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Yayın AR-A014418 as a glycogen synthase kinase-3 inhibitor: Anti-apoptotic and therapeutic potential in experimental spinal cord injury(ELSEVIER DOYMA SL, 2013) Tuncdemir, Matem; Yildirim, Aziz; Karaoglan, Alper; Akdemir, Osman; Ozturk, MelekObjectives: We aimed to investigate the effects of AR-A014418, a strong inhibitor specific to GSK-3beta, on neuronal apoptosis and neuroprotection in the traumatic SCI model. Materials and methods: In this study, three groups were generated from 36 Wistar rats; (1) control, (2) spinal cord trauma group created by clip compression technique after laminectomy, and (3) AR-A014418 (4mg/kg, i.p., DMSO) treatment group after laminectomy and spinal cord trauma. The TUNEL assay for apoptosis detection, immunohistochemical staining for bax and TGF-beta were applied in spinal cord tissues. For light microscopic examination, necrotic, and apoptotic cells were counted, and PMNL counting was applied to detect inflammation. Functional recovery was tested by field locomotor test in the 3rd and 7th days following surgery. Results: In the trauma group, diffuse hemorrhage, cavitation, necrosis and edematous regions, degeneration in motor neurons and leukocyte infiltration were observed in gray matter. In the AR-A014418-treated groups, healthy cells were observed in more places compared to the trauma groups, however, cavitation, hemorrhagic, and edematous areas were seen in gray matter. In the AR-A014418-treatment groups, the number of apoptotic cells in the 3rd and 7th days (respectively; p<0.05, p<0.01), were significantly decreased compared to the trauma groups, as were the levels of bax (p<0.01) and TGF-beta 1 immunoreactivity. Results of the locomotor test were significantly increased in the treatment group (p<0.001) as compared to the trauma group. Conclusions: In this experimental spinal cord trauma model study neural apoptosis was significantly triggered in secondary damage developed after trauma, however, neurological healing was expedited by preventing mitochondrial apoptosis and reducing the inflammation by the potent inhibitor AR-A014418, which is GSK-3beta selective. 2011 Sociedad Espanola de Neurocirugia. Published by Elsevier Espana, S.L. All rights reserved.Yayın Bilateral epidural hematoma in a patient with human immunodeficiency virus infection: a case report(TURKISH ASSOC TRAUMA EMERGENCY SURGERY, 2013) Kelten, Bilal; Karaoglan, Alper; Cal, Mehmet Alpay; Akdemir, Osman; Karanci, TurkerIntracranial epidural haematomas are almost always secondary to head traumas and usually occur unilaterally. Bilateral intracranial epidural haematomas are rare, but the mortality is very high. In our case, we report a bilateral epidural haematoma in a 32 year old, HIV infected male patient who came to the emergency service with a head trauma because of a motor vehicle-pedestrian accident. The occurrence of bilateral epidural haematoma in an HIV infected patient is a rare condition as a result of head trauma in a lateral direction on one side. As a result of the vasculopathy and coagulopathy, which are complications of HIV infection, the cerebral vessels have a fragile structure that leads to complications that facilitate the development of contralateral intracranial epidural haematoma together.Yayın Correlation between leptin and pro-inflammatory cytokines in cortical contusion injury model(TURKISH ASSOC TRAUMA EMERGENCY SURGERY, 2011) Karaoglan, Alper; Akdemir, Osman; Cinar, Nilgun; Cal, Mehmet Alpay; Kelten, Bilal; Uzun, Hafize; Colak, AhmetBACKGROUND The present study aimed to investigate time-dependent changes in leptin concentrations in brain tissue following experimental traumatic brain injury and to examine the relationship with cytokines. METHODS After circular craniectomy, 33 male Wistar-albino rats were positioned on a stereotaxic frame and subjected to cortical contusion injury and then divided into 3 groups based on the depth of deformation as: 0 mm (sham controls, n=3), 1.5 mm (moderate injury, n=15) and 2.7 mm (severe injury, n=15). Animals were sacrificed on the 1st, 3rd and 5th days post-injury. RESULTS One day after moderate injury, interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), and leptin levels were found to be markedly increased in the brain tissue. On the 3rd and 5th days, the levels returned to the sham-control levels. Following severe injury, IL-1 beta, IL-6 and TNF-alpha levels increased in correlation after the 1st day and reached the sham-control levels on the same days. However, leptin tissue levels decreased on the 1st and 3rd days and normalized to the sham-control levels on the 5th day. CONCLUSION Our results showed that the release of leptin is decreased in the early stage of severe injury. Thus, leptin replacement may play an important role in therapy in cases with severe traumatic brain injury.Yayın Effects of 4% Icodextrin on Experimental Spinal Epidural Fibrosis(TURKISH NEUROSURGICAL SOC, 2017) Karanci, Turker; Kelten, Bilal; Karaoglan, Alper; Cinar, Nilgun; Midi, Ahmet; Antar, Veysel; Akdemir, Hidayet; Yalcinkaya Kara, Zeynep MineAIM: The aim of this experimental study was to investigate whether spinal epidural 4% glucose polymer solution is effective in the prevention of postoperative' ibrosis. MATERIAL and METHODS: Twenty eight adult Wistar albino rats were randomly divided into two equal groups, including treatment and control. Both groups underwent L1 vertebral total laminectomy to expose the dura. Topical treatment group received 4% icodextrin. Four weeks later, epidural fibrosis was examined in both groups histologically, biochemically and macroscopically. RESULTS: Topical use of 4% icodextrin prevented significantly epidural fibrosis following the laminectomy operation. CONCLUSION: Topical 4% icodextrin application inhibits postoperative epidural fibrosis with various mechanisms and prevents adhesions by playing barrier role between tissue surfaces through flotation. Our study is first to present evidence of experimental epidural fibrosis prevention with 4% icodextrin.Yayın The Effects of Difumarate Salt S-15176 after Spinal Cord Injury in Rats(KOREAN NEUROSURGICAL SOC, 2015) Erdogan, Hakan; Tuncdemir, Matem; Kelten, Bilal; Akdemir, Osman; Karaoglan, Alper; Tasdemiroglu, ErolObjective : In the present study we analyzed neuroprotective and antiapoptotic effect of the difumarate salt S-15176, as an anti-ischemic, an antioxidant and a stabilizer of mitochondrial membrane in secondary damage following spinal cord injury (SCI) in a rat model. Methods : Three groups were performed with 30 Wistar rats; control (1), trauma (2), and a trauma+S-15176 (10 mg/kg i.p., dimethyl sulfoxide) treatment (3). SCI was performed at the thoracic level using the weight-drop technique. Spinal cord tissues were collected following intracardiac perfusion in 3rd and 7th days of posttrauma. Hematoxylin and eosin staining for histopatology, terminal deoxynucleotidyl transferase dUTP nick end labeling assay for apoptotic cells and immunohistochemistry for proapoptotic cytochrome-c, Bax and caspase 9 were performed to all groups. Functional recovery test were applied to each group in 3rd and 7th days following SCI. Results : In trauma group, edematous regions, diffuse hemorrhage, necrosis, leukocyte infiltration and severe degeneration in motor neurons were observed prominently in gray matter. The number of apoptotic cells was significantly higher (p<0.05) than control group. In the S-15176-treated groups, apoptotic cell number in 3rd and 7th days (p<0.001), also cytochrome-c (p<0.001), Box (p<0.001) and caspase 9 immunoreactive cells (p<0.001) were significantly decreased in number compared to trauma groups. Hemorrhage and edema in the focal areas were also noticed in gray matter of treatment groups. Results of the locomotor test were significantly increased in treatment group (p<0.05) when compared to trauma groups. Conclusion : We suggest that difumarate salt S-15176 prevents mitochondrial pathways of apoptosis and protects spinal cord from secondary injury and helps to preserve motor function following SCI in rats.Yayın 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, AhmetBackground: 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.Yayın Erector spinae plane block as the main anesthetic method for peri-paravertebral area surgical procedure(ELSEVIER SCIENCE INC, 2019) Tulgar, Serkan; Yildirim, Aziz; Karaoglan, Alper; Ozer, Zeliha…Yayın Hemostasis vs. epidural fibrosis?: A comparative study on an experimental rat model of laminectomy(TERMEDIA PUBLISHING HOUSE LTD, 2016) Erdogan, Hakan; Kelten, Bilal; Tuncdemir, Matem; Erturkuner, Salime Pelin; Uzun, Hafize; Karaoglan, AlperAim: The aim of this study was to evaluate the histopathological and biochemical impact and effectiveness of two hemostatic agents, Ankaferd blood stopper (ABS) and Microporous Polysaccharide Hemospheres (MPH), on epidural fibrosis in an experimental rat laminectomy model. Material and methods: Twenty adult Wistar albino rats were divided into MPH-treated (n = 6), ABS-treated (n = 6) and control (n = 8) groups. Laminectomy of the lumbar spine was performed in all animals and treatment groups were exposed to MPH and ABS while closure was applied in control group as per usual. Epidural fibrosis was evaluated in all groups macroscopically, histopathologically, biochemically and with electron microscopy four weeks later. Results: Statistically, it was found that MPH-treated group had significantly less epidural fibrosis compared to ABS-treated and control groups. Conclusion: We compared two hemostatic agents for their propensity to cause adhesions in the present study. Our results show that MPH significantly reduces epidural scar formation and dural adhesion in a rat model of laminectomy while ABS increases postoperative fibrosis. (C) 2016 Polish Neurological Society. Published by Elsevier Sp. z o.o. All rights reserved.Yayın Intramuscular Hematomas Caused by Anticoagulant Therapy: Is Advanced Age a Risk Factor?(GALENOS YAYINCILIK, 2010) Cinar, Nilgun; Sahin, Sevki; Karaoglan, Alper; Karsidag, SibelOral anticoagulant therapy (OAT) is very effective in the prevention of cerebral embolism, especially in certain cardiac diseases. Hematomas are the major complication of OAT. It may threaten the patient's life by bleeding into the vital structures. Herein, we describe four patients with hematomas in the psoas, quadriceps, pectoral, or rectus abdominis muscles accompanied by anemia during warfarin therapy for atrial fibrillation and artificial heart valves. Computed tomography and magnetic resonance imaging helped us establish a definitive diagnosis in each case. Our patients were three women and one man. Their international normalized ratios were within the therapeutic range during this period. They suffered from minor traumas, such as falls or a hit while taking warfarin therapy. All anticoagulation treatments were discontinued for approximately 1 week after the episode of bleeding. Although conservative management was sufficient for three patients, one patient had surgical decompression due to a rectus abdominis hematoma with retroperitoneal hemorrhage. There were no episodes of bleeding or other complications after starting oral anticoagulant therapy during the follow-up. The common aspects of our cases were older age and a history of minor trauma. As a result, we suggest that special attention needs to be paid to the patients under anticoagulant therapy, especially those at an advanced age, and to warn them avoid trauma. (Archives of Neuropsychiatry 2010;47:267-70)Yayın Pentoxifylline Inhibits Epidural Fibrosis in Post-Laminectomy Rats(INT SCIENTIFIC LITERATURE, INC, 2016) Kelten, Bilal; Erdogan, Hakan; Antar, Veysel; Sanel, Selim; Tuncdemir, Matem; Kutnu, Muge; Karaoglan, Alper; Orki, TulayBackground: The aim of this experimental study was to investigate the effectiveness of intramuscular pentoxifylline in the prevention of postoperative fibrosis. Material/Methods: We divided 16 adult Wistar albino rats into 2 equal groups: treatment and control. Both groups underwent L1 vertebral total laminectomy to expose the dura. The intramuscular treatment group received pentoxifylline. Four weeks later, epidural fibrosis was studied in both groups using electron microscopy, light microscopy, histology, biochemistry, and macroscopy. Results: The evaluation of epidural fibrosis in the 2 groups according to macroscopic (p<0.01) assessment and light microscopy revealed that epidural scar tissue formation was lower in the treatment group compared to the control group (p<0.001) and the number of fibroblasts was also decreased significantly in the pentoxifylline-treated group (p<0.05). More immature fibers were demonstrated in the treatment group by electron microscopy in comparison with the control group. In biochemical analysis, a statistically significant decrease was detected in hydroxyproline, which indicates fibrosis and myeloperoxidase activity, and shows an inflammatory response (P<0.001). Conclusions: Systemic pentoxifylline application prevents postoperative epidural fibrosis and adhesions with various mechanisms. Our study is the first to present evidence of experimental epidural fibrosis prevention with pentoxifylline.Yayın A Rare Emergency Condition in Neurosurgery: Foot Drop Due to Paget's Disease(TURKISH NEUROSURGICAL SOC, 2009) Karaoglan, Alper; Akdemir, Osman; Erdogan, Hakan; Colak, AhmetPaget's disease is a chronic, focal skeletal disorder that usually affects the pelvis and spine. Spinal cases are generally asymptomatic; in the symptomatic cases, the neurological dysfunctions are related to non-compressive vascular defects, hemorrhage, sarcomatoid degeneration, spinal stenosis, or pathological fractures, primarily in the lumbar region. The Neurosurgeon should have a fundamental understanding of the complications of Paget's disease and should be familiar with the indications for treatment, as well as available medical and surgical therapies. In the present paper, we report a case of Paget's disease that presented with an isolated foot drop due to a pathological fracture of L5 vertebra, and then discuss the therapeutic strategies presented in the literature.Yayın Solitary Cerebellar Metastasis from a non-muscle Invasive Transitional Cell Carcinoma of Bladder(JOURNAL NEUROLOGICAL SCIENCES, 2015) Kelten, Bilal; Ekici, Sinan; Erdogan, Hakan; Sinanoglu, Orhun; Yener, Nese; Karaoglan, AlperBrain metastasis from non muscle invasive transitional cell carcinoma of the urinary bladder occurs very rarely. Herein, a patient who underwent transurethral resection of bladder tumor and received intravesical bacillus Calmette- Guerin for pT1, G3 bladder carcinoma accompanied by carcinoma in situ, and who subsequently developed solitary cerebellar metastasis following 18 months cystoscopic follow-up period with normal findings was reported. To our knowledge, only two cases of solitary cerebellar metastasis from pT1 bladder cancer was reported in the English literature.Yayın 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, AhmetApoptosis 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.