Berrin İmge Ergüder

The protective effect of low-dose methotrexate on ischemia-reperfusion injury of the rabbit spinal cord.

Methotrexate was developed as a cytostatic agent, but at low doses, it has shown potent anti-inflammatory activity. Previous studies have demonstrated that the anti-inflammatory effects of methotrexate are primarily mediated by the release of adenosine. In this study, we hypothesized that low-dose methotrexate has protective effects in spinal cord ischemia-reperfusion injury. Rabbits were randomized into the following four groups of eight animals each: group 1 (control), group 2 (ischemia), group 3 (methylprednisolone) and group 4 (methotrexate). In the control group only a laparotomy was performed. In all the other groups, the spinal cord ischemia model was created by the occlusion of the aorta just caudal to the renal artery. Neurological evaluation was performed with the Tarlov scoring system. Levels of myeloperoxidase, malondialdehyde and catalase were analyzed, as were the activities of xanthine oxidase and caspase-3. Histopathological and ultrastructural evaluations were also performed. After ischemia-reperfusion injury, increases were found in the serum and tissue myeloperoxidase levels, tissue malondialdehyde levels, xanthine oxidase activity and caspase-3 activity. In contrast, both serum and tissue catalase levels were decreased. After the administration of a low-dose of methotrexate, decreases were observed in the serum and tissue myeloperoxidase levels, tissue malondialdehyde levels, xanthine oxidase activity and caspase-3 activity. In contrast, both the serum and tissue catalase levels were increased. Furthermore, low-dose methotrexate treatment showed improved results concerning the histopathological scores, the ultrastructural score and the Tarlov scores. Our results revealed that low-dose methotrexate exhibits meaningful neuroprotective activity following ischemia-reperfusion injury of the spinal cord.

Neuroprotective effects of testosterone on ischemia/reperfusion injury of the rabbit spinal cord.

AIM Previous studies demonstrated the neuroprotective effects of testosterone, but no previous study has examined the neuroprotective effects of testosterone on spinal cord ischemia/reperfusion injury. The purpose of this study was to evaluate whether testosterone could protect the spinal cord from ischemia/reperfusion injury. METHODS Rabbits were randomised into four groups of eight animals as follows: group 1 (control), group 2 (ischemia), group 3 (methylprednisolone) and group 4 (testosterone). In the control group only a laparotomy was performed. In all other groups, the spinal cord ischemia model was created by the occlusion of the aorta just caudal to the renal artery. Levels of malondialdehyde and catalase were analysed, as were the activities of caspase-3, myeloperoxidase, and xanthine oxidase. Histopathological and ultrastructural evaluations were performed. Neurological evaluation was performed with the Tarlov scoring system. RESULTS After ischemia-reperfusion injury, increases were found in caspase-3 activity, myeloperoxidase activity, malondialdehyde levels, and xanthine oxidase activity. In contrast, decreases in catalase levels were observed. After the administration of testosterone, decreases were observed in caspase-3 activity, myeloperoxidase activity, malondialdehyde levels, and xanthine oxidase activity, whereas catalase levels increased. Furthermore, testosterone treatment showed improved results concerning histopathological scores, ultrastructural score and Tarlov scores. CONCLUSIONS Our results revealed for the first time that testosterone exhibits meaningful neuroprotective activity following ischemia-reperfusion injury of the spinal cord.

Antioxidant and antiapoptotic effects of darbepoetin-α against traumatic brain injury in rats.

Introduction In this study, we tried to determine whether darbepoetin-α would protect the brain from oxidative stress and apoptosis in a rat traumatic brain injury model. Material and methods The animals were randomized into four groups; group 1 (sham), group 2 (trauma), group 3 (darbepoetin α), group 4 (methylprednisolone). In the sham group only the skin incision was performed. In all the other groups, a moderate traumatic brain injury modelwas applied. Results Following trauma both glutathione peroxidase, superoxide dismutase levels decreased (p < 0.001 for both); darbepoetin-α increased the activity of both antioxidant enzymes (p = 0.001 and p < 0.001 respectively). Trauma caused significant elevation in the nitric oxide synthetase and xanthine oxidase levels (p < 0.001 for both). Administration of darbepoetin-α significantly decreased the levels of nitric oxide synthetase and xanthine oxidase (p < 0.001 for both). Also, trauma caused significant elevation in the nitric oxide levels (p < 0.001); darbepoetin-α administration caused statistically significant reduction in the nitric oxide levels (p < 0.001). On the other hand, malondialdehyde levels were increased following trauma (p < 0.001), and darbepoetin α significantly reduced the malondialdehyde levels (p < 0.001). Due to the elevated apoptotic activity following the injury, caspase-3 activity increased significantly. Darbepoetin-α treatment significantly inhibited apoptosis by lowering the caspase-3 activity (p < 0.001). In the darbepoetin group, histopathological score was lower than the trauma group (p = 0.016). Conclusions In this study, darbepoetin-α was shown to be at least as effective as methylprednisolone in protecting brain from oxidative stress, lipid peroxidation and apoptosis.

Does Decorin Protect Neuronal Tissue via Its Antioxidant and Antiinflammatory Activity from Traumatic Brain Injury: An Experimental Study.

BACKGROUND The development of secondary brain injury via oxidative stress after traumatic brain injury (TBI) is well known. Decorin (DC) inactivates transforming growth factor β1, complement system, and tumor necrosis factor α, which are related to oxidative stress and apoptosis. Consequently, the aim of the present study was to evaluate the role of DC on TBI. METHODS A total of 24 male rats were used and divided into 4 groups as follows; control, trauma, DC, and methylprednisolone (MP). The trauma, DC, and MP groups were subjected to closed-head contusive weight-drop injuries. Rats received treatment with intraperitoneal saline, DC, or MP, respectively. All the animals were killed at the 24th hour after trauma and brain tissues were extracted. The oxidant/antioxidant parameters (malondialdehyde, glutathione peroxidase, superoxide dismutase, and NO) and caspase 3 in the cerebral tissue were analyzed, and histomorphologic evaluation of the cerebral tissue was performed. RESULTS Levels of malondialdehyde, NO, and activity of caspase 3 were significantly reduced, and in addition glutathione peroxidase and superoxide dismutase levels were increased in the DC and MP groups compared with the trauma group. The pathology scores and the percentage of degenerated neurons were statistically lower in the DC and MP groups than in the trauma group. CONCLUSIONS The results of the present study showed that DC inactivates transforming growth factor β1 and protects the brain tissue and neuronal cells after TBI.

Potential neuroprotective effect of Anakinra in spinal cord injury in an in vivo experimental animal model

Objective: To evaluate the therapeutic effects of inhibiting interleukin-1 beta (IL-1β) in vivo using Anakinra in an experimental model of spinal cord injury (SCI). Methods: All experimental procedures were performed in the animal laboratory of Ankara Education and Research Hospital, Ankara, Turkey between August 2012 and May 2014. The SCI was induced by applying vascular clips to the dura via a 4-level T5-T8 laminectomy. Fifty-four rats were randomized into the following groups: controls (n = 18), SCI + saline (n = 18), and SCI + Anakinra (n = 18). Spinal cord samples were obtained from animals in both SCI groups at one, 6, and 24 hours after surgery (n = 6 for each time point). Spinal cord tissue and serum were extracted, and the levels of IL-1β, malondialdehyde, glutathione peroxidase, superoxide dismutase, and catalase were analyzed. Furthermore, histopathological evaluation of the tissues was performed. Results: The SCI in rats caused severe injury characterized by edema, neutrophil infiltration, and cytokine production followed by recruitment of other inflammatory cells, lipid peroxidation, and increased oxidative stress. After SCI, tissue and serum IL-1β levels were significantly increased, but were significantly decreased by Anakinra administration. Following trauma, glutathione peroxidase, superoxide dismutase, and catalase levels were decreased; however, Anakinra increased the activity of these antioxidant enzymes. Malondialdehyde levels were increased after trauma, but were unaffected by Anakinra. Histopathological analysis showed that Anakinra effectively protected the spinal cord tissue from injury. Conclusion: Treatment with Anakinra reduces inflammation and other tissue injury events associated with SCI.

The Protective effect of Omeprazole Against Traumatic Brain Injury: An Experimental Study

BACKGROUND The development of secondary brain injury via oxidative stress after traumatic brain injury (TBI) is a well-known entity. Consequently, the aim of the present study was to evaluate the role of omeprazole (OM) on rat model of TBI. METHODS A total of 24 male rats were used and divided into 4 groups as follows; control, trauma, OM, and methylprednisolone (MP). The trauma, OM, and MP groups were subjected to closed-head contusive weight-drop injuries. Rats received treatment with saline, OM, or MP, respectively. All the animals were sacrificed at 24 hours after trauma and brain tissues were extracted. The oxidant/antioxidant parameters (malondialdehyde, glutathione peroxidase, superoxide dismutase, nitric oxide) and caspase-3 in the cerebral tissue were analyzed, and histomorphologic evaluation of the cerebral tissue was performed. RESULTS Levels of MDA and activity of caspase-3 were significantly reduced in the OM and MP groups compared with the trauma group. Glutathione peroxidase and superoxide dismutase levels were increased both in the OM and MP groups compared with the trauma group. The pathology scores were statistically lower in the OM and MP groups than the trauma group. CONCLUSIONS The results of the present study showed that OM was as effective as MP in protecting brain from oxidative stress, and apoptosis in the early phase of TBI.

Comparative effects of methylprednisolone and tetracosactide (ACTH 1–24 ) on ischemia/reperfusion injury of the rabbit spinal cord

Introduction Tetracosactide is an engineered peptide that applies the same biological impacts as the endogenous adrenocorticotropic hormone. Previous studies indicated that tetracosactide has anti-inflammatory, antioxidant and neurotrophic activity. In this study, we hypothesized that tetracosactide may have protective effects in spinal cord ischemia-reperfusion injury. Material and methods Rabbits were randomized into the accompanying four groups of eight animals each: group 1 (control), group 2 (ischemia), group 3 (methylprednisolone) and group 4 (tetracosactide). In the control group, just a laparotomy was performed. In the various groups, the spinal cord ischemia model was made by the impediment of the aorta only caudal to the renal vein. Neurological assessment was conducted with the Tarlov scoring system. Levels of myeloperoxidase, malondialdehyde and catalase were analyzed, similar to the activities of xanthine oxidase and caspase-3. Histopathological and ultrastructural assessments were additionally performed. Results After ischemia-reperfusion injury, increments were found in the tissue myeloperoxidase levels (p < 0.001), malondialdehyde levels (p < 0.001), xanthine oxidase action (p < 0.001) and caspase-3 movement (p < 0.001). Conversely, both serum and tissue catalase levels were diminished (p < 0.001 for both). After the administration of tetracosactide, declines were seen in the tissue myeloperoxidase levels (p < 0.001), malondialdehyde levels (p = 0.003), xanthine oxidase action (p < 0.001) and caspase-3 movement (p < 0.001). Conversely, both the serum and tissue catalase levels were expanded (p < 0.001). Besides, tetracosactide treatment indicated enhanced results related to the histopathological scores (p < 0.001), the ultra-structural score (p = 0.008) and the Tarlov scores (p < 0.001). Conclusions The findings showed for the first time that tetracosactide shows significant neuroprotective activity against ischemia-reperfusion injury of the spinal cord.

Follicular fluid norepinephrine and dopamine concentrations are higher in polycystic ovary syndrome

Abstract The aim of the present study was to compare follicular fluid (FF) levels of norepinephrine (NE) and dopamine (DA) in polycystic ovary syndrome (PCOS) and non-PCOS patients who underwent in vitro fertilization (IVF). Forty-seven PCOS patients (study group) and 61 patients with male factor infertility (control group) who underwent IVF using GnRH agonist protocol were recruited. Concentrations of NE and DA were measured in FF specimens of all patients. Demographic characteristics were comparable between the groups. Significantly higher levels of NE were measured in FF of PCOS patients (median: 61.05 nmol/l) compared to those with male infertility (median: 49.82 nmol/l). Similarly, significantly higher levels of DA were measured in FF of PCOS patients (median: 23.70 nmol/l) compared to those with male infertility (median: 18.28 nmol/l). In conclusion, the FF concentrations of both catecholamine are increased in PCOS patients when compared to non-PCOS patients.