Hasan Emre Aydin

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 grapes 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.

IDH1 mutations is prognostic marker for primary glioblastoma multiforme but MGMT hypermethylation is not prognostic for primary glioblastoma multiforme

PURPOSE To establish the frequency of IDH1 mutations and MGMT methylation in primary glioblastomas. EXPERIMENTAL DESIGN We screened primary glioblastoma multiforme (GBM) in a population-based study for IDH1 mutations and MGMT methylation and correlated them with clinical data. RESULTS IDH1 mutations were detected in 5 of 40 primary glioblastomas (12,5%). Primary GBM patients carrying IDH1 mutations were significantly younger, mean age of 41±5.06years, than patients with wild-type IDH1, mean age of 57±2,29years, p=0.011. The mean survival time of all GBM patients with and without IDH1 mutations was 19months (5 cases) and 16months (35 cases), respectively (p>0,05). MGMT methylation was detected in 13 of the 40 patients (32,5%). MGMT-promoter methylation did not correlate with overall survival (OS; p>0,05). CONCLUSION In summary, our study is the first study to investigate the IDH1 mutation status and MGMT methylation in primary GBMs in Turkish population and confirmed IDH1 mutation as a genetic marker for also primary GBMs. Our data are still insufficient for definite ascertainment; and our preliminary results suggest: IDH1 status shows an association with younger age and there is a lack of association between IDH1 mutation and survival time. Furthermore MGMT promoter methylation had no prognostic value and lower frequency in primary glioblastomas.

Use of Dural Graft to Prevent Cerebrospinal Fluid (CSF) Leakage and its Effects on Medulla Spinalis: An Experimental Study

Introduction: Dural injuries are encountered generally as trauma, spinal tumor excision or postop complications. It is a major problem leads to cerebrospinal fluid leakage meningitis. The method used often in repair is applying the watertight suture to the damaged area with appropriate measures of fascia and dural grafts. The used grafts can be ranged as bovine pericardium, synthetic collagen matrices, fibrin tissue adhesive, vicryl, and polydioxanone graft. In the studies, it is observed that there is still no significant difference between grafts and fascia. Material-Methods: In our study, 60 Spraque Dawley rats whose weights are ranging from 200-250 gr were used. The solution consists of the ketamine hydrochloride (60 mg/kg) and xylazine (12 mg/kg) was injected intraperitoneally to the subjects and the subjects were taken into anesthesia. The subjects were divided into 5 groups. In the first group no extra action was taken, in the second group, fibrin tissue adhesive was applied on the dural injury and in the third group collagen matrix was applied on the dural injury, in the fourth group bovine pericardium was applied on the dural injury, in the fifth group subcutaneous fascia (autogenetic graft) was applied on the dural injury. Surgical Operation: After providing the sterile conditions and operating the anesthesia agents, the experimental animals were laid down on the operating table in the prone position for surgical operation. Following the local area cleaning and environment isolation, subcutaneous incision was applied. Fascia was opened and paravertebral muscles were scarred subperiostally. After applying L1-4 laminectomy, approximately 2 cm linear incision was made with bistoury and cerebrospinal fluid leakage was observed from the dural injury. Analgesia was applied with 10 mg/kg paracetamol on the subjects which survived approximately 6 weeks after the operation. On the 7th day (early group) after the operation, 6 animals from each group and 6 animals from each group after 6 weeks from the operation were injected 100 mg/kg phenobarbital intraperitoneally and scarification operation was completed. Former incision was opened and spinal cord under the laminectomy area was removed with the dural graft as a block and histopathological findings was provided. Histopathological findings: The incisions from this area were stained with Hematoxylin Eosin and Masson Trichrome. In the examination, collagen, vascular diagenesis and necrosis from histopathological findings were examined in early period (first week) and late period (sixth) week. It was observed that in the groups.

Neuroprotective Effect of Genistein In Peripheral Nerve Injury.

AIM To investigate the effects of genistein in a rat model of sciatic nerve crush injury and complete sciatic nerve transection. The effects of genistein were compared with those of gabapentin, which is widely used in clinical practice for peripheral nerve injury. MATERIAL AND METHODS Forty-eight rats were randomly divided into six groups (8 rats in each group): group 1 (sham); group 2, sciatic nerve crush injury (control); group 3, sciatic nerve crush injury+genistein 20 mg/kg; group 4, sciatic nerve crush injury+gabapentin 90 mg/kg; group 5, sciatic nerve transection+genistein 20 mg/kg; group 6, sciatic nerve transection+gabapentin 90 mg/kg. The effects of genistein and gabapentin were assessed with immunohistochemical staining for growth associated protein-43 (GAP-43) and myelin basic protein (MBP). Interleukin-1β and tumor necrosis factor α levels in the injured nerve specimens were assessed as a measure of inflammatory response; walking track analysis and sciatic function index for neurological recovery and the paw mechanical withdrawal threshold were examined for neuropathic pain. RESULTS On histopathological examination, genistein use was associated with a greater immunoreactivity for GAP-43 and MBP compared with that associated with gabapentin. Genistein and gabapentin had similar effects on anti-inflammatory activity, functional recovery, and neuropathic pain. CONCLUSION Genistein and gabapentin exhibit positive effects on histopathology, inflammation, and clinical findings of peripheral nerve injury. When the systemic side effects of gabapentin are considered, genistein (a basic soy isoflavone that has no side effects) can be used as an alternative to medical treatment in peripheral nerve injury.

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.

RARβ gene methylation is a candidate for primary glioblastoma treatment planning

BACKGROUND We screened RARβ methylation in primary glioblastoma multiforme (GBM) and the results were evaluated based on the clinical data and treatment type. OBJECTIVE The objective of this study was to find new areas for the usage of MS-HRM applications in the determination of methylation levels in primary GBM samples and it shows the association of RARβ methylation with the clinical outcome. METHODS In our study, tumor samples were collected during surgical resection by the Department of Neurosurgery. The clinical and radiologic data was carefully reviewed, compared, and evaluated with the histological results. The methylation status of RARβ was determined by using MS-HRM. RESULTS RARβ gene methylation was detected in 24 out of 40 cases (60%), with different quantitative methylation levels. The mean survival time was 19 months form ethylated cases and 15 months for the non-methylated cases. The survival time of the patients who received treatment was 25 months and the survival time of the patients who received radiotherapy alone or where no treatment protocol applied was 15-20 months. Therefore, a significant difference in survival rates has been observed (P<0.05). This study indicates a potential prognostic value for GBM treatment planning. CONCLUSION Our study is the first study to investigate RARβ methylation in primary GBMs. We conclude that the RARβ gene could be a new prognostic and predictive candidate marker to designate the treatment protocol for primary GBMs.

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.

Effects of resveratrol on inflammation and apoptosis after experimental spinal cord injury

AIM To determine the effects of resveratrol on inflammation and apoptosis after experimental spinal cord injury (SCI). MATERIAL AND METHODS Eighteen Sprague-Dawley rats were randomly divided into three groups. All groups underwent thoracic laminectomy. The first group received no other intervention. The second and third groups suffered SCI via the aneurysm clip compression method, and additionally the third group received resveratrol. After euthanizing the rats, immunohistochemical analysis and biochemical parameters of tumor necrosis factor alpha (TNF-?) and interleukin (IL)-1? were measured. RESULTS The resveratrol group had statistically significant lower levels of TNF-?, IL -1?, and terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling (TUNEL) positive cells and higher number of glial and motor neuron cells. CONCLUSION Resveratrol proves to have remarkable neuroprotective effects on SCI in an experimental model in addition to its proven cardioprotective effects.

Effects of Quercetin and Mannitol on Erythropoietin Levels in Rats Following Acute Severe Traumatic Brain Injury

Objective The aim of this study to investigate the normal values of erythropoietin (EPO) and neuroprotective effects of quercetin and mannitol on EPO and hematocrit levels after acute severe traumatic brain injury (TBI) in rat model. Methods A weight-drop impact acceleration model of TBI was used on 40 male Wistar rats. The animals were divided into sham (group I), TBI (group II), TBI+quercetin (50 mg/kg intravenously) (group III), and TBI+mannitol (1 mg/kg intravenously) (group IV) groups. The malondialdehyde, glutathione peroxidase, catalase, EPO, and hematocrit levels were measured 1 and 4 hour after injury. Two-way repeated measures analysis of variance and Tukey’s test were used for statistical analysis. Results The malondialdehyde levels decreased significantly after administration of quercetin and mannitol compared with those in group II. Catalase and glutathione peroxidase levels increased significantly in groups III and IV. Serum EPO levels decreased significantly after mannitol but not after quercetin administration. Serum hematocrit levels did not change significantly after quercetin and mannitol administration 1 hour after trauma. However, mannitol administration decreased serum hematocrit levels significantly after 4 hour. Conclusion This study suggests that quercetin may be a good alternative treatment for TBI, as it did not decrease the EPO levels.

Comparison of the effects and mechanism of the Curcumin with different acting drugs in Experimental Vasospasm after Subarachnoid Hemorrhage.

AIM Cerebral vasospasm following subarachnoid hemorrhage (SAH) is the most important complication that effects the mortality and morbidity of patients with intracranial aneurysm. Today, the mechanisms of vasospasm are not understood in spite of experimental and clinical researches. The aim of our study was to investigate the effects of curcumin on vasospasm following SAH. MATERIAL AND METHODS In this study, 64 rats (200-250 g weight) were divided into 7 groups. Group 1: having no treatment after SAH; Group 2: treatment with nimodipine after SAH; Group 3: treatment with nicorandil after SAH; Group 4: treatment with sildenafil citrate after SAH; Group 5: treatment with 150 mg/kg curcumin after SAH; Group 6: treatment with 300 mg/kg curcumin after SAH, Group 7: treatment with 600 mg/kg curcumin after SAH. The experimental SAH was induced by injection of autologous blood into the cisterna magna. After medical treatment, in the first hour, blood was taken for quantified the levels of TNF-α, IL-1β and IL-6. Then, cerebrum and cerebellum were removed for analysis. Basilar artery luminal diameter was measured and apoptotic cell count was performed with tissue samples. RESULTS Histopathological findings showed that, in sufficient dose, curcumin dilated the basilar artery beside anti-oxidant effect. CONCLUSION Curcumin can be used for the treatment of vasospasm as a new medical drug.