Negative Impact of Sigma-1 Receptor Agonist Treatment on Tissue Integrity and Motor Function Following Spinal Cord Injury

Abstract

In traumatic spinal cord injury, the initial trauma is followed by a cascade of impairments, including excitotoxicity and calcium overload, which ultimately induces secondary damages. The sigma-1 receptor is widely expressed in the central nervous system and is acknowledged to play a key role in calcium homeostasis. Treatments with agonists of the sigma-1 receptor induce beneficial effects in several animal models of neurological diseases. In traumatic injury the use of an antagonist of the sigma-1 receptor reversed several symptoms of central neuropathic pain. Here, we investigated whether sigma-1 receptor activation with PRE-084 is beneficial or detrimental following SCI in mice. First, we report that PRE-084 treatment after injury does not improve motor function recovery. Second, using ex vivo diffusion weighted magnetic resonance imaging completed by histological analysis, we highlight that σ1R agonist treatment after SCI does not limit lesion size. Finally, PRE-084 treatment following SCI decreases NeuN expression and increases astrocytic reactivity. Our findings suggest that activation of sigma-1 receptor after traumatic spinal cord injury is detrimental on tissue preservation and motor function recovery in mice.

Reduced GFAP Expression in Bergmann Glial Cells in the Cerebellum of Sigma-1 Receptor Knockout Mice Determines the Neurobehavioral Outcomes after Traumatic Brain Injury

“…Interestingly, after genetic inactivation and pharmacological blockade of S1R, antinociceptive effects on mice with traumatic spinal cord injury (SCI) were detected [ 17 ]. On the other hand, activation of S1R after SCI is presumed to be detrimental for neuron survival and motor function recovery [ 18 ]. Thus, different S1R ligands may exert various effects in a variety of neurodegenerative disease models.…”

Therapeutic Effect of Exosomes Derived From Stem Cells in Spinal Cord Injury: A Systematic Review Based on Animal Studies

“…Spinal cord injury (SCI) is a devastating disease that can result in impaired sensorimotor function, defects in the autonomic nervous system, and neuropathic pain ( 1 ). The annual incidence of SCI is as high as 15–40 cases per 100,000, and the global mortality rate of hospitalized patients with acute SCI is as high as 4.4–16.7, which is on the rise worldwide ( 2 ).…”

Exosomes Derived from Nerve Stem Cells Loaded with FTY720 Promote the Recovery after Spinal Cord Injury in Rats by PTEN/AKT Signal Pathway

“…Spinal cord injury (SCI) is a common and harmful injury in spinal surgery with 0.6-0.9 million new patients worldwide every year [1]. Symptoms of SCI range from minimal dysfunction to quadriplegia and consist entirely of sensory, motor, and autonomic dysfunction [2]. Usually, after the primary traumatic mechanical destruction of the spinal cord tissues, secondary damage was rapidly triggered, such as inflammation, hypoxia, ischemia, and neuronal apoptosis [3].…”