Neuroprotective effects of sildenafil in experimental spinal cord injury in rabbits

Abstract

Neuroprotective agents such as methylprednisolone and sildenafil may limit damage after spinal cord injury. We evaluated the effects of methylprednisolone and sildenafil on biochemical and histologic changes after spinal cord injury in a rabbit model. Female New Zealand rabbits (32 rabbits) were allocated to 4 equal groups: laminectomy only (sham control) or laminectomy and spinal trauma with no other treatment (trauma control) or treatment with either methylprednisolone or sildenafil. Gelsolin and caspase-3 levels in cerebrospinal fluid and plasma were determined, and spinal cord histology was evaluated at 24 hours after trauma. There were no differences in mean cerebrospinal fluid or plasma levels of caspase-3 between the groups or within the groups from 0 to 24 hours after injury. From 0 to 24 hours after trauma, mean cerebrospinal fluid gelsolin levels significantly increased in the sildenafil group and decreased in the sham control and the trauma control groups. Mean plasma gelsolin level was significantly higher at 8 and 24 hours after trauma in the sildenafil than other groups. Histologic examination indicated that general structural integrity was better in the methylprednisolone in comparison with the trauma control group. General structural integrity, leptomeninges, white and grey matter hematomas, and necrosis were significantly improved in the sildenafil compared with the trauma control group. Caspase-3 levels in the cerebrospinal fluid and blood were not increased but gelsolin levels were decreased after spinal cord injury in trauma control rabbits. Sildenafil caused an increase in gelsolin levels and may be more effective than methylprednisolone at decreasing secondary damage to the spinal cord.

Evaluation of the efficacy of sildenafil citrate following severe head trauma in an experimental rat model

“…This indicates that tissue damage and apoptosis are reduced by sildenafil, which has been histologically proven in this study. Spinal hematoma and necrosis in white and gray matter were lesser in the rabbit group treated with sildenafil after trauma than in the control group; this finding supports the neuroprotective activity of sildenafil (17). In our study showing similar results, sildenafil citrate may have increased cerebral blood flow and decreased neuronal cell death at the cellular level during the acute phase through all these mechanisms, namely the NO-cGMP pathway.…”

“…The study conducted by Kara et al, wherein the abovementioned positive effects were also reported following spinal cord injury in rabbits, is remarkable (17). Kara et al reported that gelsolin level, which decreases during apoptosis resulting from conditions such as trauma, begins to increase in the cerebrospinal fluid in the acute phase after administering sildenafil in the early post-traumatic period.…”