Therapeutic Evaluation of Tumor Necrosis Factor-alpha Antagonist Etanercept against Traumatic Brain Injury in Rats: Ultrastructural, Pathological, and Biochemical Analyses.

PURPOSE: The aim of the present study was to investigate the effect of etanercept (ETA) on histopathological and biochemical changes after traumatic brain injury (TBI) in rats. MATERIALS AND METHODS: Thirty-six male Wistar albino rats were distributed into three groups (n = 12 each). Control group rats were not subjected to trauma. Trauma group rats were subjected to TBI only. ETA group rats were subjected to TBI plus ETA (5 mg/kg intraperitoneal [i.p.]). The groups were further subdivided into those sacrificed in the hyperacute stage (1 h after TBI) (control-1, trauma-1, and ETA-1 groups) and the acute stage (6 h after TBI) (control-6, trauma-6, and ETA-6 groups). Tissue levels of tumour necrosis factor-alpha, interleukin-1 beta, malondialdehyde, catalase, glutathione peroxidase, and superoxide dismutase were analyzed. Histopathological and ultrastructural evaluations were also performed. RESULTS: i.p. administration of ETA at 1 and 6 h significantly reduced inflammatory cytokine expression, attenuated oxidative stress and lipid peroxidation, prevented apoptosis, and increased antioxidant defense mechanism activity in comparison to trauma group. Histopathological and ultrastructural abnormalities were significantly reduced in ETA-treated rats compared to closed head injury trauma groups. CONCLUSIONS: ETA significantly improves neural function and prevents post-TBI histopathological damage in rats.

Thyroid Carcinoma Presenting as a Dural and Calvarial Metastasis Mimicking a Lipoma With Difficult Diagnosis of the Primary Lesion.

Calvarial and dural metastases of papillary thyroid carcinomas (PTC) are rarely reported in the medical literature. Most frequent calvarial metastases are seen to originate from lung, breast, and prostate cancers. Thyroid cancer metastases are generally well vascularized and cause destruction in the bone tissues. First choice of treatment in distant metastases of PTC is surgery and radioactive iodine treatment for the primary cause. Postsurgical radiotherapy is used in accepted and suitable patients.

Stereologic and ultrastructural comparison of human and rat amniotic membrane wrapping for rat sciatic nerve repair.

In this study we aimed to examine the effects on wound healing and nerve regeneration of human and rat amniotic membrane wraps around primary epineural anastomosis areas after a peripheral nerve transection injury in rats. We randomized 25 male adult rats with induced peripheral transection injuries into 5 groups (control, transection injury, primary epineural anastomosis [PEA] after injury, PEA with a human amniotic membrane [hAM] wrap, and PEA with a rat amniotic membrane [rAM] wrap groups and treated their injuries accordingly. We took tissue samples from the anastomosis regions, 12 weeks after the experiment, and analyzed them stereologically and ultrastructurally. We performed a statistical analysis with the recovered stereological counts and the measurement data. Our results showed that the use of amniotic membranes for allografts (between same species) instead of xenografts (between different species), along with microsurgery, provides a suitable microenvironment during the healing process with less immunological reaction on the injured site and supports axonal regeneration.

Etanercept Prevents Histopathological Damage after Spinal Cord Injury in Rats.

BACKGROUND: The aim of our study is to assess the neuroprotective effects of the tumor necrosis factor alpha (TNF-α) inhibitor etanercept (ETA) on histopathological and biochemical changes following spinal cord injury (SCI). PATIENTS AND METHODS: Fifty-four male Wistar albino rats were randomly assigned into three main groups: The sham, trauma, and ETA group (n = 18 per group). Each of these groups was further divided into three subgroups (n = 6 per subgroup) based on the different tissue sampling times postinjury: 1 h, 6 h, and 24 h. Clip compression model was used for SCI. Rats in the ETA group were treated with 5 mg/kg of ETA immediately after the clip was removed. After 1, 6, and 24 h, the spinal cord was totally removed between the levels T8-T10. Sample tissue was immediately harvested and fixed for histopathological and electron microscopic examination and were analyzed for TNF-α, interleukin-1ß (IL-1ß), superoxide dismutase (SOD), adenosine deaminase, catalase (CAT), and malondialdehyde levels in both the tissue and serum. RESULTS: The serum and tissue levels of cytokines and enzymes were seen to change after SCI between hyperacute, acute, and subacute stages. Treatment with ETA selectively inhibited TNF-α, and IL-1ß expression together with increased levels of antioxidative enzymes (SOD, CAT). CONCLUSION: Early administration of ETA after SCI may remarkably attenuate neuronal injury by decreasing tissue and serum TNF-α and IL-1ß levels, while increasing antioxidative enzymes such as SOD and CAT in subacute and acute stages, respectively.

Comparative evaluation of the electrophysiological, functional and ultrastructural effects of alpha lipoic acid and cyanocobalamin administration in a rat model of sciatic nerve injury.

BACKGROUND: Vitamin B12 and alpha lipoic acid (ALA) are known to promote functional and morphological recovery after peripheral nerve injury. OBJECTIVE: To compare the regenerative and neuroprotective effects of vitamin B12 and ALA treatment after sciatic nerve injury. METHODS: A total of 40 rats were randomly assigned to control (sciatic nerve exposure without injury or anastomosis), sham (sciatic nerve injury and epineural anastomosis were performed but no treatment was administered), PS (isotonic saline was administered for 12 weeks after surgery), ALA (2 mg/kg ALA was administered for 12 weeks after surgery), and vitamin B12 groups (2 mg/kg cyanocobalamin was administered for 12 weeks after surgery). Functional recovery was determined by footprint analysis, in vivo neurophysiology, and ex vivo histopathological examination. RESULTS: ALA treatment produced significant improvements in sciatic functional index values and non-significant improvements on electroneuromyography compared to vitamin B12 treatment. Upon histopathological examination, the regenerative effects of ALA were relevant to axonal structural recovery whereas vitamin B12 produced greater improvements in edema and myelination. CONCLUSIONS: While both vitamin B12 and ALA produced improvements after sciatic nerve injury, ALA was more functionally effective. The unique ultrastructural effects of vitamin B12 and ALA treatment should be considered in future studies.

A very rare spinal cord tumor primary spinal oligodendroglioma: A review of sixty cases in the literature.

LITERATURE REVIEW: In this study, we evaluated a case of primary spinal oligodendroglioma (PSO) with a rare localization between L3 and S2, and also examined sixty cases in the literature in terms of demographic characteristics, clinical, radiological, and histopathological characteristics, and treatment planning. A case of PSO has been presented, and the relevant literature between 1931 and 2016 was reviewed. A total of 57 papers regarding PSO were found and utilized in this review. The main treatment options include radical surgical excision with neuromonitoring, followed by radiotherapy. Despite these treatment protocols, the relapse rate is high, and treatment does not significantly prolong survival. Oligodendrogliomas are rare among the primary spinal cord tumors. Oligodendrogliomas are predominantly found in the cervical spinal cord, thoracic spinal cord, or junctions during childhood and adulthood. Extension to the sacral region, inferior to the Conus, is very rare. Furthermore, of the sixty cases in the literature, the case we present here is the first to be reported in this particular age group. These localizations usually occur in the pediatric age group and after relapses. While for a limited number of cases the oligodendroglioma initiates in the thoracic region and reaches as far as L2, we encountered a case of an oligodendroglioma within the range of L3 to S2. Clinical findings are observed in accordance with location, and magnetic resonance imaging is the gold standard for diagnosis.

Intradural Intramedullary Cervicothoracic Tumor With Long-Segmental Localization: A Case Report With Step-by-Step Surgical Treatment Strategy With Neuromonitorization.

Ependymomas are the most common gliomas of the conus and lower cord, with the cervical cord being the second most common location. These tumors can extend upward 3-4 vertebra, and some ependymomas can extend up over 15 segments. Depending on many factors, such as tumor size, lateralization, kyphotic deformity, and lordosis state, there are several posterior surgical options, including laminectomy, laminectomy and lateral mass screw-plate, and laminoplasty. In this study, we discuss a case of intradural intramedullary cervicothoracic ependymoma with long-segmental localization, as well as the general surgical principles of its excision with step-by-step demonstrative figures.

The Surgical Outcome of Traumatic Extraaxial Hematomas Causing Brain Herniation.

AIM: The aim of this study was to assess the surgical outcome and the prognostic importance of clinical and radiological data of patients operated emergently for an extraaxial hematoma causing brain herniation. MATERIAL AND METHODS: This retrospective study comprised 108 adult patients who were operated due to herniated traumatic extraaxial hematomas from January 2000 to January 2013. RESULTS: Of 108 patients, 63 patients (58.3%) were diagnosed as subdural hematoma (SDH), and 45 patients (41.7%) as epidural hematoma (EDH). An unfavorable outcome was significantly increased for patients who were diagnosed as SDH (90.4%) compared with EDH patients (33.3%). Mortality rate for herniated SDH patients was 65.1%, and 26.6% for herniated EDH patients. High mortality and unfavorable outcome ratios were associated with Glasgow Coma Scale scores at admission, mean postoperative intracranial pressure (ICP) values, type of the brain herniation, interval from the time of trauma to the time of hematoma decompression, the duration of the brain herniation, intraoperative acute brain swelling, hematoma volume and thickness, degree of the midline shift and the obliteration of the basal cisterns. CONCLUSION: Our data showed that, postoperative ICP values were one most important predictor of the mortality. We recommended postoperative ICP monitoring for all patients presenting with the brain herniation due to traumatic extraaxial hematoma.

Histomorphometric and Ultrastructural Evaluation of Long-Term Alpha Lipoic Acid and Vitamin B12 Use After Experimental Sciatic Nerve Injury in Rats.

AIM: To analyze the therapeutic effects of long-term alpha lipoic acid (A-LA) and vitamin B12 use via histomorphometric methods and electron microscopy in the transected sciatic nerves of rats. MATERIAL AND METHODS: Forty rats were randomized into five groups (n=8/group). In group I, 1 cm segment of sciatic nerve was resected without any other intervention. In group II (sham), following right sciatic nerve transection, primary epineurial anastomosis was performed by placing the edges of the nerve end-to-end. In group III (saline), after right sciatic nerve transection, the ends of the nerves were brought together and closed after application of intraperitoneal physiologic saline. In group IV, 2 mg/kg of alpha lipoic acid and in group V, 2 mg/kg of vitamin B12 was administered intraperitoneally before surgical intervention. RESULTS: Histomorphometric and electron microscopic analyses revealed that vitamin B12 did not prevent structural changes, abnormal myelination and g-ratio deviations regarding the functional aspects of the sciatic nerve. Alpha lipoic acid was more effective in restructuring the histomorphometric and structural aspects of the nerve with more myelinated fibers with optimal values (0.55-0.68) than vitamin B12 groups, in which the number of myelinated nerve fibers significantly decreased at optimal intervals (0.55-0.68). CONCLUSION: A-LA administration following peripheral nerve transection injury is more effective in promoting nerve healing regarding the structural aspects of the sciatic nerve compared to vitamin B12 and also myelination of nerve fibers by increasing g-values.

Esophageal perforation after anterior cervical surgery: a review of the literature for over half a century with a demonstrative case and a proposed novel algorithm.

PURPOSE: To review relevant data for the management of esophageal perforation after anterior cervical surgery. METHODS: A case of delayed esophageal perforation after anterior cervical surgery has been presented and the relevant literature between 1958 and 2014 was reviewed. A total of 57 papers regarding esophageal perforation following anterior cervical surgery were found and utilized in this review. RESULTS: The treatment options for esophageal perforation after anterior cervical surgery were discussed and a novel management algorithm was proposed. CONCLUSION: Following anterior cervical surgery, patients should be closely followed up in the postoperative period for risk of esophageal perforation. Development of symptoms like dysphagia, pneumonia, fever, odynophagia, hoarseness, weight loss, and breathing difficulty in patients with a history of previous anterior cervical surgery should alert us for a possible esophageal injury. Review of the literature revealed that conservative treatment is advocated for early and small esophageal perforations. Surgical treatment may be considered for large esophageal defects.

Management of Sacral Tumors Requiring Spino-Pelvic Reconstruction with Different Histopathologic Diagnosis: Evaluation with Four Cases.

In this retrospective study, surgical results of four patients with sacral tumors having disparate pathologic diagnoses, who were treated with partial or total sacrectomy and lumbopelvic stabilization were abstracted. Two patients were treated with partial sacral resection and two patients were treated with total sacrectomy and spinopelvic fixation. Fixation methods included spinopelvic fixation with rods and screws in two cases, reconstruction plate in one case, and fresh frozen allografts in two cases. Fibular allografts used for reconstruction accelerated bony union and enhanced the stability in two cases. Addition of polymethyl methacrylate in the cavity in the case of a giant cell tumor had a positive stabilizing effect on fixation. As a result, we can conclude that mechanical instability after sacral resection can be stabilized securely with lumbopelvic fixation and polymethyl methacrylate application or addition of fresh frozen allografts between the rods can augment the stability of the reconstruction.

Antioxidant and antiapoptotic effects of darbepoetin-α against traumatic brain injury in rats.

INTRODUCTION: In this study, we tried to determine whether darbepoetin-α would protect the brain from oxidative stress and apoptosis in a rat traumatic brain injury model. MATERIAL AND METHODS: The animals were randomized into four groups; group 1 (sham), group 2 (trauma), group 3 (darbepoetin α), group 4 (methylprednisolone). In the sham group only the skin incision was performed. In all the other groups, a moderate traumatic brain injury modelwas applied. RESULTS: Following trauma both glutathione peroxidase, superoxide dismutase levels decreased (p < 0.001 for both); darbepoetin-α increased the activity of both antioxidant enzymes (p = 0.001 and p < 0.001 respectively). Trauma caused significant elevation in the nitric oxide synthetase and xanthine oxidase levels (p < 0.001 for both). Administration of darbepoetin-α significantly decreased the levels of nitric oxide synthetase and xanthine oxidase (p < 0.001 for both). Also, trauma caused significant elevation in the nitric oxide levels (p < 0.001); darbepoetin-α administration caused statistically significant reduction in the nitric oxide levels (p < 0.001). On the other hand, malondialdehyde levels were increased following trauma (p < 0.001), and darbepoetin α significantly reduced the malondialdehyde levels (p < 0.001). Due to the elevated apoptotic activity following the injury, caspase-3 activity increased significantly. Darbepoetin-α treatment significantly inhibited apoptosis by lowering the caspase-3 activity (p < 0.001). In the darbepoetin group, histopathological score was lower than the trauma group (p = 0.016). CONCLUSIONS: In this study, darbepoetin-α was shown to be at least as effective as methylprednisolone in protecting brain from oxidative stress, lipid peroxidation and apoptosis.

Potential neuroprotective effect of Anakinra in spinal cord injury in an in vivo experimental animal model.

OBJECTIVE: To evaluate the therapeutic effects of inhibiting interleukin-1 beta (IL-1 beta) in vivo using Anakinra in an experimental model of spinal cord injury (SCI). METHODS: All experimental procedures were performed in the animal laboratory of Ankara Education and Research Hospital, Ankara, Turkey between August 2012 and May 2014. The SCI was induced by applying vascular clips to the dura via a 4-level T5-T8 laminectomy. Fifty-four rats were randomized into the following groups: controls (n = 18), SCI + saline (n = 18), and SCI + Anakinra (n = 18). Spinal cord samples were obtained from animals in both SCI groups at one, 6, and 24 hours after surgery (n = 6 for each time point). Spinal cord tissue and serum were extracted, and the levels of IL-1 beta, malondialdehyde, glutathione peroxidase, superoxide dismutase, and catalase were analyzed. Furthermore, histopathological evaluation of the tissues was performed. RESULTS: The SCI in rats caused severe injury characterized by edema, neutrophil infiltration, and cytokine production followed by recruitment of other inflammatory cells, lipid peroxidation, and increased oxidative stress. After SCI, tissue and serum IL-1 beta levels were significantly increased, but were significantly decreased by Anakinra administration. Following trauma, glutathione peroxidase, superoxide dismutase, and catalase levels were decreased; however, Anakinra increased the activity of these antioxidant enzymes. Malondialdehyde levels were increased after trauma, but were unaffected by Anakinra. Histopathological analysis showed that Anakinra effectively protected the spinal cord tissue from injury. CONCLUSION: Treatment with Anakinra reduces inflammation and other tissue injury events associated with SCI.

Therapeutic evaluation of interleukin 1-beta antagonist Anakinra against traumatic brain injury in rats.

BACKGROUND: The aim of this study was to evaluate the therapeutic efficiency of Anakinra, an IL-1ß antagonist with anti-inflammatory effects, in an experimental model of traumatic brain injury (TBI). METHODS: Fifty-four rats underwent TBI after a weighted object was dropped onto a metal disc secured to their skulls. Animals were randomized into 3 main groups: control (n=18), TBI + saline (n=18; six animals per time-point) with samples obtained at the first, sixth and twenty-fourth h postoperatively, and TBI + Anakinra (n=18; six animals per time-point) with brain samples obtained at the first, sixth and twenty-fourth h postoperatively. Brain tissue and blood serum were extracted for the analysis of IL-1ß, malondialdehyde, glutathione peroxidase, superoxide dismutase, and catalase levels. Tissue sections were evaluated histopathologically under a light microscope. RESULTS: After trauma, tissue and serum IL-1ß levels were significantly elevated and after Anakinra administration, these levels substantially decreased. Glutathione peroxidase, superoxide dismutase, and catalase activity decreased following TBI and Anakinra administration proved effective in increasing the activity of these antioxidant enzymes. Histopathological analysis confirmed that Anakinra might protect the brain tissue and nerve cells from injury. CONCLUSION: Results demonstrate that Anakinra reduces the development of inflammation and tissue injury events associated with TBI.

The histopathological and ultrastructural effects of the topical application of bacitracin on the cerebral cortex in rats.

AIM: Bacitracin is one of the most frequently used agents for the topical irrigation of the cerebral cortex. The aim of this study is to investigate whether bacitracin has histopathological and ultrastructural effects when applied topically to the cerebral cortex. MATERIAL AND METHODS: Twenty-eight rats were randomly assigned to four groups. Except the control group, each rat underwent left frontoparietal craniectomy with dural removal. Then, in the sham group a piece of dry absorbable gelatin sponge was placed over the left hemisphere; in the saline group a gelatin sponge soaked in normal saline; and in the bacitracin group a gelatin sponge soaked in 500 units bacitracin was used. After 48 hours, brain tissues were extracted for histopathological and electron microscopic analyses. RESULTS: Among the four groups dark stained neurons were found to be statistically higher in number in the bacitracin group compared with the control, sham and saline groups. Electron microscopic evaluation revealed that, in the bacitracin group, almost all cytoplasmic organelles were poorly preserved. CONCLUSION: Topical application of the bacitracin on to the cerebral cortex caused histopathological and ultrastructural changes in the neural tissue. These changes may be an evidence for the neurotoxic effects of bacitracin.

Management and retrospective analysis of primary and metastatic sacral tumors and infections: evaluation with 73 cases.

OBJECTIVES: This study aims to evaluate the clinicopathologic characteristics and treatment modalities of 73 patients with benign and malign sacral tumors and infections from a single institution. PATIENTS AND METHODS: Seventy-three patients (42 males, 31 females; mean age 48.9 years), who were treated between July 1991 and December 2013, with benign, malign tumors, and infections of the sacrum were retrospectively analyzed for a mean follow-up period of 25.4 months, and a review of the literature was conducted. While 36 patients were treated surgically, 37 were treated medically. Fifty-four patients were diagnosed with malign, and 19 with benign or infectious tumors. RESULTS: In 54 patients with malign tumors, metastasis was the most common diagnosis in 20 patients followed by chordoma in 11, and multiple myeloma in 10 patients. Common benign lesions were osteomyelitis in four patients, and giant cell tumor and schwannoma in three patients each. Local recurrence was most commonly observed in the chordoma and chondrosarcoma groups with a rate of 50%. Seven patients including five with metastatic disease, one with chondrosarcoma, and one with chordoma died during follow-ups. While urinary and anal incontinence developed in seven patients after sacral resection, deep infection was reported in four, and superficial infection was reported in two patients. CONCLUSION: Because of the high complication rates in malign sacral tumors, we should perform wide resections with partial or total sacrectomy. Chordoma and chondrosarcoma patients should be screened closely due to a possible recurrence risk after sacrectomy while preserving the nerve roots as possible. Aggressive curettage should be combined with adjuvant methods in benign lesions due to high recurrence rates in sacral localization.

Incidentally diagnosed giant invasive sacral schwannoma. Its clinical features and surgical management without stability.

Schwannomas are benign encapsulated tumors of Schwan cells that grow slowly along the peripheral myelin nerve fibers. Sacral spinal schwannomas are very rare, and the incidence of sacral schwannoma ranges from 1-5% of all spinal schwannomas, and only around 50 cases are reported in the literature. There are 3 defined types of sacral schwannomas. These are retroperitoneal or presacral, intra osseous, and spinal schwannomas. Patients commonly present with complaints of pain and paresthesia due to the spinal schwannoma extending to extra spinal tissues. Direct x-ray, CT, MRI, and scintigraphy are used for preoperative diagnosis and treatment planning. Local recurrence and transformation to malignancy is very rare. For this reason, the frequently preferred treatments are subtotal removal of the mass or simple enucleation. In our article, we discuss the clinical features and the surgical treatment we performed without the need for stabilization in an incidentally determined giant invasive schwannoma case.

Painful scoliosis due to superposed giant cell bone tumor and aneurysmal bone cyst in a child.

Giant cell bone tumors are the most common precursor lesions of aneurysmal bone cysts (ABCs) developing secondarily. In giant cell bone tumors containing an explicit ABC component, the observation of the solid component of the giant cell bone tumor plays a critical role in the separation of the primary ABC. In general, ABC cases together with giant cell tumors in the bone are diagnosed histopathologically. The combination of giant cell bone tumor with superposed ABC and that of painful scoliosis with backache is rarely seen in children. In this case study, we discussed the diagnosis and the treatment of a giant cell tumor and superposed an ABC present in the fifth lumbar spine in a pediatric patient admitted to our clinic with a complaint of acute scoliotic back pain.

Giant intradiploic epidermoid cyst presenting as solitary skull mass with intracranial extension.

Epidermoid cysts are rare benign tumors that constitute 0.3% to 1.8% of all intracranial tumors. They are inclusion tumors that include epidermoid elements and are most commonly located in the cerebellopontine angle cistern and the parasellar region, and their location in the diploic space is very rare. These lesions slowly grow and usually do not involve the intracranial compartment. In this article, a case of giant epidermoid cyst located in the left frontal intradiploic space is presented with clinical, radiologic features and surgical treatment.

Unusual traumatic midthoracic spondyloptosis and its surgical management: case report.

Posttraumatic spondyloptosis develops as a result of complete subluxation of the vertebral bodies and causes complete transection of the spinal cord. Severe trauma-related spondyloptosis of the upper-mid thoracic region is a rare form of spinal trauma. Traumatic midthoracic spondyloptosis is quite rare, and radiology plays an important role in the diagnosis and treatment of this condition. Surgical reconstruction and stabilization are required for early mobilization and rehabilitation of patients with this injury. Here, we report the clinical features, radiographic findings, and management of an unusual case of traumatic midthoracic spondyloptosis that showed complete spinal cord transection and was operated.