Thioredoxin System and miR-21, miR-23a/b and let-7a as Potential Biomarkers for Brain Tumor Progression: Preliminary Case Data.

BACKGROUND: The thioredoxin system and microRNAs (miRNAs) are potential targets for both cancer progression and treatment. However, the role of miRNAs and their relation with the expression profile of thioredoxin system in brain tumor progression remains unclear. METHODS: In this study, we aimed to determine the expression profiles of redox components Trx-1, TrxR-1 and PRDX-1, and oncogenic miR-21, miR-23a/b and let-7a and oncosuppressor miR-125 in different brain tumor tissues and their association with increasing tumor grade. We studied Trx-1, TrxR-1, and PRDX-1 messenger RNA expression levels by quantitative real-time polymerase chain reaction and protein levels by Western blot and miR-23a, miR-23b, miR-125a, miR-21, and let-7a miRNA expression levels by quantitative real-time polymerase chain reaction in 16 glioma, 15 meningioma, 5 metastatic, and 2 benign tumor samples. We also examined Trx-1, TrxR-1, and PRDX-1 protein levels in serum samples of 36 patients with brain tumor and 37 healthy volunteers by enzyme-linked immunosorbent assay. RESULTS: We found that Trx-1, TrxR-1, and PRDX-1 presented high messenger RNA expression but low protein expression in low-grade brain tumor tissues, whereas they showed higher protein expression in sera of patients with low-grade brain tumors. miR-23b, miR-21, miR-23a, and let-7a were highly expressed in low-grade brain tumor tissues and positively correlated with the increase in thioredoxin system activity. CONCLUSIONS: Our findings showed that Trx-1, TrxR-1, miR-21, miR-23a/b, and let-7a might be used for brain tumor diagnosis in the clinic. Further prospective studies including molecular pathway analyses are required to validate the miRNA/Trx system regulatory axis in brain tumor progression.

Neuroprotective effects of adrenomedullin in experimental traumatic brain injury model in rats.

BACKGROUND: Traumatic brain injuries cause damages in the brain in several ways, which include cell death because of edema, disruption of the blood-brain barrier, shear stress, and ischemia. In this study, we investigated the effects of adrenomedullin (AM) on oxidative stress and inflammation after head traumas in a rat model. METHODS: Eighteen male adult Wistar albino rats were randomized into three groups (n=6). No traumas were applied to the con-trol (C) group. Traumas were applied in line with Marmarau trauma model in the trauma group. The rats in the AM treatment group were treated with post-traumatic 12 µg/kg i.p. AM in addition to the trauma group. The rats were followed for 7 days in all groups and were then sacrificed. Brain tissues and blood samples were taken. RESULTS: In the trauma group, both tissue and serum MDA, TNF-α, and IL-6 levels were significantly increased compared to the control group (p<0.05). In the AM-treated group, serum TNF-α levels were significantly decreased compared to the trauma group (p<0.05). In the trauma group, both tissue and serum GSH levels were significantly decreased compared to the control group (p<0.05). In the trauma group, serum Vitamin D3 levels were significantly decreased compared to the control group (p<0.05). In the AM-treated group, both tissue and serum GSH levels were significantly increased compared to the trauma group (p<0.05). CONCLUSION: These results indicate that AM has neuroprotective effects on traumatic brain injury in a rat model.

Stereotactic Radiosurgery after Subtotal Resection of Critically-Located Grade I Meningioma: A Single-Center Experience and Review of Literature.

AIM: To analyze the results of stereotactic radiosurgery in 295 patients with residual Grade I meningiomas located at parasellar region, petroclival region, cerebellopontine angle and parasagittal region. MATERIAL AND METHODS: A total of 295 patients with Grade 1 residual Meningiomas (197 women, 98 men), who were treated by adjuvant radiosurgery in Gazi University Gamma Knife Center between 2004-2015 were analyzed. WHO Grade 2 and 3 meningiomas were not included in our study. Minimum radiological follow-up was 24 months. The median follow-up was 54 months. The tumor volume, location, treatment dose, morbidity, progression free survival and tumor control rate were analyzed. RESULTS: The median tumor volume was 5.2 cm3 (0.04-39.7), median age was 50 (20-80), median dose was 14 Gy and tumor control rate was 94.5% (stationary in 85.0%, volume reduction in 9.5%). Increase in tumor volume was seen in 16 patients (5.5%) and re-operation was performed in 5 of them (1.6%). Stereotactic radiosurgery was performed again for 8 patients (2.7%).The location of the tumors was as follows: 39.3% parasellar region, 20% cerebellopontine angle, 13.6% petroclival and 27.1% was parasagittal, falcine or convexity. Major morbidities were detected in 6 (2%) patients. Minor morbidities were detected in 18 (6.1%) patients. CONCLUSION: Stereotactic radiosurgery is an effective and safe treatment modality for residual Grade I meningiomas.

The Effects of Minocycline on the Hippocampus in Lithium- Pilocarpine Induced Status Epilepticus in Rat: Relations with Microglial/Astrocytic Activation and Serum S100B Level.

AIM: To investigate possible correlations between serum S100B levels and microglial/astrocytic activation in status epilepticus (SE) in lithium-pilocarpine-exposed rat hippocampi and whether serum S100B levels linearly reflect neuroinflammation. Additionally, to assess the effects of minocycline (M), an inhibitor of neuroinflammation. MATERIAL AND METHODS: Rats were divided into 4 groups (6/group), namely, control (C), sham, SE, and SE+M. Animals were exposed to lithium-pilocarpine to induce SE in the SE and SE+M groups. Cardiac blood was collected to measure S100B levels, and coronal brain sections including the hippocampus were prepared to examine microglial/astrocytic activation and to evaluate neuroinflammation at day 7 of SE. RESULTS: Serum S100B levels, OX42 (+) microglia in CA1, and GFAP (+) astrocytes in both CA1 and dentate gyrus (DG) were higher in the SE+M group than in the C group. Most importantly, highly positive correlations were found between S100B levels and microglial activation in CA1, apart from astrocytic activation in CA1 and DG. Unexpectedly, microglial activation in CA1 and astrocytic activation in DG were also enhanced in the SE+M group compared with the C group. Moreover, M administration reversed the neuronal loss observed in DG during SE. CONCLUSION: These results suggest that serum S100B is a candidate biomarker for monitoring neuroinflammation and that it may also help predict diagnosis and prognosis.

Turkish Board of Neurological Surgery.

AIM: To provide information on the process and the results of the Turkish Board of Neurological Surgery and increase the relevant awareness. MATERIAL AND METHODS: The number of applications to the written and oral board exams organized by the Turkish Neurosurgical Society Proficiency Board since 2006, the number of successful and unsuccessful participants, and the number of the neurosurgery residents and specialists who applied to the exam were evaluated. RESULTS: A total of 554 candidates took the exam since 2006 when the first TBNS was applied. Two hundred and sixty of the candidates were successful (46.9%), and 294 (53.1%) were unsuccessful. Two hundred and forty six (44.4%) of those who took the test were neurosurgeons, 308 (55.6%) were neurosurgery residents who had completed their 3rd year in their training. The highest score in the written exams was 93/100, and the lowest score was 33/100. In verbal exams, a total of 73 candidates participated, and 66 (90.4 %) of them were successful while 7 of them (9.6%) were unsuccessful. CONCLUSION: Board exams are inevitable to provide a certain level of education and standardization in the training of neurosurgery. Our duty as neurosurgeons is to participate in these exams and work to increase participation for continuing education.

Investigation of the Effect of Alemtuzumab in an Experimental Spinal Cord Trauma Model in Rats.

OBJECTIVE: Spinal cord injuries generate the most negative response to medical treatment among all general body injuries. This important morbidity is thought to be caused by a complex secondary damage mechanism. In the present study, we examined the neuroprotective effects of alemtuzumab in a spinal cord trauma model. METHODS: We divided 24 Long-Evans male rats into 4 groups (n = 6 per group). Laminectomy was performed at T5-T8 in all groups. Trauma was applied using the Yasargil temporary aneurysm clip for 60 seconds at these spinal cord levels in all groups, except for group 1. Next, 1 mg/kg of alemtuzumab was administered to each rat in groups 3 and 4. A functional evaluation was performed on days 1, 3, and 5 in groups 1, 2, and 4, and the rats were then sacrificed. The rats in group 3 were sacrificed on the third postoperative day to observe the early effects of alemtuzumab. The biochemical examination findings of malondialdehyde and glutathione in plasma and tissue samples and histopathological findings of the spinal cord were evaluated and compared by statistical analysis. RESULTS: The inflammatory findings in the trauma group were not seen in either group treated with alemtuzumab. The clinical motor examination and inclined plane test results were also significantly better in these groups. CONCLUSION: Our results have shown that alemtuzumab might prevent spinal cord injury after trauma and is a histopathologically and biochemically strong anti-inflammatory, antioxidant, and neuroprotective agent.

The effects of infusion of perineural pregabalin in the experimentally created sciatic nerve anastomosis in rats.

INTRODUCTION AND OBJECT: The aim of our study was to assess the effect of perineural pregabalin administration on the success of coaptation in experimental rat sciatic nerve anastomosis by measuring the expression of anti-inflammatory cytokine TGF-ß. It is thus to provide alternative solutions to this problem which we often see in clinical practice and whose results are not satisfactory. METHODS: In our study, 40 adult, male, Sprague-Dawley rats; 5 groups were randomly assigned. Group 1: This group's sciatic nerves were dissected and the surgical site was sutured. Group 2: Rats whose sciatic nerves are sectioned transversely through the full-thickness and end-to-end anastomosis is performed and no additional procedure is performed. Group 3: Intraperitoneal administration of 30 mg / kg pregabalin for 7 days with anastomosis. Group 4: 30 mg/kg pregabalin given orally for 7 days with anastomosis. Group 5: Given 10 microliters / h pregabalin subcutaneous perineural infusion for 7 days with anastomosis. After 60 days of surgery, the experiment was terminated with high dose thiopental (50 mg/kg). The right sciatic nerves of all animals were taken and sections obtained were examined immunohistopathologically. RESULTS: Inflammation was significantly less in the 5th group than in the other groups. TGF-ß expression in Groups 3, 4, and 5 is significantly higher than Groups 1 and 2, which also supports this situation. Although the expression in group 5 was not statistically significant, the number of TGF-ß expression was higher than Groups 3 and 4. In terms of immunohistochemical properties; 1 to 3, 1 to 4, 1 to 5, 2 to 5 groups were statistically significant (p <0,05). CONCLUSIONS: In conclusion, perinural infusion of pregabalin into the anastomotic region has not been previously tried in the literature and it has been found that immunohistochemistry provides positive contributions to healing of anastomosis. More research is needed to demonstrate that this effect is superior to other methods of administration of the drug. KEY WORDS: Anastomosis, Peripheral nerve, Perineural, Pregabalin, Sciatic nerve.

Effect of gabapentin on primary surgical treatment of experimental sciatic nerve injury in rats.

BACKGROUND: The aim of our study is to minimize the morbidity related to nerve injury by determining the protective effects of gabapentin in experimental sciatic nerve injury and end-to-end anastomosis model in rats and to guide clinical studies on this subject. METHODS: In our study, 40 adult male Sprague-Dawley rats were randomly divided into the following five groups: I: Only surgical intervention was applied; II: The sciatic nerve was cut properly and was repaired by end-to-end anastomosis. No additional procedure was performed; III: A single dose of gabapentin at 30 mg/kg was given after anastomosis; IV: 30 mg/kg gabapentin was given for 3 days after anastomosis; and V: 30 mg/kg gabapentin was given for 7 days after anastomosis. The experiment was terminated with high-dose thiopental (50 mg/kg) 60 days after the surgical intervention. The right sciatic nerve was taken from all animals. The obtained sections were examined immunohistopathologically. RESULTS: Immunohistochemical properties and Schwann cell proliferation were found to be statistically significantly lower in the control group than in the other groups. Schwann cell proliferation was higher in Group 3 than in Group 5. Immunohistochemical changes were significantly lower in Group 4 than in Group 3. Axonal degeneration was also higher in Group 4 than in Group 3. CONCLUSION: Gabapentin promotes neurological recovery histopathologically in peripheral nerve injury due to its neuroprotective properties. Our study results show that gabapentin can be used as an adjunctive therapy to primary surgical treatment after peripheral nerve injury.

Prophylactic Bevacizumab May Mitigate Radiation Injury: An Experimental Study.

BACKGROUND: Stereotactic radiosurgery (SRS) is widely used to treat brain pathologies alone or in concert with other treatment modalities. However, there are some side effects, such as radiation injury characterized by edema and necrosis in peripheral tissues, that must be managed. A new treatment agent against this side effect is bevacizumab, which targets increased vascular endothelial growth factor (VEGF) as a prominent etiologic factor in radiation injury. In this study, we created a rat experimental model to describe the effects of both radiation and the anti-VEGF monoclonal antibody bevacizumab following high-dose SRS, and to compare the effects of prophylactic and delayed-onset bevacizumab treatment. METHODS: Fifty-four adult male Wistar rats were allocated into 9 groups based on differing Gamma-knife surgery (GKS) doses and bevacizumab treatment protocols. After 12 weeks, the rats' right frontal lobes were examined with hematoxylin and eosin staining and immunohistochemistry analysis via VEGF and CD31 antibodies. RESULTS: Radiation necrosis occurred to varying degrees in all irradiated animals between 3 and 10 weeks post-SRS. Higher GKS dose (50% isodose of 100 Gy) led earlier necrosis and prophylaxis of bevacizumab at this dose was associated with delayed onset of necrosis. Moreover, prophylactic bevacizumab mitigated the effects of radiation necrosis following GKS at both doses, whereas this effect was not prominent with late initiation of bevacizumab (treatment protocol). CONCLUSIONS: Our findings show that the onset and degree of radiation injury are affected by the GKS dose and protocol of bevacizumab administration.

A Rare Pediatric Case of Neurocysticercosis Misdiagnosed As Brain Abscess.

Neurocysticercosis is a parasitic infection of the central nervous system caused by the larval stage of Taenia solium. Although this zoonotic infection is one of the major public health problems in some developing countries, it is extremely rare in Turkey. In this article, we present the case of a pediatric patient with neurocysticercosis who was misdiagnosed with brain abscess because of focal seizures in another hospital.

Extensive middle cranial fossa arachnoid cysts and different clinical presentation in two patients.

Arachnoid cysts (ACs), particularly suprasellar cysts, cause a wide spectrum of endocrine disorders. Herein, we report two patients diagnosed with an extensive AC in the middle cranial fossa while being investigated for etiologies of precocious puberty and short stature. One of them required surgery due to his pubertal disorders associated with compression effects of cyst. After surgery, his puberty progression was regressed within one year. On the other hand, surgery was not planned for the second patient considering of his cranial imaging findings and the extremely low incidence of growth hormone (GH) deficiency caused by middle fossa AC (MFAC). We started treatment with recombinant human GH and no complication was found during treatment follow-up. Endocrine disorders associated with MFACs are extremely rare. By presenting with these two cases, we aimed to remain our fellow physcians that ACs can be possibly cause of endocrine disorders. Clinicians should be careful evaluating endocrine disorders because real cause may not be cyst itself but masked by it.