Effect of tempol (4-hydroxy-tempo) on synaptic plasticity, regeneration and inflammation after the crushing of ventral roots in the CNS and PNS interface

Abstract

High energy accidents, as well as obstetric injuries can lead to traction, crush or avulsion of the spinal cord roots, generating extensive functional losses. The pathophysiology of the lesion includes modifications of synapses in the injured neurons, glutamatergic excitotoxicity, glial reaction and the release of reactive oxygen species (ROS). The central nervous system (CNS) is easily damaged by ROS because of its high lipid constitution and absence of highly efficient antioxidant defense mechanisms. Therefore, several researches have evaluated the neuroprotective efficacy of pharmacological agents with antioxidant activity in CNS lesions. Among the antioxidant studied drugs stands out Tempol. Recent studies demonstrate that Tempol has a neuroprotective effect in sciatic traumatic injury in neonate rats increasing the survival of medullary motoneurons. The present study analyzes the effect of Tempol in synaptic plasticity, glutamatergic excitotoxicity, modulation of the inflammation and motor recovery, after crushing the ventral roots L4, L5 and L6 in female Sprague-Dawley adult rats. The animals will be divided into two experimental groups (n=5, per experimental group): (1) crushing of the ventral roots L4, L5 and L6 and intraperitoneal administration of saline solution (PBS); (2) crushing of the ventral roots, L4, L5 and L6 and intraperitoneal administration of Tempol (12 mg/kg). By immunohistochemical technique, two weeks after injury, the expression of GAD65, VGLUT1 and CD3 will be analyzed, which are, respectively, GABAergic synapses, glutamatergic synapses and T lymphocytes markers. Through the walking track test (Catwalk), during eight weeks after injury, the animals' motor recovery will be evaluated. (AU)