Guven Erbil

Neuroprotective effects of resveratrol against traumatic brain injury in immature rats

Childhood trauma resulting in traumatic brain injury (TBI) due to accidents and abuse is the major cause of death and dysfunction in the young. Since there are no approved specific pharmacological agents that block the progression of the secondary injury, the current management of TBI is mainly supportive. We aimed to determine the effect of resveratrol on hippocampal damage and behavioral deficits in 7-day-old rat pups subjected to contusion injury. Resveratrol was injected intraperitoneally at the doses of 100 mg/kg of body weight immediately after induction of traumatic injury. Hippocampal damage was examined by cresyl violet staining and behavioral alterations were evaluated using open field and novel object recognition tests 2 weeks after trauma. Histopathological evaluation showed that treatment with a single dose of 100 mg/kg resveratrol (i.p.) after the trauma significantly ameliorated the trauma induced hippocampal neuron loss at ipsilateral and contralateral hippocampal brain regions of rats. Additionally, treatment with resveratrol decreased anxiety and increased cortex/hippocampus dependent memory of animals subjected to blunt head trauma. These results show that acute treatment of resveratrol has a neuroprotective role against trauma induced hippocampal neuron loss and associated cognitive impairment in rats.

The effects of selenium against cerebral ischemia-reperfusion injury in rats

It is known that the brain tissue is extremely sensitive to ischemia-reperfusion (IR) injury and therefore, brain ischemia and consecutive reperfusion result in neural damage and apoptosis. The proinflammatory cytokines such as tumor necrosis factor alfa (TNF-alpha) and interleukin-1 beta (IL-1beta) are produced during neurological disorders including cerebral ischemia. On the other hand, nerve growth factor (NGF), which is essential for the differentiation, survival and functions of neuronal cells in the central nervous system, regulate neuronal development through cell survival and cell death signaling. In the present study, we aimed to investigate the effect of selenium (Se) on prefrontal cortex and hippocampal damage in rats subjected to cerebral IR injury. Selenium was injected intraperitoneally at the doses of 0.625 mg/(kg day) after induction of IR injury. Prefrontal cortex and hippocampal damage was examined by cresyl-violet staining. Apostain and caspase-3 immune staining were used to detect apoptosis. TNF-alpha, IL-1beta and NGF levels were also evaluated. Histopathological evaluation showed that treatment with selenium after ischemia significantly attenuated IR-induced neuronal death in prefrontal cortex and hippocampal CA1 regions of rats. Apoptotic cells stained with apostain and caspase-3 were significantly decreased in treatment group when compared with the IR group. Additionally, treatment with selenium decreased the TNF-alpha and IL-1beta levels and increased the NGF levels in prefrontal cortex and hippocampal tissue of animals subjected to IR. The present results suggest that selenium is potentially a beneficial agent in treating IR-induced brain injury in rats.

Protective effect of erythropoietin pretreatment in testicular ischemia-reperfusion injury in rats

BACKGROUND/PURPOSE This study was designed to investigate the effects of recombinant erythropoietin (EPO), a hormone widely used for treatment of uremic anemia, in rats subjected to testicular ischemia and reperfusion (I/R). METHODS Thirty-five male rats were divided into the following: control, sham operated, ischemia (I), I/R, and I/R + EPO groups. In the I group, 2 hours of left unilateral testicular torsion were performed, and in the I/R and I/R + EPO groups, an additional 2 hours of testicular detorsions were performed. The I/R + EPO group was pretreated intraperitoneally with EPO (500 IU/kg) before reperfusion. Testicular tissue samples were examined for biochemical and histopathologic parameters. Apoptotic cells in all testes were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling technique and caspase 3 immunohistochemistry. RESULTS At histopathologic examination, ischemic changes in primary spermatocytes were noted in all torted testes. Cellular damage and apoptosis were more severe in ischemic groups than the EPO-pretreated group. There were statistically significant differences in tissue biochemical parameters in the I and I/R groups compared with the I/R + EPO group. CONCLUSIONS The results of the present study suggest that EPO exerts protective effects against I/R injury via the modulation of free radical scavengers activities, which decreases lipid peroxidation levels and attenuation of apoptosis.

The Effects of α-Lipoic Acid against Testicular Ischemia-Reperfusion Injury in Rats

Testicular torsion is one of the urologic emergencies occurring frequently in neonatal and adolescent period. Testis is sensitive to ischemia-reperfusion injury, and, therefore, ischemia and consecutive reperfusion cause an enhanced formation of reactive oxygen species that result in testicular cell damage and apoptosis. α-lipoic acid is a free radical scavenger and a biological antioxidant. It is widely used in the prevention of oxidative stress and cellular damage. We aimed to investigate the protective effect of α-lipoic acid on testicular damage in rats subjected to testicular ischemia-reperfusion injury. 35 rats were randomly divided into 5 groups: control, sham operated, ischemia, ischemia-reperfusion, and ischemia-reperfusion +lipoic acid groups, 2 h torsion and 2 h detorsion of the testis were performed. Testicular cell damage was examined by H-E staining. TUNEL and active caspase-3 immunostaining were used to detect germ cell apoptosis. GPx , SOD activity, and MDA levels were evaluated. Histological evaluation showed that α-lipoic acid pretreatment reduced testicular cell damage and decreased TUNEL and caspase-3-positive cells. Additionally, α-lipoic acid administration decreased the GPx and SOD activity and increased the MDA levels. The present results suggest that LA is a potentially beneficial agent in protecting testicular I/R in rats.

CARNOSINE ATTENUATES OXIDATIVE STRESS AND APOPTOSIS IN TRANSIENT CEREBRAL ISCHEMIA IN RATS

Cerebral ischemia leads to cognitive decline and neuronal damage in the hippocampus. Reactive oxygen species (ROS) play an important role in the neuronal loss after cerebral ischemia and reperfusion injury. Carnosine has both antioxidant and neuroprotective effects against ROS. In the present study, the effects of carnosine on oxidative stress, apoptotic neuronal cell death and spatial memory following transient cerebral ischemia in rats were investigated. Transient ischemia was induced by occlusion of right common carotid artery of rats for 30 min and reperfusion for 24 h or 1 week. Rats received intraperitoneal injection of 250 mg/kg carnosine or saline 30 min prior to experiment. Determination of antioxidant enzyme activities was performed spectrophotometrically. To detect apoptotic cells, TUNEL staining was performed using an In Situ Cell Death Detection Kit. Carnosine treatment elicited a significant decrease in lipid peroxidation and increase in antioxidant enzyme activities in ischemic rat brains. The number of TUNEL-positive cells was decreased significantly in carnosine-treated group when compared with the ischemia-induction group. Carnosine treatment did not provide significant protection from ischemia induced deficits in spatial learning. The results show that carnosine is effective as a prophylactic treatment for brain tissue when it is administered before ischemia without affecting spatial memory.

Autologous rabbit adipose tissue-derived mesenchymal stromal cells for the treatment of bone injuries with distraction osteogenesis

BACKGROUND AIMS Adipose tissue-derived mesenchymal stromal cells (MSCs) have a higher capacity for proliferation and differentiation compared with other cell lineages. Although distraction osteogenesis is the most important therapy for treating bone defects, this treatment is restricted in many situations. The aim of this study was to examine the therapeutic potential of adipose tissue-derived MSCs and osteoblasts differentiated from adipose tissue-derived MSCs in the treatment of bone defects. METHODS Bone defects were produced in the tibias of New Zealand rabbits that had previously undergone adipose tissue extraction. Tibial osteotomy was performed, and a distractor was placed on the right leg of the rabbits. The rabbits were placed in control (group I), stem cell (group II) and osteoblast-differentiated stem cell (group III) treatment groups. The rabbits were sacrificed, and the defect area was evaluated by radiologic, biomechanical and histopathologic tests to examine the therapeutic effects of adipose tissue-derived MSCs. RESULTS Radiologic analyses revealed that callus density and the ossification rate increased in group III compared with group I and group II. In biomechanical tests, the highest ossification rate was observed in group III. Histopathologic studies showed that the quality of newly formed bone and the number of cells active in bone formation were significantly higher in group III rabbits compared with group I and group II rabbits. CONCLUSIONS These data reveal that osteoblasts differentiated from adipose tissue-derived MSCs shorten the consolidation period of distraction osteogenesis. Stem cells could be used as an effective treatment for bone defects.

Effects of Ginkgo biloba on airway histology in a mouse model of chronic asthma.

Platelet-activating factor (PAF) is an inflammatory mediator involved in the pathophysiology of asthma, suggesting a therapy antagonizing its effects may play a role in the disease treatment. The aim of the study was to determine the effects of Ginkgo biloba, a PAF antagonist, on lung histology. Thirty-five BALB/c mice were divided into five groups; A, B, C, D, and the control. All mice except controls were sensitized and challenged with ovalbumin. Mice in group A (placebo) received saline; group B received G. biloba, 100 mg/kg; group C received G. biloba, 150 mg/kg; and group D received dexamethasone, 1 mg/kg via orogastric gavage for 7 consecutive days. Chronic structural changes and airway remodeling were evaluated by using light and electron microscopy in all groups. Evaluation of lung histology indicated that the number of goblet cells, mast cells, thicknesses of epithelium, and basement membrane were significantly improved in groups B and C when compared with group A. There was no statistically significant difference in thicknesses of subepithelial smooth muscle between groups A, B, and C. When doses of G. biloba were compared with each other, only the number of goblet cells was significantly lower in group C than in group B. When G. biloba and dexamethasone groups were compared with each other, thicknesses of basement membrane and subepithelial smooth muscle were found to be lower in group D than in groups B and C. G. biloba alleviates all established chronic histological changes of lung except smooth muscle thickness in a mouse model of asthma.

EFFICACY OF SULPHASALAZINE ON LUNG HISTOPATHOLOGY IN A MURINE MODEL OF CHRONIC ASTHMA

Sulphasalazine is a specific inhibitor of nuclear factor kappa B (NF-κ B) which plays a key role in asthma. To determine the impact of sulphasalazine in the treatment of chronic asthma, BALB/c mice were sensitized and challenged with ovalbumin. Mice with experimentally induced asthma in group I received saline, group II sulphasalazine 200 mg/kg, group III sulphasalazine 300 mg/kg, and group IV dexamethasone 1 mg/kg intraperitoneally once a day in the last 7 days of the challenge period. Histological findings of the airways were evaluated by light and electron microscopies. Dexamethasone and sulphasalazine in both doses significantly improved all airway histopathologic parameters of asthma except numbers of goblet cells. Both doses of sulphasalazine improved thicknesses of basement membrane better than dexamethasone. Dexamethasone reduced the number of mast cells better than sulphasalazine (200 mg/kg). Further studies are needed to evaluate the efficacy of sulphasalazine in the treatment of asthma.

Ginseng ameliorates chronic histopathologic changes in a murine model of asthma.

Currently, asthma therapies are effective in reducing inflammation but airway remodeling is poorly responsive to these agents. New therapeutic options that have fewer side effects and reverse chronic changes in the lungs are essential. This study aimed to determine the efficacy of oral administration of ginseng on lung histopathology in a murine model of chronic asthma. BALB/c mice were divided into four groups: control, placebo, ginseng, and dexamethasone. All mice except those in the control group were sensitized and challenged with ovalbumin. Then, mice in the ginseng group were given 2 gr/kg per day of ginseng and mice in the dexamethasone group received 1 mg/kg per day of dexamethasone via orogastic gavage once daily for 1 week. Lung histopathology was evaluated by using light and electron microscopy in all groups. All of the chronic changes of airways in the ginseng group were significantly ameliorated when compared with the placebo group. When compared with the dexamethasone group, the ginseng group had significantly lower numbers of mast cell count. Thicknesses of basement membrane, epithelium, and subepithelial smooth muscle were not statistically different between the ginseng and dexamethasone groups. Goblet cell numbers were much more reduced in the dexamethasone group. Ginseng is effective in resolving the established chronic histopathological changes of the lungs in the murine model of asthma.

A New Method for Detecting Pedicular Wall Perforation During Pedicle Screw Insertion

Study Design. Sensitivity, specificity, and predictive value analyses of a method that can be used to detect pedicular wall perforation during pedicle screw insertion were assessed. Objective. To determine the accuracy of observing the fatty material expelled during pedicle screw insertion for detecting pedicular wall perforations. Summary of Background Data. Although many methods for safe and accurate insertion of a pedicle screw are described, the rates of misplacement still are high, and complications may occur from improper placement of pedicle screws. Computer-assisted insertion techniques are reported to be very accurate, but these techniques are not yet commonly available. Methods. In this study, 74 pedicle screw insertions were observed for the material expelled after drilling for the pedicle screw. The outflows of blood and fatty particles were recorded separately. The position of the pedicle screws after surgery was verified by computed tomography. The specificity, sensitivity, positive and negative predictive values, and kappa statistics were assessed. Results. Visible fatty particles were observed during 51 pedicle screw insertions. The histologic analysis showed that the fatty particles were coming from the bone marrow of the corpus. For the observation of fatty particles in detecting perforations along the pedicle screw pathway, the specificity was 98%, the sensitivity 73%, the positive predictive value 84%, the negative predictive value 95%, and the kappa statistic 0.74. Conclusions. The observation of fatty particles in the blood that comes out after drilling for the pedicle screw may indicate that there is no perforation along the pedicle screw pathway. The observation is easy to perform and does not require any special instruments. Therefore, it can be used alone or in combination with other methods to improve the accuracy of pedicle screw insertion.