Investigation of the effects of tramadol and levetiracetam in prevention of peridural fibrosis after laminectomy in rats

Amaç: Ameliyat sonrası geç dönemde oluşan peridural fibrosiz dokusu nöral oluşumların ve sinir köklerinin etrafını sarıp radiküler semptomlara ve bu semptomlara yönelik yeniden o bölgeye cerrahi girişim uygulama zorunluluğuna neden olabilir. Peridural skar dokusu yeniden ameliyat yapılması zorunluluğu ortaya çıktığında dura ve sinir kökü yaralanması gibi komplikasyonların riskini artırır. Peridural fibrozisi önleyebilmek veya düzeltebilmek için birçok ilaç ve yöntem denenmiş ancak etkinliği kabul edilmiş bir tedavi metodu henüz oluşturulamamıştır. Bu çalışmada tramadol hidroklorür ve levetirasetam isimli farmakolojik ajanların ratlarda oluşturulan peridural fibrozisi önlemeye yönelik etkileri araştırıldı. Metod: Çalışmada 32 tane 300-350 gr ağırlığında erkek Wistar albino rat şu şekilde gruplara ayrıldı: Sham grubu (cerrahi girişim uygulandı ve hiçbir farmakolojik ajan verilmedi, n=6+2); MP grubu (cerrahi girişim uygulandı ve 14 gün süreyle 10 mg/kg/gün metilprednizolon sodyum süksinat intraperitoneal verildi; n=6+2); TRA grubu (cerrahi girişim uygulandı ve 14 gün süreyle 0,6 mg/kg/gün tramadol hidroklorür intraperitoneal verildi; n=6+2); LEV grubu (cerrahi girişim uygulandı ve 14 gün süreyle 15 mg/kg/gün levetirasetam intraperitoneal verildi; n=6+2). Sedasyon anestezi altında tüm deneklere torakal 9, 10 ve 11 standart laminektomi uygulandı ve ardından 14 gün süreyle ilaç tedavileri uygulandı. Cerrahi işlemden 4 hafta sonra tüm hayvanlara ötenazi uygulanıp omurgaları blok şekilde çıkarılıp laminektomi alanının ortasından geçecek şekilde ikiye bölündü. Proksimal parça histopatolojik incelemeler ve distal parça biyokimyasal incelemeler için saklandı. Bulgular: Histopatolojik preparatlarda hemotoksilen eozin boyama kullanılarak peridural fibrozisin yoğunluğu ve Masson-Trikrom boyama kullanılarak oluşan kollajenin yoğunluğu derecelendirildi. İmmünohistokimyasal preparatlarda COL1A1 ve ACTA2 boyama yapılarak kollajen ve ?-SMA yoğunlukları derecelendirildi. ELISA yöntemi kullanılarak TNF-?, IL-6, TGF-ß, CTGF, kaspaz 3, GSH/GSSG düzeyleri saptandı. Western blot tekniği kullanılarak pAMPK, mTOR, pmTOR ve pmTOR/mTOR düzeyleri ölçüldü. Histopatolojik incelemelerde peridural fibrozis düzeyinin en fazla Sham ve LEV grubunda oluştuğu; TRA ve MP gruplarında ise daha düşük düzeyde oluduğu saptandı. Masson-Trikrom boyamada Sham ve LEV gruplarındaki kollajen yoğunluk derecelerinin MP ve TRA gruplarına göre fazla olduğu görüldü. İmmunhistokimyasal boyama sonrası Sham ve LEV gruplarında ölçülen COL1A1 H-SCORE değerlerinin MP ve TRA gruplarından daha yüksek olduğu saptandı. ACTA2 için H-SCORE değerlerinin gruplar arasında farklı olmadığı saptandı. Biyokimyasal incelemelerde TNF-?, IL-6, GSH/GSSH, kaspaz-3, TGF1? ve CTGF düzeylerinin Sham-MP, Sham-ELP, Sham-OXT, MP-ELP, MP-OXT ve ELP-OXT grupları arasında farklı olduğu görüldü. Western blot analizleri sonunda p-AMPK değerlerinin Sham-MP, Sham-TRA ve Sham-LEV grupları arasında farklı olduğu görüldü. pmTOR ve pmTOR/ mTOR değerlerinin Sham-MP, Sham-TRA, Sham-LEV, MP-TRA ve MP-LEV grupları arasında farklı olduğu saptandı. mTOR değerlerinin Sham-MP, Sham-TRA, Sham-LEV ve TRA-LEV grupları arasında farklı olduğu bulundu. Histopatolojik ve immünhistokimyasal incelemeler sonunda metilprednizolon ve tramadolun peridural fibrozis derecelerini, kollajen yoğunluk düzeylerini ve kollajen oluşumunu azaltabildikleri saptandı. Her üç ajanın da TNF, IL-6, kaspaz-3, TGF? ve CTGF düzeylerini azaltarak peridural fibrozisi azaltmada antienflamatuar ve antiapopitotik etkinliklerinin olduğu görüldü. Her üç ajanın da GSH/ GSSG düzeylerini arttırarak antioksidan etkinlik gösterdiği saptandı. Her üç ajanın da pAMPK değerlerini artırarak, pmTOR düzeylerini azaltarak otofajiyi ve buna bağlı dokunun rejenerasyonunu artırdığı ve böylece peridural fibrozisi azalttıkları bulundu. Sonuç: Sonuç olarak her üç ajanın da antienflamatuar, antioksidan, antiapopitoitk ve güçlü otofaji ilişkili doku rejenerasyonu etkilerinin olduğu ve bu etkileri sayesinde ratlarda uygulanan laminektomi modelinde oluşan peridural fibrozisi azaltabildikleri bulundu. Anahtar kelimeler: Peridural, Epidural, Fibrozis, Post-laminektomi, Postoperatif, Spinal, Adezyon, Nöroşirurji, Laminektomi, Dura, Bariyer Destekleyen Kurumlar: Kırıkkale Üniversitesi Bilimsel Araştırma Proje (BAP) Koordinasyon Birimi (BAP Numarası: 2021/ 004)Purpose: Peridural fibrosis tissue, which occurs in the late postoperative period, may cover the neural tissues and nerve roots and cause radicular symptoms and the necessity of applying surgical intervention to that area for these symptoms. Peridural scar tissue increases the risk of complications such as dural and nerve root injury when reoperation is required. Many drugs and methods have been tried to prevent or reduce peridural fibrosis, but a treatment method whose effectiveness has been accepted has not been established yet. This study investigated the effects of tramadol hydrochloride and levetiracetam on preventing peridural fibrosis in rats. Method: In this study, 32 male Wistar albino rats weighing 300-350 g were divided into groups as follows: Sham group (surgical intervention was performed but no pharmacological agent was administered, n=6+2); MP group (surgical intervention was performed and 10 mg/kg/day methylprednisolone sodium succinate was administered intraperitoneally for 14 days; n=6+2); TRA group (surgical intervention was performed and 0.6 mg/kg/day tramadol hydrochloride was administered intraperitoneally for 14 days; n=6+2); and LEV group (surgical intervention was performed and 15 mg/kg/day levetiracetam was administered intraperitoneally for 14 days; n=6+2). Thoracic 9, 10, and 11 standard laminectomies were performed on all subjects under sedation anesthesia, followed by drug treatments for 14 days. Four weeks after the surgical intervention, all animals were euthanized and their spinal columns removed as a block, divided into two parts passing through the middle of the laminectomy area. The proximal part was used for histopathological evaluations and the distal part for biochemical investigations. Results: In histopathological specimens, the intensity of peridural fibrosis was graded using hematoxylin-eosin staining and the density of collagen was graded using Masson-Trichrome staining. In immunohistochemical specimens, collagen and alpha-SMA densities were graded by staining with COL1A1 and ACTA2, respectively. TNF-?, IL-6, TGF-ß, CTGF, caspase-3, and GSH/GSSG levels were determined using the ELISA method. The levels of pAMPK, mTOR, pmTOR, and mTOR/p-mTOR were measured using the western blot. Histopathological and immunohistochemical evaluations revealed that methylprednisolone and tramadol were able to reduce the degree of peridural fibrosis, collagen density levels, and collagen formation. All three agents showed anti-inflammatory and antiapoptotic properties in reducing peridural fibrosis by decreasing TNF, IL-6, caspase-3, TGF?, and CTGF levels. Additionally, they also showed antioxidant activity by increasing GSH/GSSG levels. Finally, they maintained autophagy and related tissue regeneration in reducing peridural fibrosis by increasing pAMPK values and decreasing pmTOR levels. Conclusion: In conclusion, it was concluded that all three agents have anti-inflammatory, antioxidant, anti-apoptotic, and autophagy-related tissue regeneration properties, and thanks to these effects, they can reduce peridural fibrosis in the laminectomy model in rats. Keywords: Peridural, Epidural, Fibrosis, Post-laminectomy, Postoperative, Spinal, Adhesion, Neurosurgery, Laminectomy, Dura, Barrier Supporting Institutions: Kırıkkale University Scientific Research Project (BAP) Coordination Unit (BAP Number: 2021/ 004

Can routine biochemical tests be a short-term prognostic biomarker in patients operated for chronic subdural hematoma?

Objectives: The effect of routine blood biochemistry parameters on the short-term prognosis of patients with chronic subdural hematoma (CSDH) has not been evaluated in literature before. In this study, it was aimed to establish markers for determination of short-term prognosis using data of patients who were operated for CSDH. Methods: During admission to hospital, data of patients including age, sex, antiaggregan and/or anticoagulant drugs usage, comorbidity, Glasgow Coma Scale (GCS) and Glasgow Outcome Scale scores were evaluated. Location and thickness of CSDH were recorded using brain CT or MR images. Blood leukocyte, neutrophil, lymphocyte, eosinophil, basophil, platelet count results, neutrophil-lymphocyte ratio and platelet-lymphocyte ratio results, activated prothrombin time and INR values, serum glucose, aspartate aminotransferase, alanine aminotransferase, C-reactive protein, sodium, potassium, blood urea nitrogen and creatinine level values were also recorded. Patients were divided into two groups according to CSDH located “unilaterally (n=19)” and “bilaterally (n=12)”. In addition, patients with unilateral CSDH were divided into two groups as CSDH located at the "right hemisphere (n=6)” and "left hemisphere (n=13)". Results: It was concluded that short-term prognosis of patients with unilateral or bilateral CSDH was similar. Correlation analysis showed no correlation between short-term prognosis and demographic, clinical and laboratory findings. However, Likelihood Ratio test revealed that GCS score could be a biomarker in order to predict short-term prognosis of these patients, albeit weak (X2=6.138, p=0.046). Conclusion: It was thought that GCS scores could be effective in predicting short-term prognosis in patients with CSDH but routine biochemistry laboratory parameters could not predict short-term prognosis of these patients

Analysis of biochemical laboratory values to determine etiology and prognosis in patients with subarachnoid hemorrhage: a clinical study

KISA, Ucler/0000-0002-8131-6810; BAKAR, BULENT/0000-0002-6236-7647WOS: 000459561000008PubMed: 30417744Objectives: The aim of this study was to establish prognostic and predictive markers in patients with subarachnoid hemorrhage (SAH) using simple laboratory methods. Methods: A retrospective examination was made of patients with SAH diagnosed secondary to isolated head trauma, isolated anterior communicating artery aneurysm rupture, and angiography-negative SAH. Age, gender, Glasgow Coma Scale (GCS) scores, and Fisher's grade scores, Glasgow Outcome Scale (GOS) scores, leukocyte count, neutrophil count, lymphocyte count, platelet count, neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio results (PLR) were evaluated. Results: NLR and PLR values, which were similar in patients with spontaneous SAH, were significantly high in patients with traumatic SAH. NLR and PLR values could be 80% sensitive and 75% specific for distinguishing traumatic SAH from spontaneous SAH. Eosinophil count was lower in patients with angiography-negative SAH and patients with aneurysmal SAH than in patients with traumatic SAH. Initially measured GCS score, Fisher's grade score, eosinophil, neutrophil and lymphocyte counts could be prognostic in all patients with SAH. Moreover, it was concluded that the initially measured number of eosinophils might be directly related to patient prognosis. The eosinophil count was generally found to be high in traumatic SAM patients and it was observed that this parameter could be predictive for these patients. Lymphocyte count and NLR values could be prognostic markers in patients with angiography-negative SAH. Conclusion: NLR, PLR and eosinophil count values could be predictive for etiological factors (traumatic SAH or spontaneous SAH) of patients who were admitted unconscious to the emergency room with SAH detected on radiological imaging

Analysis of radiological measurement parameters that can predict the type of treatment to be applied in odontoid fractures: Clinical research

Introduction: Although various conservative and surgical treatment methods have been proposed, treatment options for patients with odontoid fractures remain controversial. This study was conducted to determine some demographic and radiological measurement parameters that can predict treatment options in patients with odontoid fractures. Materials and Methods: The patients were separated into the surgery (−) group (n = 9) and the surgery (+) group (n = 10). Patient data were recorded of age, gender, type of odontoid fracture, morphological measurement results obtained from computed tomography images, treatment regimens, duration of stay in the hospital, and mortality rate. In the operating room, a halo-vest corset or Philadelphia-type cervical collar was applied to the surgery (−) patients after the reduction of the fracture under fluoroscopy. Anterior odontoid lag screw fixation was performed on surgery (+) patients. Results: The amount of displacement of the fractured odontoid, the distance between the C1 vertebra and the odontoid process, the angle between the posterior wall of the odontoid process and the posterior wall of the clivus, the slip angle, and the anterior to posterior width of the spinal canal were not different between the groups. No difference was determined between the groups in respect of the amount of lateral displacement of the odontoid process in the spinal canal in the axial plane and the angle of the fractured odontoid process with the C2 vertebral body. Conclusion: This preliminary study showed that the demographic data and radiological measurement parameters analyzed in the present study could not be used as predictive markers either in decision-making for treatment modality or mortality risk