Thymoquinone ameliorates delayed cerebral injury and cerebral vasospasm secondary to experimental subarachnoid haemorrhage.

AIM OF THE STUDY: Among subarachnoid haemorrhage (SAH) patients, delayed cerebral injury (DCI) and infarction are the most important causes of death and major disability. Cerebral vasospasm (cVS) and DCI remain the major cause of death and disability. Thymoquinone (TQ) is the substance most responsible for the biological activity of nigella sativa (NS) and is useful in the treatment of ischaemic and neurodegenerative diseases, oxidative stress, inflammatory events, cardiovascular and neurological diseases. We conducted an experimental study aimed to investigate the preventive and corrective effects of TQ. MATERIALS AND METHODS: 24 Sprague-Dawley rats were randomly divided into three groups. The first was the control group which was a sham surgery group. The second group was the SAH group where the double haemorrage SAH protocol was used to induce vasospasm. The third group was the SAH+TQ group, where cVS was induced by the SAH protocol and the animals received oral 2 cc thymoquinone solution for seven days at a dose of 10 mg/kg, after the induction of SAH. The rats were euthanised seven days after the first procedure. The degree of cerebral vasospasm was evaluated by measuring the basilar artery luminal area and arterial wall thickness. Apoptosis was measured by the western blot method at brainstem neural tissue. Oxidative stress was measured by the Erel Method. Endothelin-1 was measured with ELISA analysis at blood. Statistical analysis was performed. RESULTS: Endothelin-1 values were found to be statistically significantly lower in the control and SAH+TQ groups compared to the SAH group (P < 0.001). Mean lumen area values were significantly higher in the control and SAH+TQ groups than in the SAH group (P < 0.001). In the control and SAH+TQ groups, wall thickness values decreased significantly compared to the SAH group (P < 0.001). OSI values were significantly lower in the control and SAH+TQ groups than in the SAH group (P < 0.001). Apoptosis was significantly lower in the control and SAH+TQ groups than in the SAH group (P < 0.001). CONCLUSION: Our results show that post-SAH TQ inhibits/improves DCI and cVS with positive effects on oxidative stress, apoptosis, ET-1, lumen area, and vessel wall thickness, probably due to its anti-ischaemic, antispasmodic, antioxidant, anti-inflammatory, anti-apoptotic and neuroprotective effects.

Single-stage planning for total cure of grade III-V brain arteriovenous malformations by embolization alone or in combination with microsurgical resection.

PURPOSE: There are no established guidelines for treatment of Spetzler-Martin grade III-V brain arteriovenous malformations (bAVMs). The purpose of this study is to report our institutional experience in total obliteration/eradication of grade III-V bAVMs by single-stage planning of embolization combined with microsurgical resection when necessary. METHODS: All patients harboring Spetzler-Martin (S-M) grade III-V bAVMs treated with single-stage planning between January 2006 and January 2018 were retrospectively reviewed. This treatment paradigm is applicable only to surgically accessible bAVMs and does not include deep-seated bAVMs. Indications for treatment, clinical presentation, imaging characteristics, and treatment outcomes were analyzed. Outcomes were assessed based on modified Rankin Scale. RESULTS: A total of 31 patients were identified. Seventeen patients (54.8%) presented with hemorrhage, 10 (32.3%) with seizures, 3 (9.7%) with headaches, and 1 (3.2%) with progressive neurological deficit. Based on S-M grading system, 25 patients (80.6%) harbored grade III bAVM, 5 patients had grade IV bAVMs (16.1%), and 1 patient (3.2%) had a grade V bAVM. There were no treatment-related complications in 24/31 (77.4%) patients. Of the total of seven patients with complications, four patients had clinical deterioration. The long-term (> 6-month), non-disabling morbidity (mRS ≤ 2) rate was 6.5%. The long-term, disabling morbidity rate was 3.2% with a mortality of 3.2%. Complete angiographic obliteration was achieved in 30/31 (96.8%) patients. CONCLUSION: Single-stage treatment strategy can be considered as an alternative to multistage embolization prior to surgery in grade III-V bAVMs. In this study, a high rate of total obliteration with relatively low rates of permanent morbidity and mortality was achieved.

Rapid improvement in visual loss with cabergoline treatment in a giant prolactinoma case: 5 years survey.

Giant prolactinoma is a rare subset of macroadenomas. Limited studies demonstrated which therapy could be successfully used in the first-line therapy of giant prolactinoma. We presented a case with a 54 × 40 × 40 mm pituitary adenoma and optic chiasmatic compression with left sphenoid sinus invasion. The tumor caused a loss of visual field of the right side. Cabergoline treatment was started with dose of 1.5 mg/week. Fifteen days later, the clinical visual acuity examination showed a significant improvement in the patient with visual field defect. After the five years follow-up magnetic resonance imagining showed reduction of the adenoma size (17 × 12 mm) was significant. Our findings suggest that, cabergoline can be used as a first-line therapy in giant prolactinomas because tumoral shrinkage without a surgical procedure and rapid improvement in visual field defect is achieved with this medical treatment.

Recurrent Meningitis After a Post-Traumatic Intradiploic Arachnoid Cyst: A Case Report.

Intradiploic arachnoid cysts are infrequent but benign lesions of the central nervous system. Etiologically, they can be non-traumatic or post-traumatic in origin. We present an unusual case of a post-traumatic intradiploic arachnoid cyst presented with recurrent meningitis episodes. A 68-year-old female patient was admitted to the emergency department with fever and loss of consciousness, with a history of cranial operation due to a gunshot injury to the left occipital bone 45 years ago. On the patient's initial examination, nuchal rigidity was detected; Kernig's and Brudzinski's signs were positive. A lumbar puncture has been performed, and the patient is diagnosed with meningitis. The patient had been admitted to the emergency department with rhinorrhea after a minor blunt head trauma six years ago. As we understood from the patient's medical records, a couple of millimetric non-specified pneumocephalus areas, located next to the sella turcica, were detected on the cranial non-contrast-enhanced CT scan after the minor blunt trauma to the frontal bone. However, there was no sign of any obvious skull base fracture. The patient was hospitalized for five days and discharged on the sixth day without any complaints. After the discharge, the patient was admitted to other hospitals five times in the last five years with fever and anxiety. On all her admissions, the patient was diagnosed with CSF-culture-negative meningitis and treated with different unknown antibiotics. Magnetic resonance imaging (MRI) showed some irregularities and thinning at the inner table of the left occipital bone; there was an enlargement of the diploic distance of the occipital bone on the left side. MR cisternography showed cerebrospinal fluid (CSF) fistulizing areas just below the thickened and irregular part of the occipital bone. CSF fistula was communicated with the left lateral ventricle. The occipital horn of the left lateral ventricle was enlarged. We performed a surgical repair in order to cover the defective areas of the occipital and mastoid bones. The retromastoid approach was used. Pedunculated muscle flaps to cover the defective bony areas are used and secured with fibrin glue. There is no evidence of recurrence during the one-year follow-up period of the patient. We present this unusual case to emphasize that if post-traumatic intradiploic arachnoid cysts remain untreated, severe complications, such as episodes of recurrent meningitis, may occur. Although a few cases of these cysts are reported in the literature, a case of post-traumatic intradiploic arachnoid cyst presenting with recurrent meningitis has not been reported. In patients with recurrent meningitis, when no prominent etiology is found and if there is a trauma to the related bone in the patient's history, post-traumatic intradiploic arachnoid cyst should be included in the differential diagnosis.

CT-guided percutaneous translaminar approach for blood patching: case report and technical note.

In this article the authors describe a novel technique for performing epidural blood patch (EBP) by percutaneous CT-guided translaminar approach in challenging cases where interlaminar approach is not possible. A 24-year-old woman with medical history of multiple spinal surgeries and instrumentations for the treatment of scoliosis, presented 3 months post-operatively with acute and severe orthostatic headaches that began 1 week after surgery. Neurological examination was normal. Brain magnetic resonance imaging (MRI) showed mild thickening and contrast enhancing in the bilateral dura. Computed tomography (CT) myelography revealed CSF leakage in the level of T3 vertebra. EBP was attempted using fluoroscopic and then CT guidance; however, despite multiple attempts, the epidural space could not be accessed through the interlaminar route due to extensive instrumentation of the spine and profound structural bony abnormalities. EBP was performed successfully via a CT-guided translaminar approach using an Ostycut trephine needle (Angiomed(®)/Bard, Karlsruhe), without complications.

Intraoperative Fluorescein Sodium Videoangiography in Intracranial Aneurysm Surgery.

OBJECTIVE: Fluorescein sodium (FNa) videoangiography (VA) was performed to evaluate blood flow within vessels and exclusion of the aneurysm after surgical clipping of intracranial aneurysms. The aim of this study was to report results of FNa-VA in a case series, including benefits and limitations of the technique, and compare intraoperative findings with postoperative cerebral angiography to assess reliability of FNa-VA. METHODS: The study included 64 aneurysms in 50 consecutive patients. Following clip ligation of the aneurysm, 100 mg of FNa was administered intravenously. The microscope light was switched to the FL560 integrated fluorescence module. Aneurysm sac, parent arteries, and perforating arteries were observed. RESULTS: FNa-VA promoted real-time assessment of the surgical field in three-dimensional view through the binoculars with good image quality. In 79.68% of aneurysms, FNa-VA confirmed satisfactory clip application, as FNa did not penetrate into the aneurysm. In 14.06% of aneurysms, a homogeneous yellow-green color change occurred, which was accepted as a false-positive sign. In 6.25% of aneurysms, FNa seeped into the aneurysm emitting a heterogeneous green signal, which slowly dispersed throughout the sac. Postoperative angiography revealed satisfactory results. Small neck remnants were present in 5 patients, and mild parent artery stenosis was found in 3 patients. No ischemic event occurred secondary to parent artery or perforating artery occlusion. CONCLUSIONS: FNa-VA adds greatly to the safety of surgical treatment of intracranial aneurysms, particularly in lesions situated in deep locations, by enabling real-time inspection, which facilitates safer manipulation and evaluation of structures in question.

Tissue Thiol Concentration in High-Grade Gliomas: Is There any Association Between IDH1 Mutation Presence and Tumoral Cellular Antioxidant Defense?

AIM: To assess and compare the antioxidant capacities of high-grade gliomas (HGG) according to their grades and the presence of isocitrate dehydrogenase 1 (IDH1) mutation using tissue thiol level measurement. MATERIAL AND METHODS: Tissue thiol concentrations were measured in 41 HGG samples and 21 healthy brain tissues obtained from autopsy procedures, which were performed within the first 4 hours of death. All samples were stored at ?80°C, and a thiol quantification kit was used in evaluating tissue thiol levels. The Number Cruncher Statistical System was used for statistical analyses to detect the differences between the control group and the HGG group, which was also divided into subgroups according to their grade and IDH1 mutation presence. RESULTS: The tissue thiol levels of HGGs were found to be higher than the control group (p=0.001). Although the median thiol levels of Grade 4 gliomas were higher than those of Grade 3, no statistically significant difference was noted (p=0.076). When all tumors were compared according to the IDH1 mutation presence, IDH1-negative (IDH1-) HGGs had higher thiol contents than IDH1 mutant (IDH1+) HGGs (p=0.001). The thiol levels of Grade 4 IDH1- gliomas were statistically significantly higher than of Grade 3 gliomas (p=0.023), but no statistically significant difference between the thiol levels of Grade 3 and Grade 4 IDH1+ tumors was noted (p=0.459). CONCLUSION: We have demonstrated the higher thiol concentrations of HGGs, particularly IDH1- ones. The sulfhydryl contents of gliomas as an indicator of tumoral antioxidant capacity may be responsible for the treatment resistance of IDH1- gliomas, the mechanism of which is not clear. Thiols can be a novel target for treatment, considering the unsatisfactory results of current modalities for HGGs.

Aneurysmal frontal bone cyst in a child with history of acute lymphoblastic leukemia: a case of rare location and history.

SUMMARY: Authors present an 11-year-old female admitted with a 3-month history of painless forehead mass. The mass was located in the left frontal area and was pronounced on inspection and palpation. Neurologic examination revealed no abnormalities. The patient was diagnosed for acute lymphoblastic leukemia 5 years ago and had been treated. The patient was under observation by the pediatric oncology clinic with remission state since 3 years. Brain computed tomography and magnetic resonance imaging revealed a cystic bone lesion in the right frontal bone. A preoperative diagnosis of myeloproliferative disorder was made and it was surgically resected and cranioplasty with porous polyethylene sheets (Medpor, Porex Surgical Inc, GA) was performed in the same stage. Pathologic examination revealed an aneurysmal bone cyst. The patient recovered with complete resolution of symptoms. Although rare lesions, aneurysmal bone cysts must be considered in the differential diagnosis of calvarial mass lesions.

The Expression of MIR17HG Protein as a Potential Therapeutic Target in Meningioma.

BACKGROUND: MIR17 host gene (MIR17HG) is a potential therapeutic target for some cancer types. The aim of this study was to assess MIR17HG protein levels in patients with meningioma who had not been reported previously in the literature and comparing with normal meninges tissues. METHODS: MIR17HG protein levels were measured in 46 samples including 25 meningioma tissues procured during surgery and 21 normal meninges tissues obtained within 4 hours of death during autopsy procedures. Each sample was stored at -80°C until the evaluation of MIR17HG protein using a sandwich enzyme-linked immunoassay principle. Results were compared between the groups. RESULTS: MIR17HG protein levels were significantly higher in meningioma tissues compared with controls and difference was statistically significant (P = 0.012). Both World Health Organization grade I and grade II meningiomas had higher MIR17HG protein levels compared with controls and differences were statistically significant (P = 0.026 for grade I and P = 0.042 for grade II). Receiver operating characteristic curve analysis was performed to determine the cutoff of MIR17HG protein value in differentiating meningioma and control groups. At the cutoff value for MIR17HG protein of >0.0998 ng/mL, the sensitivity was 73.91%, 71.43%, and 77.78% and area under the curve was 0.756, 0.753, and 0.761 for meningioma group, grade I, and grade II subgroups, respectively, and specificity was 69.23% for each group. CONCLUSIONS: MIR17HG protein expression was found to have a higher level in meningiomas than in normal meninges tissues in our study. Considering the recurrence and irresectability for some meningiomas, which require further treatment, MIR17HG may be a new target for treatment in meningiomas and our study will shed light on further studies.

The effect of high mobility group box-1 protein on cerebral edema, blood-brain barrier, oxidative stress and apoptosis in an experimental traumatic brain injury model.

Traumatic brain injury (TBI) is one of the important reason of morbidity and mortality. While the primary injury due to mechanical impact is unavoidable, the secondary injury which is formed as a result of primary injury and thought to occur due to neuroinflammation in the forefront can be prevented and by this way mortality and morbidity can be reduced. High mobility group box-1 (HMGB1) is a protein that triggers the neuroinflammatory process by being released from the nucleus of necrotic tissues after primary injury. The aim of this study is to investigate the effects of HMGB1 on its receptors TLR4 and RAGE, cerebral edema, blood-brain barrier, oxidative stress and apoptosis causing secondary damage in an experimental traumatic brain injury model. Weighing between 280-320 g, 10 to 12 weeks-old, a total of 30 adult male Sprague-Dawley rats were used for the experiments. The rats were randomly assigned to 3 groups: 1) Control, 2) TBI and 3) TBI + ethyl pyruvate group (n = 10 per group). Right parietal cortical contusion was made by using a weight-dropping TBI method. Brain samples were harvested from pericontusional area at 24 h after TBI. HMGB1, TLR4, RAGE, occludin, claudin-5, ZO-1 levels are investigated by western blot analyses and immunohistochemistry examinations. HMGB-1, TLR4 and RAGE expressions increased after TBI. Major tight junction proteins in the blood-brain barrier: occludin, claudin-5 and ZO-1 expressions decreased after TBI. Brain edema increased after TBI. Also, proapoptotic bax and active caspase 3 expressions increased, antiapoptotic bcl-2 levels decreased after TBI. Total oxidant status and oxidative stress increased, total antioxidant status decreased after TBI. HMGB-1 protein plays a key role in the pathophysiology of traumatic brain injury.

Duraplasty using autologous fascia lata reenforced by on-site pedicled muscle flap: technical note.

OBJECTIVE: Postoperative cerebrospinal fluid (CSF) leak is a common complication in the practice of neurosurgery, and various surgical techniques were described to overcome and manage this problem. Besides not applying watertight closure of the duraplasty, the inviability and the poor vascularization of the graft and/or the dura (eg, reoperations, multiple operations, or cranial radiotherapy) may lead to delayed healing of the suture site and resultant persistent CSF leaks. We present a simple technique that uses on-site muscle flap with pedicle to supply and vascularize the autologous fascia lata, preserving the viability of the graft and reenforcing its healing ability. METHODS: We applied this technique in 6 patients with postoperative CSF leaks. After harvesting a fascia lata graft with appropriate size from the patients, the graft was sutured to dural defect in watertight fashion. The suboccipital, temporal, and temporal muscles in 4 patients who had posterior fossa duraplasty, in 1 patient who had pterional craniotomy, and in 1 patient who had subtemporal craniotomy, respectively, were dissected, stretched, and sutured to the fascia graft covering the dura graft suture site and then reinforced by Tisseel fibrin glue (Baxter Healthcare Corporation, Deerfield, IL). Postoperatively, CSF lumbar drain was kept open for 72 hours with pressure wound dressing. The technical nuances are illustrated. RESULTS: Cerebrospinal fluid leaks were controlled successfully in 5 patients without recurrence. One patient with posterior fossa duraplasty had recurrence of CSF leak that required reexploration 21 days after the first surgery and a second dural repair in a site distant from the fascia lata attachment. During reexploration intraoperatively, the fascia lata graft was inspected and studied, which has shown the healing of the dura graft site and the graft neovascularization. CONCLUSIONS: Duraplasty using autologous fascia lata reenforced by on-site pedicled muscle flap is an effective technique to control CSF leak, especially when dura is poorly vascularized and less viable. The unfortunate recurrence of CSF leak and reexploration in the seventh patient helped us to observe the effectively healed dural defect with profound early postoperative vascularization of the graft, supporting our idea about the effectiveness of this technique.

Bilateral C1-C2 claw for atlantoaxial instability.

OBJECTIVE: Atlantoaxial stability can be achieved by laminar hook systems via posterior approach. This technique is much more safer than using screws. We presented our experience with the C1-C2 claw procedure. METHODS AND MATERIAL: Seven patients with atlantoaxial instability were operated by using C1 and C2 hooks, rods and transverse connector at Neurosurgery Clinic of Istanbul University Cerrahpasa Medical Faculty between the years 2005 and 2008. RESULTS: Satisfactory stabilization was achieved in all patients. Operative complication or instrumentation failure was not observed. CONCLUSIONS: C1-C2 claw is a safe technique and adequate stabilization is achieved with the use of a transverse connector.

Glioblastoma Stem Cells and Comparison of Isolation Methods.

BACKGROUND: Glioblastoma (GBM) is the most aggressive and the most common primary brain tumor. Over the last few years, studies have identified many genetical and phenotypical molecular situations for developing new treatment modalities in patients with GBM. Nevertheless, main problem for the GBM is radio-chemotherapy resistance and relapse after the surgery. The identification of glioma stem cells and microenvironmental influences has created a paradigm shift in targets of therapy. Current studies have shown that glioma stem cell is responsible for aggressiveness, recurrence and resistance to therapy of GBM. GBM stem cell isolated from human GBM multiforme fresh tissue samples is important both for curative therapeutic options and personalized targeted therapy. The purpose of this study was to determine the most suitable isolation method of GBM stem cells (GSCs). METHODS: Tumor tissue sample was obtained during the surgical resection of lesion in patients with the diagnosis of GBM. Tumor stem cell isolation from tissue was performed in three different ways: 1) GBM cell isolation with trypsin; 2) GBM cell isolation with brain tumor dissociation Kit (BTD Kit); and 3) GBM cell isolation with tumor dissociation enzyme (TDE). RESULTS: We showed that GSCs were isolated from tumor specimen using flow cytometry and immunofluorescence staining. Our study showed that isolation with BTD Kit is the most suitable method to isolate GBM tissue-derived glial tumor stem cells. CONCLUSIONS: The development of alternative personalized therapies targeting brain tumor stem cell is urgently needed. It is important to understand the fundamental mechanisms of driving stem cells. If their life cycle mechanisms can be identified, we can control the growth of GBM.

Effects of Intrathecal Verapamil on Cerebral Vasospasm in Experimental Rat Study.

BACKGROUND: Verapamil, a calcium-channel blocker, has shown promising results on cerebral vasospasm. However, it has not yet been accepted for treatment or prevention purposes because of the associated side effects. Although the effective results of nimodipine and nicardipine's intrathecal administration are well known, intrathecal verapamil has not been considered earlier. We used an experimental subarachnoid hemorrhage-induced vasospasm model for the evaluation of vasodilator and neuroprotective effects of intrathecal verapamil. METHODS: A total of 24 Sprague-Dawley rats were randomly divided into the following 3 groups: group 1 (sham), group 2 (subarachnoid hemorrhage), and group 3 (verapamil). A double hemorrhage method was used. Group 2 did not receive any treatment. Verapamil (Eporon, Dem Ilac, Turkey) at a dose of 1000 µg/kg was given intrathecally to group 3 rats. The animals were euthanized on day 7 of the procedure. Arterial wall thickness and lumen diameter in the basilar arterial cross-sectional areas, endothelin-1 serum level, oxidative stress index, and apoptosis were measured in all groups. RESULTS: In the verapamil group, wall thickness, endothelin-1 level, oxidative stress index, and apoptosis were found to be significantly lower than the subarachnoid hemorrhage group, but the lumen diameter was found to be greater. Intrathecal verapamil was found to decrease vasospasm parameters and apoptosis and increase the antioxidant and antiapoptotic pathways. CONCLUSIONS: Our findings suggest that intrathecal verapamil can prevent vasospasm, oxidative stress, and apoptosis after experimental subarachnoid hemorrhage.

NRGN, S100B and GFAP levels are significantly increased in patients with structural lesions resulting from mild traumatic brain injuries.

OBJECTIVE: To determine whether serum neurogranin (NRGN), glial fibrillary acidic protein (GFAP), and calcium-binding protein S100 beta (S100B) levels are associated with traumatic intracranial lesions compared to computed tomography (CT) findings of patients with mild traumatic brain injury (mTBI). PATIENTS AND METHODS: The cross-sectional study cohort included 48 patients who were admitted to the Emergency Department with a complaint of mTBI, a Glasgow Coma Scale score of 14-15, and at least one symptom of head trauma (i.e., post-traumatic amnesia, nausea or vomiting, post-traumatic seizures, persistent headache, and transient loss of consciousness). Blood samples and CT scans were obtained for all patients within 4 h of injury. Age-matched patients without intracranial traumatic pathology (CT-) were recruited as a control group. Blood samples were measured for NRGN, GFAP, and S100B levels. RESULTS: Of 48 patients, 24 were CT + and had significantly higher serum NRGN (5.79 vs. 2.95 ng/mL), GFAP (0.59 vs.0.36 ng/mL), and S100B (1.72 vs.0.73 µg/L) levels than those who were CT- (p = 0.001, p = 0.026, and p < 0.001, respectively). ROC curves showed that NRGN, GFAP, and S100B levels were sufficient to distinguish traumatic brain injury in patients with mTBI. At the cut-off value for NRGN of 1.87 ng/mL, sensivity was 83.3%, and specificity was 58.3%. At the cut-off value for GFAP of 0.23 ng/mL, sensivity was 75% and specificity was 62.5%. The optimal cut-off value for S100B was 0.47 µg/L (95.8% sensitivity and 62.5% specificity). CONCLUSION: This is the first study to evaluate NRGN in human serum after mTBI. We confirmed that NRGN levels were significantly higher in CT + patients than CT- patients in the mTBI patient population. Future studies of larger populations and different age groups (especially pediatric) can help reduce the number of CT scans as a reliable and noninvasive diagnostic tool for evaluating NRGN protein levels in mTBI patients with a low probability of intracranial lesions.

Intracranial hypotension following scoliosis surgery: dural penetration of a thoracic pedicle screw.

The authors report on a 14 years old female with intracranial hypotension who had a history of spinal instrumentation surgery for scoliosis 3 months prior to her admission. She had been diagnosed with migraine in a neurology clinic and was under medical therapy when presented. During the investigation process, a right thoracic pedicle screw, which was penetrating and transversing the dura mater at the T3-T4 level was identified. The diagnosis and management of such a case is discussed. Knowledge of this entity is of extreme importance to spine surgeons, in order to prevent delayed diagnosis and possible complications.

Elevated cerebrospinal fluid and serum YKL-40 levels are not associated with symptomatic vasospasm in patients with aneurysmal subarachnoid haemorrhage.

YKL-40 is a newly discovered matrix protein that is thought to be released during the acute stages of inflammation. It has recently been speculated that YKL-40 may serve as a specific serological marker of neutrophil function at the site of tissue inflammation. Our aim was to determine whether the levels of YKL-40 in both the cerebrospinal fluid and sera of 22 patients with aneurysmal subarachnoid haemorrhage were associated with either vasospasm or outcome. The levels were also compared with those of 16 control patients with hydrocephalus. We found that patients with aneurysmal subarachnoid haemorrhage had significantly higher YKL-40 levels in both cerebrospinal fluid and serum than controls. However, elevated YKL-40 levels were not associated with symptomatic vasospasm or 6-month outcome. We show that elevated YKL-40 levels are not correlated with the severity of subarachnoid haemorrhage and cannot be used as a serological marker of inflammation in patients with an aneurysm rupture.

Expression of hypoxia inducible factor-1alpha in tumors of patients with glioblastoma multiforme and transitional meningioma.

Hypoxia-inducible factor-1 alpha (HIF-1alpha) is the major transcriptional factor involved in the adaptive response to hypoxia. The aim of this study was to assess HIF-1alpha in 22 patients with transitional meningioma (TM) and 26 patients with glioblastoma multiforme (GBM). HIF-1alpha was assessed using a commercially available enzyme-linked immunosorbent assay-based HIF-1 transcription factor assay. Levels of HIF-1alpha in TM and GBM were measured using optical density at 450nm, and median values were found to be 0.35 for TM and 0.37 OD for GBM, respectively. There was no statistically significant difference between the two types of tumor (p=0.264). These findings indicate that HIF-1alpha is elevated in both TM and GBM, suggesting that although hypoxia is one of the most important and powerful stimuli for HIF-1alpha elevation and consequently angiogenesis, other mechanisms may play roles in HIF-1alpha stimulation in benign brain tumors such as TM.

Investigation of Survivin Gene Polymorphism and Serum Survivin Levels in Patients with Brain Tumors.

BACKGROUND/AIM: The single nucleotide polymorphism -31C/G identified in the survivin gene promoter seems to be associated with over-expression of survivin, an anti-apoptotic protein. In gliomas, increased survivin expression correlated with decreased survival. The aim of the study was to investigate whether survivin gene polymorphism associates with benign and malignant brain tumors and whether it affects survivin serum levels. PATIENTS AND METHODS: Survivin polymorphism -31C>G was genotyped in 82 patients with brain tumors and 65 healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and survivin levels were evaluated by enzyme-linked immuno sorbent assay (ELISA) in patients and controls. RESULTS: Serum survivin levels in patients with malignant tumors were higher than patients with benign tumors (p<0.001). Survivin levels in patients with malignant glial tumors and the frequency of the GG genotype were higher than in patients with benign tumors (p=0.04) and controls (p=0.05). The prevelance of the survivin gene promoter polymorphism -31C>G did not differ between patients and controls. CONCLUSION: Survivin promoter -31C>G gene polymorphism seems to be associated with serum survivin levels in brain tumors of different grades and histologies.

Glutathione peroxidase, glutathione reductase and protein oxidation in patients with glioblastoma multiforme and transitional meningioma.

PURPOSE: The aim of this study was to assess glutathione peroxidase (GPx), glutathione reductase (GRx) and protein oxidation (POx) levels in patients with glioblastoma multiforme (GBM) and transitional meningioma (TM) and to compare with normal brain tissues. METHODS: GPx, GRx and POx levels were measured in 48 brain tumors obtained during surgery and 15 normal brain tissues that were collected during autopsy. Results were compared between two groups. RESULTS: GPx and GRx activities were significantly lower in GBM and TM when compared to controls and the difference was statistically significant (P = 0.0001). Furthermore, the decrease in enzyme activities was more evident in GBM than in TM. In contrast, POx levels were found to be higher in both GBM and TM compared to controls and showed statistically significant difference (P = 0.00001). Increase in POx levels was clearer in GBM than TM. CONCLUSIONS: GPx and GRx decreased and POx increased significantly in both GBM and TM when compared to normal brain tissues. Further, clinical studies with a larger patient population are required to show the role(s) of antioxidant enzymes in brain tumors more accurately.