Anti-inflammatory and Antiapoptotic Effect of Interleukine-18 Binding Protein on the Spinal Cord Ischemia-Reperfusion In

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Anti-inflammatory and Antiapoptotic Effect of Interleukine-18 Binding Protein on the Spinal Cord Ischemia-Reperfusion Injury Ergün Karavelioğlu,1 Yücel Gönül,2 Serdar Kokulu,3,8 Ömer Hazman,4 Fatih Bozkurt,5 Ahmet Koçak,6 and Olcay Eser7

Abstract—We investigated the anti-inflammatory and antiapoptotic effects of interleukin-18 binding protein (IL-18BP) on spinal cord ischemia/reperfusion (I/R) injury in rats. Twenty-one adult male rats were divided into three groups: sham, I/R, and I/R+IL-18BP. Proinflammatory cytokines were determined in rat blood samples by using ELISA, while apoptosis was immunohistochemically evaluated in spinal cord tissue using caspase 3. Both IL-18 and TNF-α were significantly decreased in the IL-18BP group compared to that in the sham group. The highest caspase 3 levels were observed in the I/R group, while the lowest levels were found in the sham group. The mean Tarlov score of the I/R group was significantly lower than that of the sham group. However, the mean Tarlov score of the IL-18BP group was significantly higher than that of the I/R group. The results of the current study demonstrate that IL18BP plays both anti-inflammatory and antiapoptotic roles in spinal cord I/R injury. KEY WORDS: interleukin-18 binding protein; spinal cord; ischemia-reperfusion; cytokines; caspase 3.

INTRODUCTION Ischemic spinal cord injury, the cause of severe neurological sequelae, may have either traumatic or nontraumatic origins; several etiologies play a role in this process. It is well established that thoracoabdominal aortic surgery and aortic cross-clamping present high risks of 1

Department of Neurosurgery, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey 2 Department of Anatomy, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey 3 Department of Anesthesia and Reanimation, Faculty of Medicine, Afyon Kocatepe University, İzmirYolu 8. km, Afyonkarahisar, Turkey 4 Department of Chemistry, Faculty of Science and Arts, Afyon Kocatepe University, Afyonkarahisar, Turkey 5 Department of Pathology, Faculty of Veterinary, Afyon Kocatepe University, Afyonkarahisar, Turkey 6 Department of Histology, Faculty of Medicine, Dumlupınar University, Kütahya, Turkey 7 Department of Neurosurgery, Faculty of Medicine, Balıkesir University, Balıkesir, Turkey 8 To whom correspondence should be addressed at Department of Anesthesia and Reanimation, Faculty of Medicine, Afyon Kocatepe University, İzmirYolu 8. km, Afyonkarahisar, Turkey. E-mail: [email protected]

spinal cord ischemia/reperfusion (I/R) injury with rates that range between 4 and 33 % [5, 7, 12]. Neurological damage such as tissue necrosis and loss of function due to compression, distraction, and laceration at the time of insult is called “primary injury.” After primary injury in spinal cord damage, secondary insults could then be caused by activation of endogenous substances. Although the exact biomechanism of spinal cord I/R injury is not fully understood, inflammation, apoptosis, and oxygen-derived free radicals