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Yayın Assessment of the neuroprotective effects of the acetylcholinesterase inhibitor huperzine A in an experimental spinal cord trauma model(EDIZIONI MINERVA MEDICA, 2018) Antar, Veysel; Baran, Oguz; Yuceli, Sahin; Erdogan, Hakan; Altintas, Ozge; Baran, Gozde E.; Tasdemiroglu, ErolBACKGROUND: Spinal cord injury is nowadays still a challenging disease, and a treatment option aimed at the primary site of injury does not currently exist. Therefore, the management of acute spinal cord injury has recently focused on the reasons behind the aggravation of the initial insult through secondary mechanisms, and the search for pharmacological treatment protocols is generally aimed at reducing and minimizing the neural injury and neurological sequela. The secondary spinal cord injury usually develops following a primary lesion induced by spinal cord contusion and the emergence of apoptotic cells has been found to play an important role in the development of secondary injury. We propose that huperzine A may induce a significant reduction in the number of apoptotic cells because it possesses the ability to protect cells against glutamate, ischemia and staurosporine-induced cytotocity and apoptosis. METHODS: Huperzine A was administered intraperitoneally to male Wistar Albino rats (220-340 g of body weight) after moderate static clip compression (70 g for 60 s) of the spinal cord at T7 level. Neurological functions were assessed using the Basso-Beattle-Breshanan (BBB) motor rating scale until 3th and 7th days before perfusion, following which the spinal cord was harvested for histopathological examinations and apoptotic cell counts. RESULTS: Histopathological evaluations of the spinal cord of the control, trauma and huperzine A treated groups were evaluated. Control group showed normal neuronal and vascular structures of the spinal cord. However, in both trauma groups 3rd- and 7th-day perfusion showed extensive cavitation and hemorrhage, areas of necrosis and edema in gray. matter, and degeneration in motor neurons along with patchy areas of necrotic and apoptotic cells. In the group treated with huperzine A, an increased number of normal cells was observed, along with a lower number of necrotic cells, with a significant reduction in the apoptotic cells (P<0.01). The administration of huperzine A improved post-trauma motor performance. Furthermore, BBB scores of all groups showed that there was an improvement of locomotor abilities in the treatment group as compared with the control. CONCLUSIONS: When compared with controls, huperzine A treatment demonstrates a significant reduction in the number of apoptotic cells. In addition, the group treated with huperzine A showed significant and appreciable neurological improvement in rats.Yayın The Effects of Difumarate Salt S-15176 after Spinal Cord Injury in Rats(KOREAN NEUROSURGICAL SOC, 2015) Erdogan, Hakan; Tuncdemir, Matem; Kelten, Bilal; Akdemir, Osman; Karaoglan, Alper; Tasdemiroglu, ErolObjective : In the present study we analyzed neuroprotective and antiapoptotic effect of the difumarate salt S-15176, as an anti-ischemic, an antioxidant and a stabilizer of mitochondrial membrane in secondary damage following spinal cord injury (SCI) in a rat model. Methods : Three groups were performed with 30 Wistar rats; control (1), trauma (2), and a trauma+S-15176 (10 mg/kg i.p., dimethyl sulfoxide) treatment (3). SCI was performed at the thoracic level using the weight-drop technique. Spinal cord tissues were collected following intracardiac perfusion in 3rd and 7th days of posttrauma. Hematoxylin and eosin staining for histopatology, terminal deoxynucleotidyl transferase dUTP nick end labeling assay for apoptotic cells and immunohistochemistry for proapoptotic cytochrome-c, Bax and caspase 9 were performed to all groups. Functional recovery test were applied to each group in 3rd and 7th days following SCI. Results : In trauma group, edematous regions, diffuse hemorrhage, necrosis, leukocyte infiltration and severe degeneration in motor neurons were observed prominently in gray matter. The number of apoptotic cells was significantly higher (p<0.05) than control group. In the S-15176-treated groups, apoptotic cell number in 3rd and 7th days (p<0.001), also cytochrome-c (p<0.001), Box (p<0.001) and caspase 9 immunoreactive cells (p<0.001) were significantly decreased in number compared to trauma groups. Hemorrhage and edema in the focal areas were also noticed in gray matter of treatment groups. Results of the locomotor test were significantly increased in treatment group (p<0.05) when compared to trauma groups. Conclusion : We suggest that difumarate salt S-15176 prevents mitochondrial pathways of apoptosis and protects spinal cord from secondary injury and helps to preserve motor function following SCI in rats.Yayın Searching Evidences of Stroke in Animal Models: A Review of Discrepancies(TURKISH NEUROSURGICAL SOC, 2017) Kaya, Ahmet Hilmi; Erdogan, Hakan; Tasdemiroglu, ErolSo far, animal models have helped us better understand the pathophysiology of the ischemic brain damage but they could not contribute so much to clinical practice. The discrepancies in results regarding neuroprotective agents in animal experiments compared to clinical trials have not been solved. Various animal models of ischemic stroke have proven efficacy of many neuroprotective agents without any considerable result in phase III clinical trials. As is well known, stroke-related focal cerebral ischemia or cardiac arrest related global cerebral ischemia are major causes of disability and death among human subjects. Animal models are essential to evaluate the therapeutic approaches for humans. In this review, we will try to answer two important questions: 1) Which factors endanger the reliability of experimental studies of stroke on animal models? 2) How can we design our experiments to reflect the neurorestoration and/or neuroprotection mechanisms following ischemic injury, when it comes to human disease?Yayın Tumor-to-Tumor Metastasis of the Central Nervous System(TURKISH NEUROSURGICAL SOC, 2014) Erdogan, Hakan; Aydin, Mehmet Volkan; Tasdemiroglu, ErolTumor-to-tumor metastasis is a well recognized phenomenon. Although any tumor may be potential recipient of metastasis, renal cell carcinoma and meningioma are the most common malignant and benign recipients, respectively, whereas the lung and breast are the most common metastatic donors respectively, in both settings. Patients with hereditary cancer syndromes may be at higher risk for the development of tumor-to-tumor metastases. The most common pattern of tumor-to-tumor metastasis for intracranial neoplasms is the type in which an aggressive high-grade malignancy serves as the source of tumor and a more indolent neoplasm serves as the recipient tumor. The development of tumor metastasis from a second primary malignancy is uncommon and remains biologically puzzling. Its low incidence has made its full biological characterization evasive. Although rare, neurosurgeons should be aware of the entity of tumor-to-tumor metastasis.
