Text PDF

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 PDF

Aims: N-Demethylsinomenine (NDSM) demonstrates good analgesic efficacy in preclinical pain models. However, how NDSM exerts analgesic actions remains unknown.

Methods: We examined the analgesic effects of NDSM using both pain-evoked and pain-suppressed behavioral assays in two persistent pain models.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!