 Neuroprotective effects of sildenafil in experimental spinal cord injury in rabbits_Hasan Kara

38BOSNIAN JOURNALOF BASIC MEDICAL SCIENCES WWW.BJBMS.ORGINTRODUCTIONTraumatic spinal cord injury (SCI) negatively af f ects the quality of life of patients and their families and mostly af f ects younger adults. Th ese injuries severely disturb motor, sensory, and autonomic functions. In most cases, complete neurologic recovery cannot be achieved in patients who experience SCI, even though advanced surgical techniques are available.T h e biochemical changes and pathophysiology after SCI have been investigated in order to develop treatments that may minimize function loss. Th e biphasic injury process in SCI includes a primary phase with localized acute bleeding and ischemia and a secondary phase with edema, electrolyte alterations, occurrence of oxygen free radicals, inf l ammation, lipid peroxidation, and apoptosis [1-4].As in other central nervous system diseases, apoptosis is the most common type of cell death, mediated by caspase, and highly related to the pathologic loss of neurons, astrocytes, and oligodendrocytes [5]. Caspase levels are increased in SCI because cell death in the spinal cord increases posttransla-tional activation of caspases [6]. Caspase-3 levels are increased in tissue samples of rats that have experimental SCI [7].Gelsolin, an actin-binding plasma protein, is an important mediator of apoptosis. Gelsolin might cause changes in cell morphology and motility. When actin is released from injured cells, circulating gelsolin begins to clear the actin. Normal plasma gelsolin levels are 200 to 300 mg/L. During apoptosis, gelsolin is cleaved by caspase-3, and gelsolin levels decrease. Th e N-terminal gelsolin fragment (39 kDa) increases apop-tosis [8]. Plasma gelsolin levels may decrease below normal *Corresponding author: Hasan Kara, Selcuk University, Faculty of Medicine, Department of Emergency Medicine, Konya, Turkey, Tel: +90 505 2112473, Fax: +90 332 224 4858. E-mail: hasankara42@gmail.comSubmitted: 31 August 2014 / Accepted: 08 October 2014Neuroprotective ef f ects of sildenaf i l in experimental spinal cord injury in rabbitsHasan Kara 1 *, Selim Degirmenci 1 , Ahmet Ak 1 , Aysegul Bayir 1 , Seyit Ali Kayis 2 , Mehmet Uyar 3 , Murat Akinci 1 , Demet Acar 1 , Metin Kocacan 4 , Fikret Akyurek 51 Department of Emergency Medicine, Faculty of Medicine, Selcuk University, Konya, Turkey. 2 Department of Animal Science, Faculty of Agriculture, Selcuk University, Konya, Turkey. 3 Department of Public Health, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey. 4 Department of Histology and Embryology, Faculty of Medicine, Selcuk University, Konya, Turkey. 5 Department of Biochemistry, Faculty of Medicine, Selcuk University, Konya, TurkeyAbstractNeuroprotective agents such as methylprednisolone and sildenaf i l may limit damage after spinal cord injury. We evaluated the ef f ects of meth-ylprednisolone and sildenaf i l 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 sildenaf i l. Gelsolin and caspase-3 levels in cerebrospinal fl uid and plasma were determined, and spinal cord histology was evaluated at 24 hours after trauma. Th ere were no dif f erences in mean cerebrospinal fl uid 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 cere-brospinal fl uid gelsolin levels signif i cantly increased in the sildenaf i l group and decreased in the sham control and the trauma control groups. Mean plasma gelsolin level was signif i cantly higher at 8 and 24 hours after trauma in the sildenaf i l than other groups. Histologic examination indicated that general structural integrity was better in the methylprednisolone in comparison with the trauma control group. General struc-tural integrity, leptomeninges, white and grey matter hematomas, and necrosis were signif i cantly improved in the sildenaf i l compared with the trauma control group. Caspase-3 levels in the cerebrospinal fl uid and blood were not increased but gelsolin levels were decreased after spinal cord injury in trauma control rabbits. Sildenaf i l caused an increase in gelsolin levels and may be more ef f ective than methylprednisolone at decreasing secondary damage to the spinal cord.KEY WORDS: Caspase-3, gelsolin, methylprednisolone, phosphodiesterase type 5, traumaDOI: http://dx.doi.org/10.17305/bjbms.2015.1.119 Bosn J Basic Med Sci. 2015;15(1):38-44. © 2015 ABMSFBIHRESEARCH ARTICLE