Early decompression of the injured optic nerve reduces axonal degeneration and improves functional outcome in the adult rat

Abstract

The putative beneficial role of an early decompression of injured CNS tissue following trauma remains controversial. In this study, we approach this scientific query using a standardized injury of the optic nerve in adult rats. Adult Sprague-Dawley rats were subjected to a standardized optic nerve constriction injury by applying a loose ligature around the nerve for 5 min, 1, 6 or 24 h. All animals were sacrificed at 28 dpi. Viable axons distal to the injury were quantified using semithin sections, and regenerative fibers were studied using antisera to neurofilament and GAP43. Axonal degeneration and glial scar development were analyzed using Fluoro-Jade staining and anti-GFAP, respectively. Visual function was studied with visual evoked potentials (VEP). No significant differences were observed between 1 and 6 h of optic nerve compression. However, the number of viable axons analyzed with neurofilament and on semithin sections, decreased significantly between 6 and 24 h, paralleled by an increase in Fluoro-Jade labeled axonal debris (P < 0.001). GFAP-IR density was significantly higher (P < 0.001) in the 24 h compression group in comparison to 6 h. VEP showed preserved, but impaired visual function in animals subjected to compression up to 6 h, compared to an abolished cortical response at 24 h. Regenerative GAP43-positive sprouts were occasionally found distal to the lesion in animals subjected to compression up to 6 h, but not at 24 h. These findings suggest that early optic nerve decompression within hours after the initial trauma is beneficial for functional outcome.