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Öğe Boric Acid Suppresses Glioblastoma Cellular Survival by Regulating Ferroptosis via SOX10/GPx4/ACSL4 Signalling and Iron Metabolism(Wiley, 2025) Kilic, Guven; Hacioglu, Ceyhan; Tuncer, Cengiz; Kar, Ezgi; Kar, Fatih; Taskesen, Ahmet; Kurtulus, AdemFerroptosis, a distinct form of regulated cell death, plays a role in glioma pathogenesis. SRY-box (SOX) transcription factors are key regulators of cancer progression. In this study, we investigated the role of SOX10 in ferroptosis induction in U87 cells following boric acid treatment. First, the cytotoxic effects of boric acid on HMC3 and U87 cells were assessed using CCK8 and BrdU incorporation assays. Subsequently, SOX10, GPX4, ACSL4, GSH, MDA, total ROS, Fe2+, and TFR levels were analysed using ELISA, Western blot, and RT-PCR techniques. Additionally, DAPI staining was performed to evaluate nuclear abnormalities. According to the CCK8 analysis, the IC50 value for boric acid was determined to be 3.12 mM for HMC3 cells and 532 mu M for U87 cells, a finding further supported by BrdU incorporation analysis, which indicated that U87 cells were more sensitive to boric acid. Western blot and RT-PCR analyses revealed that SOX10 expression was significantly higher in U87 cells compared to HMC3 cells. Boric acid treatment led to a reduction in GSH, GPX4, and SOX10 levels in U87 cells, while inducing an increase in MDA, total ROS, ACSL4, Fe2+, and TFR levels. Moreover, microscopic analysis demonstrated that boric acid treatment induced both morphological and nuclear abnormalities in U87 cells. In conclusion, our findings demonstrate that SOX10 is involved in the ferroptosis signalling pathway and that boric acid effectively suppresses U87 cell viability by targeting the SOX10/GPX4/ACSL4 axis.Öğe The Comparative Effects of Anakinra and Tocilizumab on Inflammation and Cerebral Vasospasm in an Experimental Subarachnoid Hemorrhage Model(Mdpi, 2024) Kilic, Guven; Engin, Berk Enes; Halabi, Amir; Tuncer, Cengiz; Sungur, Mehmet Ali; Alpay, Merve; Kurtulus, AdemObjective: Subarachnoid hemorrhage (SAH) is a life-threatening cerebrovascular condition that triggers a robust inflammatory response and cerebral vasospasm. This study aimed to evaluate the effects of anakinra, an interleukin-1 receptor antagonist, and tocilizumab, an interleukin-6 receptor antagonist, on inflammation and vasospasm in an experimental rat SAH model. Methods: Forty male Sprague Dawley rats (200-250 g) were randomly assigned to five groups: control, SAH, SAH + anakinra (ANA), SAH + tocilizumab (TCZ), and SAH + anakinra + tocilizumab (ANA+TCZ). SAH was induced by injecting non-heparinized arterial blood into the cisterna magna. Treatment groups received anakinra (50 mg/kg twice daily), tocilizumab (8 mg/kg once daily), or their combination for three days. Blood and cerebrospinal fluid (CSF) samples were analyzed for inflammatory markers (IL-1, IL-6, TNF-alpha, CRP), and histopathological evaluations were conducted to assess vasospasm and apoptosis. Results: SAH significantly increased pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha, CRP) and fibrinogen levels in serum and CSF while reducing the basilar artery lumen diameter (p < 0.001). Anakinra and tocilizumab treatments significantly reduced inflammatory markers and vasospasm severity compared to the SAH group (p < 0.05). Combination therapy was more effective in reducing inflammation and vasospasm than either treatment alone (p < 0.05). Anakinra showed a stronger effect on IL-1 reduction, while tocilizumab was more effective in lowering IL-6 levels. The ANA+TCZ group exhibited a significant decrease in caspase activity, indicating reduced apoptosis (p < 0.05). Conclusions: Anakinra and tocilizumab effectively mitigated inflammation and vasospasm in an experimental SAH model, with combination therapy showing superior efficacy. These findings suggest that targeting both IL-1 and IL-6 pathways may be a promising therapeutic strategy for managing SAH complications. Further studies are warranted to evaluate long-term outcomes and clinical implications.Öğe Factors Affecting Resorption Following Cranioplasty with an Autologous Bone Graft(Turkish Neurosurgical Soc, 2024) Yuruk, Burak; Tekiner, Ayhan; Erdem, Yavuz; Celik, Haydar; Yildirim, Mehmet Emre; Kurtulus, Adem; Sahin, OmerAIM: To evaluate the relationship between the surgical techniques, the waiting time for surgery, postoperative distance between the graft-bone margin and the percentage of bone resorption, we analyzed patients who underwent cranioplasty. Cranioplasty is a necessary surgery to preserve brain tissue and provide an appropriate microenvironment. MATERIAL and METHODS: In this study, patients who underwent autologous bone grafting after decompressive craniectomy by the Neurosurgery Clinic of University of Health Sciences Ankara Training and Research Hospital between 2018 and 2021 were examined. RESULTS: Thirty-nine patients who underwent autologous cranioplasty following decompressive craniectomy were included in the study. The average expected time for cranioplasty surgery following decompressive craniectomy was 16.97 +/- 13.478 weeks (min:2 max:62 weeks). The expected time between decompressive craniectomy and cranioplasty surgeries and resorption rates were compared. The resorption rate was above 30% in 7 of 10 patients with 24 weeks or more between craniectomy and cranioplasty, and less than 30% in 17 of 25 patients in surgeries less than 24 weeks (p=0.04). Following cranioplasty surgery, the distance between the graft-bone margin and the resorption rates were also compared. In this analysis, statistically significant differences were detected between the distance between the graft-bone border and the resorption rates. Resorption rates increased in 15 of 19 patients with a postcranioplasty distance of 1 mm or more (p<0.00001). CONCLUSION: Early cranioplasty surgery is important in order to reduce complications that may occur after craniectomy. In addition, it is important to keep the defect area small in size during craniectomy surgery and to keep the cutting edge thinner when the bone graft is taken, in order to reduce the development of bone graft resorption.Öğe Mitigating Post-Subarachnoid Hemorrhage Complications: Anti-Inflammatory and Anti-Apoptotic Effects of Anakinra in an Experimental Study(Mdpi, 2025) Kilic, Guven; Engin, Berk Enes; Halabi, Amir; Tuncer, Cengiz; Sungur, Mehmet Ali; Alpay, Merve; Kurtulus, AdemBackground: Subarachnoid hemorrhage (SAH) is a severe neurological condition with high mortality and morbidity rates, often exacerbated by secondary complications such as inflammation, cerebral vasospasm, and apoptosis. Proinflammatory cytokines, including interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6), play critical roles in these pathological processes. Anakinra, an IL-1 receptor antagonist, has demonstrated significant anti-inflammatory effects in various disease models. This study aimed to evaluate the efficacy of anakinra in mitigating inflammation, vasospasm, and apoptosis in an experimental rat model of SAH. Methods: Thirty-two male Sprague Dawley rats were divided into four groups: Control (healthy), SAH (no treatment), Saline (0.2 mL saline subcutaneously), and Anakinra (50 mg/kg subcutaneously, twice daily). Proinflammatory markers (CRP, TNF-alpha, IL-1, IL-6, and fibrinogen) were measured in serum and cerebrospinal fluid (CSF) at 3, 7, and 10 days post-SAH. Basilar artery diameter was evaluated histopathologically, and Caspase-3 expression was assessed immunohistochemically to determine apoptotic activity. Results: SAH significantly increased levels of CRP, TNF-alpha, IL-1, IL-6, and fibrinogen in both serum and CSF, reduced basilar artery diameter, and elevated Caspase-3 expression compared to the Control group. Saline treatment provided limited improvements, with inflammatory markers and histopathological parameters remaining elevated. Anakinra treatment significantly reduced inflammatory markers, restored basilar artery diameter, and lowered Caspase-3 expression, highlighting its efficacy in mitigating inflammation, vasospasm, and apoptosis. Conclusions: Anakinra effectively suppresses inflammation, alleviates cerebral vasospasm, and inhibits apoptosis in an experimental model of SAH. These findings suggest its potential as a therapeutic agent for managing SAH and its complications. Further research is needed to explore its clinical applicability and long-term effects.Öğe Retrospective Examination of Patients with Spontaneous Cranial Intracerebral Hematoma(Turkish Neurosurgical Soc, 2024) Cengiz, Serdar; Erdem, Yavuz; Celik, Haydar; Tekiner, Ayhan; Kul, Halil; Kurtulus, Adem; Yildirim, Mehmet EmreAIM: To investigate the relationship among the modified Rankin scores of patients who had intracerebral hematomas at discharge, demographic characteristics of the patients, and the characteristics of the hematoma. MATERIAL and METHODS: In this study, patients diagnosed with intracerebral hematoma and treated at the Ministry of Health Ankara Training and Research Hospital Neurosurgery Clinic between January 2010 and December 2020 were examined retrospectively. The age, gender, comorbidity, anticoagulant-antiaggregant use, and Glasgow Coma Scale score of the patients were obtained from hospital records. The modified Rankin scale (mRS) was used to assess patients at discharge. RESULTS: Herein, a total of 114 patients with supratentorial intracerebral hematoma were evaluated. The modified Rankin score ranged from 0 to 6, with a mean score of 3.47 +/- 2.26. When the patients were evaluated based on their discharge status, the mortality rate was 33.3% (n=38). Fifty percent of the patients who used anticoagulant-antiaggregant died. High mRS scores were seen more frequently in advanced age. Among the other diseases of the patients, hypertension and the use of anticoagulant- antiaggregant were found to be statistically significant with high mRS scores (p<0.001). Patients with low Glasgow Coma Scale score at the time of admission had significantly higher mRS scores (p<0.001). CONCLUSION: Patients with advanced age, hypertension, and anticoagulant-antiaggregant use had a higher mRS score after hematoma formation. Preventable risk factors for spontaneous intraparenchymal hematomas are among the leading causes of disability, and early detection and treatment of underlying diseases are critical for hematoma prevention. Awareness about risk factors should be the priority to improve early diagnosis and reduce treatment disability rates.Öğe Retrospective Examination of the PECARN Algorithm in Pediatric Patients with Minor Head Trauma(Duzce Univ, Fac Medicine, 2025) Dinc, Samet; Kurtulus, Adem; Coban, Necmettin; Tuncer, Cengiz; Tekiner, AyhanObjective: We aimed to retrospectively evaluate and examine pediatric head trauma cases according to PECARN in the light of their neurological and clinical conditions. We wanted to contribute to the detection of TBI with minimum CT imaging rates in order to avoid radiation-related carcinogenesis. Method: 108 pediatric patients who were admitted to the emergency department due to minor head trauma and were admitted to the neurosurgery clinic were evaluated retrospectively. Results: During follow-up, 9 patients required intensive care and 5 patients underwent neurosurgical surgery. The most common trauma etiology was falling from one's own level with 53.7%. The most common tomography pathology was non-displaced fracture. According to the evaluations made in accordance with the PECARN algorithm, CT was recommended in 18 cases (16.7%); CT was not recommended for 32 cases. Conclusions: The clinician's goal is to quickly and accurately diagnose clinically significant TBI while avoiding unnecessary CT imaging to protect against the adverse effects of radiation. We recommend using the PECARN algorithm for this purpose.
