Inosine Improves Functional Recovery and Cell Morphology Following Compressive Spinal Cord Injury in Mice.

Abstract

Spinal cord injury (SCI) is one of the most serious conditions of the central nervous system, causing motor and sensory deficits that lead to a significant impairment in the quality of life. Previous studies have indicated that inosine can promote regeneration after SCI. Here we investigated the effects of inosine on the behavioral and morphological recovery after a compressive injury. Adult female C57BL/6 mice were subjected to laminectomy and spinal cord compression using a vascular clip. Inosine or saline injections were administered intraperitoneally, with the first dose performed 24 h after injury and daily for 7 days after injury. The mice were evaluated using Basso Mouse Scale (BMS), locomotor rating scale, and pinprick test for 8 weeks. At the end, the animals were anesthetized and euthanized, and the spinal cords were collected for morphological evaluation. Inosine-treated animals presented better results in the immunostaining for oligodendrocytes and in the number of myelinated fibers through semithin sections compared to saline-treated animals, showing that there was a greater preservation of the white matter. Analysis of the immunoreactivity of astrocytes and evaluation of the inflammatory profile with macrophage labeling revealed that the animals of the inosine group had a lower immunoreactivity when compared to control, which suggests a reduction of the glial scar and less inflammation, respectively, leading to a more favorable microenvironment for spinal cord regeneration. Indeed, inosine-treated animals scored higher on the BMS scale and presented better results on the pinprick test, indicating that the treatment contributed to motor and sensory recovery. After the animals were sacrificed, we obtained the electroneuromyography, where the inosine group showed a greater amplitude of the compound muscle action potential. These results indicate that inosine contributed to the regeneration process in the spinal cord of mice submitted to compressive injury and should be further investigated as a candidate for SCI therapy.