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    The effects of resveratrol on vasospasm after experimental subarachnoidal hemorrhage in rats
    (ELSEVIER SCIENCE INC, 2008) Karaoglan, Alper; Akdemir, Osman; Barut, Seref; Kokturk, Sibel; Uzun, Hafize; Tasyurekli, Mustafa; Colak, Ahmet
    Background: Cerebral vasospasin remains a major cause of morbidity and mortality in patients with SAH. Although many pharmacologic agents and chemicals have been used to prevent and treat CV, the pathogenesis of that condition has not been established. We investigated the efficacy of resveratrol, a stilbene polyphenol and tyrosine kinase inhibitor that occurs naturally in grapes and red wine, in a murine basilar artery vasospasm model. Methods: Forty-two Wistar albino rats were used in this study. The rats were divided into 3 groups of 14 animals each: the sham-operated control group (group 1), the vasospasm group (group 2), and the treatment group (group 3). In groups 2 and 3, autologous blood (0.3 mL) was injected into the cisterna magna. After that injection, the rats in group 3 received an intravenous injection of resveratrol (10 mg/kg) for 72 hours. The evaluation of the response to both the injection of autologous blood and treatment was based on biochemical markers in tissue and serum and on light microscopic findings from the basilar artery, which were collected at different intervals after experimental SAH. Results: Endothelin-1 levels in brain tissue and serum were higher in the vasospasin group than in the control group (P < .05). In group 3 rats, the administration of resveratrol resulted in significantly lower ET-1 values than those in group 2. Brain and serum lipid peroxidation levels were markedly elevated in group 2 rats but decreased significantly after resveratrol treatment in group 3 rats (P < .05). Superoxide dismutase expression in brain tissue and scrum was lower in group 2 rats than in sham-operated controls, and a significant increase in the SOD level was associated with resveratrol treatment. On examination via light microscopy 72 hours after SAH, the mean perimeters of the arterial lumen in groups 1, 2, and 3 were 719 +/- 16, 411.6 +/- 9, and 590.1 +/- 5.6 mu m, respectively. The mean thickness of the arterial wall was as follows: in group 1, 11.1 +/- 0.8 mu m; in group 2, 16.1 +/- 1.2 mu m; and (after resveratrol treatment) in group 3, 13.4 +/- 0.6 mu m Conclusions: The results Of Our study showed that resveratrol induced the relaxation of smooth muscle in the wall of the basilar artery and may be provided with neuroprotection against cerebral ischemia in a rat model. These effects may be associated with the antioxidant and vasodilatory effects of resveratrol, which could prove to be an agent prophylactic against CV and to be therapeutic for individuals who experience that event. (C) 2008 Elsevier Inc. All rights reserved.
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    Therapeutic efficacy of SJA6017, a calpain inhibitor, in rat spinal cord injury
    (ELSEVIER SCI LTD, 2008) Akdemir, Osman; Ucankale, Murat; Karaoglan, Alper; Barut, Seref; Sagmanligil, Ayhan; Bilguvar, Kaya; Cirakoglu, Beyazit; Sahan, Elife; Colak, Ahmet
    Apoptosis is an important element of the secondary processes that occur after spinal cord injury. Calpain and caspases are key proteases in apoptotic death. We evaluated the neuroprotective effects of SJA6017 (a calpain inhibitor) and measured functional recovery in a rat spinal cord injury model. Thirty Wistar albino rats were divided into three groups of 10 animals each: sham-operated (group 1), trauma control (group 2) and trauma-plus-SJA6017 treatment (group 3). Spinal cord trauma was produced in the thoracic region of the animals. Rats in group 3 received SJA6017 1 min after trauma. Treatment efficacy was evaluated after injury using light microscopy and TUNEL staining. Neurological performance was assessed using a inclined plane and a modified version of the Tarlov's grading scale. Group 2 rats showed moderate traums with widespread edema, hemorrhage, vascular thrombi and necrosis 24 h after injury. Group 3 rats had significantly reduced tissue injury and apoptosis. Tarlov scores revealed that group 3 rats also had ameliorated recovery of limb function. Our results demonstrate that treatment with SJA6017 reduces apoptotic cell death, preserves spinal cord tissue and improves functional outcome. Treating calpain-induced apoptosis with this agent may be a feasible therapeutic strategy for patients with spinal cord injury. (c) 2007 Elsevier Ltd. All rights reserved.