Neuroprotective effect of tempol (4-hidroxi tempo) after axonotmesis of motor roots in the CNS and PNS interface

Abstract

Motor root crushing, or axonotmesis, is an important medical problem and may occur due to intervertebral disc herniation, spinal stenosis, and tumors. The crushing, although it causes serious clinical signs, is less severe than avulsion, since the continuity between the CNS and PNS is maintained, facilitating the subsequent regeneration. Metabolic modifications on astrocytes and microglia in early post-lesion stages, the so-called glial reactivity, play a dual role in the lesion's microenvironment. Sometime after the lesion, astrocytes have an inhibitory function when it comes to regeneration, promoting glial scar formation. Most part of neuronal death happens due to apoptotic mechanisms and oxidative stress. Therefore, many antioxidant drugs are being studied in the hope of minimizing these events. Among these drugs, Tempol has shown promising results in attenuating the effects of reactive oxygen species. In this respect, the present study intends to evaluate the effects of Tempol on medullary motoneuron survival and also on astrocytes and microglia reactivity, in adult Sprague-Dawley rats after crushing the ventral roots L4, L5, and L6. The rats will be divided into two groups: (1) ventral root crushing and intraperitoneal injection with saline solution and (2) ventral root crushing and intraperitoneal injection with Tempol. After the survival of 14 days, the animals will be sacrificed. The neuronal survival will be evaluated by the Nissl staining method and the immunohistochemistry technique will be used to evaluate the expression of GFAP and Iba-1, which are, respectively, astrocytes and microglia markers. (AU)