Evaluation of the Effect of Nandrolone Decanoate on Experimental Spinal Cord Injury in Rats

Abstract

Background: Acute spinal cord injury, a common cause of neurological dysfunction in humans and animals, impairs motor, sensory and autonomic functions and may result in permanent disability. Nandrolone decanoate (ND) is a steroid widely studied for its predominantly anabolic effect and low androgenic potential. Several researchers have described the positive interference of ND in neurological tissue, such as increased synthesis and release of neurotrophic substances, but to date no studies have evaluated the action of this steroid in acute spinal cord injury. The aim of this study was therefore to evaluate the effect of ND in rats subjected to acute spinal cord injury. 

Materials, Methods & Results: Thirty-two young adult Wistar rats (Rattus norvegicus), weighing between 240 and 260 g, were divided into three groups. The first group (GNAN) (n=13) was subjected to acute spinal cord injury and treated with ND; the control group (GCON) (n=13) was subjected to spinal cord injury without treatment; and the third group (GLAM) (n=6) underwent laminectomy without prior spinal cord injury, in order to control changes caused by the procedure. A 20 g metal device was released from a height of 25 cm to produce the spinal cord injury. After exposing the spinal canal, a 2-mm diameter metal rod was placed directly in contact with the spinal cord, and when the weight was released, the rod was struck, causing the spinal cord injury. An intramuscular injection of 2 mg/kg of ND was administered the immediate postoperative period. The animals were assessed to ascertain the recovery of their motor function on five occasions, namely at 24 h, 48 h, 72 h, 7 and 14 days after undergoing spinal cord injury. This assessment was performed using the Basso, Beattie and Bresnahan (BBB) model. The animals were euthanized 14 days post-op and fragments of the spinal cord and urinary bladder were collected for histological evaluation. 

Discussion: The animals subjected to spinal cord injury presented paraplegia, failing to score on the BBB scale in the first three assessments. Starting 7 days after surgery, the GNAN (0-13) and GCON (0-5) groups gradually began showing locomotor improvements, with scale variations. On day 14 after spinal cord injury, 22% of the animals in GNAN and 11% in GCON had failed to recover their locomotor function, scoring zero on the BBB scale. After spinal cord injury, all the animals showed urine retention. The urinary function returned on average on day 5 post surgery, with no significant difference between the groups. The locomotor assessment of the animals subjected to acute spinal cord injury revealed that the injury varied in intensity in GNAN and GCON, with signs of pelvic limb paraplegia and asymmetric non-ambulatory paraparesis. Time was a determining factor in the clinical evolution of the animals, with no evidence of the influence of ND. The histological findings revealed variations in the intensity of the injury, with a tendency for lower intensity in the cranial and epicentral segments of the lesion in the animals subjected to ND treatment, albeit without statistically significant evidence (P ≥ 0.05). The spinal cord assessments of the GLAM group indicated that the surgical procedure did not cause histological alterations, since the normal architecture of the neural tissue was preserved. The histopathological evaluations of the urinary bladder revealed an inflammatory response characterized by lymphohistiocytosis and neutrocytosis in the animals of GNAN and GCON, without interference of ND in the change (P ≥ 0.05). The method to elicit spinal cord injury reproduced functional, sensory and motor incapacity heterogeneously in rats. In the dose evaluated here, ND did not significantly influence the return of locomotor function and the intensity of spinal cord histopathological alterations.