Effect of MCI-186 on Lipid Peroxidation in Experimental Traumatic Brain Damage in Rats.

Objective: Brain damage occurs in many clinical conditions, including trauma, ischemia, and hypertension. Reactive oxygen products and lipid peroxidation are responsible for the brain damage that occurs in these clinical conditions. We investigated whether MCI-186 (3-methyl-1-phenyl-2-pyrazoline-5-one), a free radical binding agent on lipid peroxidation, affects malondialdehyde (MDA), glutathione (GSH), and glutathione peroxidase (GPx) levels in traumatic brain damage. Methods: The traumatic brain damage model, modified by Feeney, was performed on 28 male Wistar rats separated into 4 groups. The MDA, GSH, and GPx levels in the brain tissues of each group were studied. Results: MDA levels in the traumatized group were significantly higher than those in the sham and MCI-186 groups (p<0.05), while GSH levels were significantly higher in the sham group than in the trauma and solvent groups (p<0.05). No significant difference was observed between the sham and MCI-186 groups (p>0.05). Although the average GPx level was higher in the sham and MCI-186 groups, no significant difference was found between groups. Conclusion: Reactive oxidation products significantly decreased in the MCI-186 group. Thus, MCI-186 can be used as a free radical-binding agent in traumatic brain damage.

Histopathological Evaluation of the Effects of CAPE in Experimental Spinal Cord Injury.

AIM: < /B > Spinal cord injuries negatively affect the individuals and the life quality of their families due to neurological deficits caused by trauma. The prevalence of spinal cord injury is 15-45/1 million in the world. Caffeic acid phenethyl ester (CAPE) is the most active component of propolis and has neuroprotective, anti-oxidant and anti-apoptotic effects. Our aim was to determine the effects of CAPE on the prevention of secondary injury and to compare with methylprednisolone. MATERIAL AND METHODS: Forty rats were divided into 4 groups. The control group did not undergo surgery (Group I), only trauma group (Group II), trauma+CAPE treatment group (Group III), and trauma+methylprednisolone treatment group (Group IV). Histopathological assessment was performed with two staining methods as hematoxylin-eosin (HE) and terminal deoxynucleotidyl Transferase Biotin - dUTP Nick End Labeling (TUNEL). The groups were statistically compared. RESULTS: The apoptotic cells decreased in treatment groups compared with the trauma. CAPE has more anti-apoptotic effect than methylprednisolone. The histological difference between the Group II, and Groups III and IV was statistically significant. CONCLUSION: CAPE has a positive effect on spinal cord injuries by preventing apoptosis.

Effectiveness of physical therapy and rehabilitation programs starting immediately after lumbar disc surgery.

AIM: The aim of this randomized study was to compare exercise program to control group regarding pain, back disability, behavioural outcomes, global health measures and back mobility who underwent microdiscectomy operation. MATERIAL AND METHODS: Thirty patients who underwent lumbar microdiscectomy were randomized into exercise and control groups. After surgery, patients in the exercise group undertook a 12-week home based exercise program, started immediately postsurgery and concentrated on improving strength and endurance of the back, abdominal muscles, lower extremities and mobility of the spine and hips. Outcome measures were: Oswestry Disability Index (ODI), Beck Depression scale, lumbar schober, Visual Analogue Scale (VAS), return to work (return-to-work status), generic functional status (SF-36). RESULTS: Treatment compliance was high in both groups. Surgery improved pain, disability, general health status, lumbar mobility and behavioural status. After the exercise program, the exercise group showed further improvements in these measures at 12 week after surgery. CONCLUSION: A 12-week postoperative exercise program starting immediately after surgery can improve pain, disability, and spinal function in patients who have undergone microdiscectomy.

Application of lumbar drainage in vasospasm after spontaneous subarachnoid hemorrhage and prevention of late cerebral infarction.

Cerebral vasospasm, especially delayed cerebral ischemia following subarachnoid hemorrhage (SAH) is the most important complication that effects mortality and morbidity of patients with intracranial aneurysms. The presence of cerebral vasospasm has been correlated with an increase in mortality in the first 2 weeks after SAH. Despite clinical studies and research, the etiopathogenesis of cerebral vasospasm is not understood exactly and there is not yet an effective therapy. The aim of our study was to investigate the effect of application of lumber drainage on vasospasm and delayed cerebral infarction following SAH and to examine the incidence of complications. Patient groups were determined by retrospective screening of 70 patients who underwent a surgical operation at the Osmangazi University Medical Faculty Department of Neurosurgery between 2009 and 2013 after a diagnosis of ruptured aneurysmal SAH. After the application of lumbar drainage, the complications and mortality after aneurysm surgery was significantly decreased and correlated with the amount of hemorrhagic cerebrospinal fluid drainage.

Neuroprotective Effect of Resveratrol on Acute Brain Ischemia Reperfusion Injury by Measuring Annexin V, p53, Bcl-2 Levels in Rats.

BACKGROUND: Cerebral ischemia is as a result of insufficient cerebral blood flow for cerebral metabolic functions. Resveratrol is a natural phytoalexin that can be extracted from grape's skin and had potent role in treating the cerebral ischemia. Apoptosis, a genetically programmed cellular event which occurs after ischemia and leads to biochemical and morphological changes in cells. There are some useful markers for apoptosis like Bcl-2, bax, and p53. The last reports, researchers verify the apoptosis with early markers like Annexin V. METHODS: We preferred in this experimental study a model of global cerebral infarction which was induced by bilateral common carotid artery occlusion method. Rats were randomly divided into 4 groups : sham, ischemia-reperfusion (I/R), I/R plus 20 mg/kg resveratrol and I/R plus 40 mg/kg resveratrol. Statistical analysis was performed using Sigmastat 3.5 ve IBM SPSS Statistics 20. We considered a result significant when p<0.001. RESULTS: After administration of resveratrol, Bcl-2 and Annexin levels were significantly increased (p<0.001). Depending on the dose of resveratrol, Bcl2 levels increased, p53 levels decreased but Annexin V did not effected. P53 levels were significantly increased in ishemia group, so apoptosis is higher compared to other groups. CONCLUSION: In the acute period, Annexin V levels misleading us because the apoptotic cell counts could not reach a certain level. Therefore we should support our results with bcl-2 and p53.

Early decompressive surgery after combined intra-venous thrombolysis and endovascular stroke treatment.

BACKGROUND AND PURPOSE: The prognosis of malignant middle cerebral artery infarctions (MCA) is poor. The poor prognosis is attributable to the severe cerebral edema that causes a brain herniation and death. Decompressive surgery reduces mortality and may further improve patient outcomes. However, the safety and effectiveness of decompressive surgery in patients who underwent combined intravenous (IV) thrombolysis and endovascular stroke treatment are not certain. Moreover, the evidence on the timing of decompressive surgery is lacking. METHODS: The purpose of the open, prospective and non-randomized study was to compare the outcome and complication rates of patients with malignant MCA strokes who underwent early decompressive surgery after combined intravenous thrombolysis and endovascular treatment with those of decompressive surgery patients without prior recanalization treatment strategy. All patients underwent decompressive surgery within 24h of symptom onset. RESULTS: Thirty patients were included in the study. Twelve of the 30 patients were treated with combined IV thrombolysis and endovascular approach and 18 patients received standard treatment. The proportion of patients with a modified Rankin score ≤3 at the sixth month follow-up was 33% in the standard group and 44% in the combined treatment group (p=0.712). Mortality, and major and minor complications including symptomatic intracerebral hemorrhage after decompressive surgery did not differ between the two groups (p>0.05). CONCLUSION: Early decompressive surgery can be safely performed in patients who received combined IV thrombolysis and endovascular treatment and there was no difference in outcome of these patients compared with patients who did receive the standard medical treatment before early decompressive surgery.

Erythropoietin prevents nitric oxide and cathepsin-mediated neuronal death in focal brain ischemia.

We examined the preventive effect of human recombinant erythropoietin (HrEPO) on nitric oxide (NO)-mediated toxicity to neurons and cysteine protease release into cytoplasm, which is attributed to neuronal death in brain ischemia. Focal cerebral ischemia was induced by permanent occlusion of middle cerebral artery in two sets of rat. The first set was used to monitor NO concentration and cathepsin activity, while the second was used for histological examination with hematoxylin and eosin, and TUNEL staining. A group in both set was administered human recombinant erythropoietin (HrEPO). NO content, cathepsins B and L activity increased significantly in the post-ischemic cerebral tissue (p<0.05). HrEPO treatment reduced NO concentration and cathepsin activity to control level (p>0.05). A significant increase in the number of necrotic and apoptotic neurons was observed in the post-ischemic cerebral cortex (p<0.05). HrEPO treatment was markedly lowered both of these (p<0.05). It is concluded that HrEPO prevents neuronal death by protecting neuronal liposomes from NO-mediated toxicity and suppressing the release of cathepsins.

Spontaneous acute subdural hematoma and chronic epidural hematoma in a child with F XIII deficiency.

Factor XIII (F XIII) deficiency is a rare autosomal recessive congenital disorder that can cause spontaneous subdural or epidural hematomas. Due to its low incidence, F XIII deficiency may well be under-diagnosed. A 7-year-old girl with no history of medical problems presented with progressive headache of 3 days. Cerebral computed tomography (CT) scans revealed a large right acute parietooccipital subdural hematoma with a significant midline shift. After an emergent parietooccipital craniotomy and evacuation of the subdural hematoma, a screening test for factor XIII was performed. The results of the test were abnormal. She had full recovery and was discharged with a follow-up treatment of monthly transfusion of fresh frozen plasma as the replacement and prophylactic therapy. Ten months later, she was referred to our center with headache after a minor head trauma. Her medical history revealed that she had not received fresh frozen plasma for the last 2 months. CT scan showed a chronic right parietal epidural hematoma beneath the craniotomy flap. The present case indicates that although its incidence is very rare, F XIII deficiency can cause acute or chronic subdural and epidural hematomas. Therefore, in acute or chronic subdural and epidural hematomas with no underlying cause, the presence of a potential F XIII deficiency should be suspected as a cause of hemorrhagic diathesis.

Symptomatic foraminal extradural meningeal cyst.

The authors described the case of a 39-year-old man with Klippel-Trénaunay syndrome, who had an extradural meningeal cyst expanding into intervertebral foramen of lumbar 2 and 3 vertebrae. The patient suffered from low back pain radiating to the left lower extremity. Magnetic resonance imaging revealed a huge extradural meningeal cyst growing through intervertebral foramen far laterally. A widened neural foramen of L2 and L3 vertebrae was observed on his plain radiography. The cyst was totally excised after tying the ostium connecting the subarachnoid space of the dural sac. This case supports the congenital theory in the pathogenesis of spinal cysts because the Klippel-Trénaunay syndrome is a congenital disorder including a mesodermal abnormality which may be the causative factor for a congenital defect in dura.

Nitric oxide level and adenosine deaminase activity in cerebrospinal fluid of patients with subarachnoid hemorrhage.

OBJECTIVE: Adenosine and nitric oxide (NO) are known as vasodilatators. We investigated adenosine deaminase (ADA) activity and NO concentration in the cerebrospinal fluid (CSF) of patients with subarachnoid hemorrhage (SAH). METHODS: Forty patients with SAH and 10 controls were included in the study. Nitrate level and ADA activity were measured in CSF. SAH patients were grouped according to the presence of angiographic vasospasm, Hunt and Hess grading, Glasgow Coma Scale (GCS) and Fisher Grade (FG). RESULTS: The level of NO markers in SAH patients decreased when compared to that in the control group (p < 0.05). However, NO markers in patients with vasospasm was higher than in that of patients without vasospasm (p < 0.05). ADA activity increased in patients with SAH (p < 0.01) and also patients with angiographic vasospasm (p < 0.05). ADA activity in the poor-grade SAH group was higher than that in the good-grade SAH group. The group with the lower GCS showed increased ADA activity compared to those with a higher GCS score (p < 0.01). Furthermore, patients with FG 4 had a higher level of ADA activity compared to FG 1 and 2 and FG 3 (p < 0.001 and p < 0.01, respectively). CONCLUSION: Decreased NO level may participate in the early development of vasospasm. However, the increased level of ADA activity in the SAH patients with the poor clinical and consciousness level may have resulted from the ischemic cerebral insult.

[Efficiency of coenzyme Q(10) at experimental spinal cord injury]. / Deneysel spinal kord yaralanmasinda koenzim Q10'un etkinligi.

BACKGROUND: In this study, we aimed to compare the efficacy of methylprednisolone, coenzyme Q(10) and combined methylprednisolone and coenzyme Q(10) treatments on experimental spinal cord injury. METHODS: Thirty-two male Sprague-Dawley rats (200-250 g) were divided into four groups. Spinal cord injury (SCI) was performed by placement of an aneurysm clip, extradurally at the level of T4-5. After the trauma, group K (control group) received soybean oil, group M (methylprednisolone group) received 30 mg.kg-1 methylprednisolone and 5.4 mg.kg.hour-1 maintenance dose of methylprednisolone, group Q (coenzyme Q(10) group) received 10 mg.kg-1 coenzyme Q(10), group MQ (methylprednisolone and coenzyme Q(10) group) received 30 mg.kg-1 methylprednisolone and 5.4 mg.kg.hour-1 maintenance dose of methylprednisolone and 10 mg.kg-1 coenzyme Q(10) intraperitoneally. Twenty-four hours after the trauma spinal cord samples of the rats were obtained and tissue samples had been harvested for both biochemical and histopathological evaluation. RESULTS: In histopathological examination, the edema pattern was significantly more severe in group K than the group M, group Q and group MQ (p<0.001). There was no statistically significant difference between group M, group Q and group MQ regarding edema and bleeding (p>0.05). Mean superoxide dismutase (SOD) scores were significantly low while comparing the group K with all remaining groups and the group MQ comparing with the group M (p<0.05). Mean malondialdehyde (MDA) scores were low in the group M, Q and MQ in comparison with the group K, but there was no statistically significant difference between all groups (p>0.05). CONCLUSION: Methylprednisolone, coenzyme Q(10) and combined methylprednisolone and coenzyme Q(10) treatments were found to be effective as they decrease the edema and coenzyme Q(10) could be effective for prevention of secondary injury at experimental SCI.

Genomic alterations in low-grade, anaplastic astrocytomas and glioblastomas.

To extend our understanding of potential stepwise genetic alterations that may underlie tumor progression from low-grade astrocytomas to glioblastomas, histopathologic and comparative genomic hybridization analyses were performed on tumor specimens from 68 primary lesions, including 40 glioblastomas, 10 anaplastic and 18 low-grade astrocytomas. The number of aberrations per case increased towards the higher grade tumors (grade II: 1.66+/-1.49; grade III: 2.80+/-1.68; grade IV: 3.02+/-1.07; F=6.955, p=0.002). A gain of 7/7q was common and the most frequently seen aberration in low-grade astrocytomas, whereas loss of 10q was the most frequently seen anomaly in anaplastic astrocytomas and glioblastomas. Chromosome 7p amplification was only detected in glioblastomas. Chromosome 10/10q deletion and combination of 1p, 19q and 17p deletions were specific to high-grade astrocytic tumors. Sequences of chromosome 7 and 10 seem to have pivotal roles in the biology of human gliomas. The genomic copy deletions of chromosomes 1p and 19q might provide an alternative mechanism in the genesis of astrocytomas.

An unusual case of cervical clear-cell meningioma in pediatric age.

INTRODUCTION AND BACKGROUND: A 4-year-old girl was admitted with complaints of diplegia, right lower limb monoplegia, and left lower limb monoparesia. Cervical magnetic resonance imaging revealed an intradural-extramedullary tumor at the level of C1-C2. The tumor was resected totally. Histopathologic diagnosis revealed clear-cell meningioma. DISCUSSION: Intraspinal clear-cell meningioma (ICCM) is a rare aggressive variant of meningioma. There are only 25 cases reported to date, and only 13 of them are in pediatric age group. Of these 25 ICCM cases, only two are at cervical region. This report is the first ICCM case at upper cervical region (C1-C2) in both adult and pediatric age populations.

The importance of genomic copy number changes in the prognosis of glioblastoma multiforme.

Glial tumors are the most common tumors of the nervous system, affecting individuals at any age. Since understanding of the molecular pathologies underlying human gliomas is still very poor, the treatment and therefore prognosis of this malignancy could not yet be improved. In order to determine whether different glioblastoma-associated genomic aberrations may serve as prognostic markers in combination with histopathological findings, 20 primary glioblastoma multiforme tumors were screened by comparative genomic hybridization, and the results were compared with histopathological and clinical features. All tumors showed genomic copy aberrations detected by comparative genomic hybridization. Regional and numerical increases in chromosome 7 copy number were the most frequently seen abnormality (10/20 tumors), followed by loss of chromosome 10 (8/20). Both of these aberrations were associated with shorter surveillance time. Chromosome 12q amplification was detected in seven tumors. Loss of 17p, 1p, and 19q in combination was seen in three cases. One of them was a giant cell GBM, whereas the remaining two cases were still alive. Combination of chromosome 1p and 19q deletions was also seen in a case with long surveillance. According to the preliminary findings of this study, in addition to the EGFR gene, amplification of other genes on chromosome 7 and the deletion of PTEN gene and other cancer-related genes on chromosome 10 appeared important to the development of glioblastoma multiforme and were associated with poor prognosis, whereas the combination of chromosome 1p and 19q deletions seems to be an informative molecular marker for better prognosis. The clinical features and genetic alterations of primary and secondary glioblastoma multiforme should be compared in large series to clarify the effective prognostic markers; and further molecular analyses focused on chromosomes 7 and 10 will be very helpful for understanding the molecular mechanisms underlying the progression of glioblastoma.

Detection of chromosomal imbalances in spinal meningiomas by comparative genomic hybridization.

Little is known about genetic mutations during the malignant progression of spinal meningiomas. This study investigated genomic changes across the entire genome in spinal meningioma samples to determine possible mechanism(s) of tumorigenesis. Paraffin-embedded tissue sections of 16 spinal meningiomas were analyzed by the comparative genomic hybridization (CGH) technique. Lymphocytes of the patients were evaluated as controls. Genomic change was detected in 11 samples. Complete or partial loss of chromosome 22 was the most commonly seen abnormality in eight cases. Chromosome losses on 1p, 9p, and 10q and gains on 5p and 17q were the other abnormalities. These changes are all frequently seen in meningiomas, but are mostly specific to atypical and anaplastic meningiomas. However, in the present study, copy number changes on chromosomes 9p (3 samples), 17q (2 samples), and 1p (2 samples) were seen even in the benign tumors. Our results suggest that in addition to the neurofibromatosis type 2 tumor suppressor gene, other cancer-related genes located on 1p, 9p, 10q, and 17q might be involved in the etiology of spinal meningiomas.

Comparative genomic hybridization analysis of genomic alterations in benign, atypical and anaplastic meningiomas.

BACKGROUND: Meningiomas are common tumors of the central nervous system. Although most are benign tumors, approximately 10% show a histologic progression to a higher malignancy grade similar to atypical (GII) and anaplastic (GIII) meningiomas. Monosomy 22q12 is the most frequent genetic alteration detected in these tumors, but failure of detection of 22q mutations in about 40% of tumors which are indistinguishable from meningiomas with 22q deletions with respect to clinical and histopathologic features, makes it apparent that an alternative mechanism is responsible for the initiation of meningioma. Moreover, little is known about genetic alterations during malignant progression of meningioma. PURPOSE: In order to determine the genetic pathways underlying the development of meningioma, 15 benign (WHO grade I), 7 atypical (WHO grade II) and 3 anaplastic (WHO grade III), sporadic meningiomas were screened by Comparative Genomic Hybridization (CGH). RESULTS: Statistical analysis revealed a significant correlation between the number of chromosomal imbalances and the tumor grade; the numbers of total alterations detected per tumor were 2.20 (2.24 for GI, 10.00 (1.17 for GII and 14.66 (1.15 for GIII. The most frequent abnormality seen in benign tumors was loss on 22q (47%). The second alteration was 1p deletion (33%) and this abnormality was also the common aberration in three tumors without CGH detected 22q deletion. In GII, aberrations most commonly identified were losses on 1p (6/7 cases), 22q (5/7 cases), 10q (4/7 cases), 14q and 18q (3/7 cases) as well as gains on 15q and 17q (3/7 cases). In GIII, genomic loss on 1p was the most commonly observed abnormality (3/3). Losses on 9p, 10q, 14q, 15q, 18q and 22q as well as gains on 12q, 15q and 18p were the other genomic alterations detected by CGH. Combined 1p/14q deletions were encountered in 2/15 benign, 3/7 atypical and 2/3 anaplastic meningiomas. By CGH, DNA sequences on 17q21-qter were seen to be amplified in 1/7 GII and 2/3 GIII, whereas highly amplified DNA sequences on 12q13-qter, 20q and 22q11-q12 were seen in one GII, two GII/one GIII, and one GIII, respectively. CONCLUSION: It was concluded that chromosomal deletion from 1p could play a major role in the initiation and progression of meningiomas and that 1p/14q deletions could be a primary focus of further detailed assessment of tumour genesis.