Functional and Structural Recovery of the Injured Spinal Cord in Rats Treated with Gonadotropin-Releasing Hormone

Abstract

Several studies have shown that gonadotropin-releasing hormone (GnRH) have extra-pituitary roles, including neurotrophic effects. This study was to evaluate the effects of GnRH treatment on the spinal cord injury (SCI) of rats. Ovariectomized rats were divided into: sham SCI surgery (Sham), SCI treated with saline solution (SCI + SS), and SCI treated with GnRH (SCI + GnRH). The SCI was induced by compression. One day after the lesion, SCI + GnRH group was injected with GnRH (60 µg/kg/twice/day; i.m.) for 15 days and the other groups with saline solution. To kinematic gait analysis, length and velocity of the stride were measured. In spinal cord, axonal morphometry and spared white and gray matter were analyzed by histochemistry. Protein expression of spinophilin was evaluated by western blot. The results showed that, 5 weeks after the injury, the group of animals treated with GnRH, significantly increased the length and velocity of the stride compared to SCI + SS group and they were similar to Sham group. In spinal cord, GnRH treatment increased the number and caliber of nerve axons and in the case of white matter, spared tissue was significantly higher than those animals treated with saline solution. The expression of spinophilin in spinal cord of SCI + GnRH group was slightly increased with respect to those not treated. In conclusion, GnRH treatment improves recovery of gait and decreases histopathological damage in the injured spinal cord of rat. These findings suggest that GnRH acts as a neurotrophic factor and can be used as a potential therapeutic agent for treatment of SCI.

Low dose exposure to Bisphenol A alters development of gonadotropin-releasing hormone 3 neurons and larval locomotor behavior in Japanese Medaka

“…These data suggest possible roles of GnRH3 systems on locomotion or movement. Interestingly, studies on spinal cord injury also support locomotor effects of GnRH systems, showing that GnRH treatment to rats with experimentally induced spinal cord injury improves recovery, increases locomotor activity, and decreases histopathological damage in the injured spinal cord of rats (Calderon-Vallejo et al, 2015;Calderon-Vallejo and Quintanar, 2012).…”

“…Previous studies of spinal cord injury in rat models have used GnRH as a treatment for locomotion recovery (Calderon-Vallejo et al, 2015;Calderon-Vallejo and Quintanar, 2012). We tested the effects of a GnRH inhibitor (RFRP3) on locomotor behavior to examine if impacting the GnRH system would affect locomotion of 20 dpf larvae.…”

Neurological improvement in patients with chronic spinal cord injury treated with leuprolide acetate, an agonist of GnRH

“…In relation to the functional effects of GnRH and LA, locomotion activity was evaluated in rats with SCI. The results showed a partial but significantly improvement in locomotor activity and gait related to stride length and stride speed (Calderón-Vallejo et al 2015, Calderón-Vallejo and Quintanar 2012, Díaz-Galindo et al 2015. Quintanar et al (2016b) reported a case of a male patient with chronic incomplete spinal cord injury (ASIA C) at level T-9 treated with LA during 12 months.…”

“…In the morphological study of spinal cord, both GnRH and LA treatment increased the number and caliber of nerve axons, and the white matter was well preserved in SCI rats (Calderón-Vallejo et al 2015, Díaz-Galindo et al 2015. In SCI, the plasticity of axons can be gained through processes of regeneration, where new axonal growth arises at the injury site from the cut end of an axon.…”

“…In vitro, GnRH incubation induced changes in outgrowth, number and length of neurites in rat cerebral cortical neurons and spinal cord neurons Salinas 2008, Quintanar et al 2016a). In vivo, administration of GnRH improves locomotor activity and bladder function, and increases the expression of neurofilaments in spinal cord in rats with SCI (Calderón-Vallejo et al 2015, Calderón-Vallejo and. Likewise, the administration of LA im-proves locomotor activity, gait, micturition reflex and spinal cord morphology in rats with SCI (Díaz-Galindo et al 2015).…”