Yusufhan Yazir

Resveratrol exerts anti-inflammatory and neuroprotective effects to prevent memory deficits in rats exposed to chronic unpredictable mild stress.

A number of studies have recently focused on the neuroprotective and anti-inflammatory effects of resveratrol. In prior studies, we described its beneficial effects on scopolamine-induced learning deficits in rats. The aim of this study was to investigate the effects of resveratrol on emotional and spatial cognitive functions, neurotropic factor expression, and plasma levels of proinflammatory cytokines in rats exposed to chronic unpredictable mild stress (CUMS), which is known to induce cognitive deficits. Resveratrol (5 or 20mg/kg) was administered intraperitoneally for 35 days. Rats in the CUMS group and in the 5mg/kg resveratrol+CUMS group performed poorly in tasks designed to assess emotional and spatial learning and memory. The 20mg/kg resveratrol+CUMS group showed improved performance compared to the CUMS group. In addition, the CUMS procedure induced lower expression of brain-derived neurotrophic factor and c-Fos in hippocampal CA1 and CA3 and in the amygdala of stressed rats. These effects were reversed by chronic administration of resveratrol (20mg/kg). In addition, plasma levels of tumor necrosis factor-alpha and interleukin-1 beta were increased by CUMS, but were restored to normal by resveratrol. These results indicate that resveratrol significantly attenuates the deficits in emotional learning and spatial memory seen in chronically stressed rats. These effects may be related to resveratrol-mediated changes in neurotrophin factor expression in hippocampus and in levels of proinflammatory cytokines in circulation.

TNF-alpha inhibition prevents cognitive decline and maintains hippocampal BDNF levels in the unpredictable chronic mild stress rat model of depression.

Previous findings have shown that patients with depression express higher levels of proinflammatory cytokines such as TNF-α and IL-6. We have recently found that Infliximab (a TNF-α inhibitor) decreased anhedonia and despair-like behavior in the rat unpredictable chronic mild stress (UCMS) model of depression suggesting that inflammation might play an important role in depression. An increasing number of studies suggest that inflammation is also associated with cognitive impairments. The current study aimed to investigate the effect of UCMS on the cognitive performance of rats and their hippocampal BDNF levels and the effect of chronic Infliximab (5mg/kg/weekly, i.p.) treatment on these measures. Rats were subjected to different types of stressors daily for a period of 56 days to induce depression-like state. The UCMS resulted in impairments in spatial and emotional memory acquisition and retention with no effect on the level of locomotor activity. These behavioral effects of UCMS were accompanied by reduction in the level of BDNF in the CA1 and CA3 regions of the hippocampus. Chronic Infliximab treatment prevented the UCMS-induced cognitive impairments as well as the reduction in the levels of hippocampal brain-derived neurotrophic factor (BDNF). These results suggest that Infliximab improves the spatial and emotional memory impairments induced by chronic stress in rats likely through its effects on hippocampal function by modulating inflammation.

Inhibition of Neuronal Nitric Oxide Synthase and Soluble Guanylate Cyclase Prevents Depression‐Like Behaviour in Rats Exposed to Chronic Unpredictable Mild Stress

Depression is the most common psychiatric disorder. It is well established that endogenous nitric oxide (NO) contributes to chronic unpredictable mild stress (CUMS)‐induced depression. The aim of this study was to investigate brain‐derived neurotropic factor (BDNF) expression in CUMS‐induced depression‐like behaviour in rats. Rats were exposed to CUMS for 5 weeks. A specific and selective nNOS inhibitor, 3‐bromo‐7‐nitroindazole (3‐Br‐7‐NI; 20 mg/kg/day, i.p.), and a specific soluble guanylate cyclase (sGC) inhibitor, 1H‐(1,2,4)oxadiazolo(4,3‐a)quinoxalin‐1‐one (ODQ; 10 mg/kg/day, i.p.), were administered during CUMS. The forced swimming test (FST) was used to assess despair and sucrose consumption, and sucrose preference test was used to assess anhedonia that are the main symptoms of the depression. We show that both 3‐Br‐7‐NI and ODQ administration during CUMS suppressed CUMS‐induced, depression‐like behavioural changes, including reduced sucrose preference, body‐weight and locomotor activity as well as increased immobility time in the FST. CUMS also significantly decreased BDNF protein levels in the CA1 and CA3 regions of the hippocampus, which was reversed by 3‐Br‐7‐NI and ODQ administration. Our findings suggest a novel role for nNOS and sGC‐cGMP in the development of the CUMS model of depression.

LigaSure compared with ligatures and endoclips in experimental appendectomy: how safe is it?

PurposeThe present study aims to compare strength, healing, and inflammation of appendiceal stumps closed by LigaSure Precise™ (Valleylab, Boulder, CO, USA) device, ligatures using polyglactin 910 (Vicryl, Ethicon, Edinburgh, UK) and endoclips (Ligaclip ERCA, Ethicon, OH, USA), and operation time (OT) in experimental appendectomy.MethodsForty-eight Sprague–Dawley rats were divided into two (Group A and B). Each group was further subdivided into three subgroups (AS, AC, AL, BS, BC, BL) containing eight rats. Appendectomy was performed and stump was closed by ligatures in S, by endoclips in C and by LigaSure™ in L subgroups. OT was recorded. In Group A, cecum bursting pressures (BP) were determined instantly after the operation. In Group B, BP, histological evaluations, and measurements of collagen contents estimated by the tissue hydroxyproline (HPL) level were made on the seventh postoperative day. Statistical analyses were performed with Kruskal–Wallis test and Mann–Whitney U test. P value was considered significant at less than 0.05.ResultsBPs of subgroups were comparable on postoperative immediate period and day 7. HPLs and OTs were significantly better in L subgroups. BL had the least inflammation.ConclusionBetter healing, less inflammation, shorter OT, and equal strength achieved with LigaSure™ device comparing with polyglactin 910 ties and endoclips in experimental appendectomy is encouraging.

The effect of etanercept on aortic nitric oxide-dependent vasorelaxation in an unpredictable chronic, mild stress model of depression in rats

Stress has been recognized as a risk factor for cardiovascular disease and depression, but the correlation is not well understood. However, inflammation is known to have a crucial role in both cardiovascular disease and depression. Tumor necrosis factor alpha (TNF-α) is a major cytokine for the activation of neuroendocrine, immune and behavioral responses. Therefore, we aimed to explore the effects of etanercept, an anti-TNF-α fusion protein, on endothelium-dependent vascular reactivity, blood pressure and endothelial nitric oxide synthase (eNOS) immunoreactivity in a model of unpredictable chronic mild stress (UCMS). Male rats were exposed to UCMS for 8 weeks, and etanercept (0.8 mg/kg, weekly) was administered during UCMS induction. The systolic blood pressure was recorded by the tail cuff method, and the relaxant responses of the aorta induced by carbachol, sodium nitroprusside (SNP) and papaverine were evaluated in an isolated organ bath system. UCMS rats exhibited an impaired carbachol-induced relaxant response compared to control rats, but there were no significant differences in the SNP- and papaverine-induced relaxant responses between the control and stressed rats. Etanercept treatment improved the carbachol-induced endothelium dependent relaxations observed in rats that experienced UCMS. No significant change in the systemic blood pressure was observed, but decreased expression of eNOS was detected in the UCMS group. Moreover, there were no significant changes in the etanercept treatment group compared to the control rats. Our results suggest that TNF-α could be a mediator of vascular dysfunction associated with UCMS, which leads to decreased expression of eNOS.

Effects of chronic ethanol treatment on glial fibrillary acidic protein expression in adult rat optic nerve: an immunocytochemical study

Glial fibrillary acidic protein (GFAP) is used as a marker of astrocyte response to various central nervous system injuries. In the present study, the effects of chronic ethanol administration on GFAP immunoreactivity were evaluated in astrocytes of the adult optic nerve head. The results demonstrated that ethanol exposure significantly and dramatically increases GFAP immunoreactivity and the number of immunoreactive astrocytes (p<0.001). In addition, GFAP immunoreactive cells in the optic nerve showed extensive hypertrophy (p<0.001).

Etanercept Improves Cognitive Performance and Increases eNOS and BDNF Expression During Experimental Vascular Dementia in Streptozotocin- induced Diabetes

Diabetes mellitus (DM) is related to an increase in the incidence of vascular dementia. Inflammation is an important cause of endothelial dysfunction and cognitive deficits. The anti -tumor necrosis factor (TNF)-α fusion protein etanercept has been reported to exhibit memory-enhancing effects and endothelial protection. We tested the effect of etanercept on the cognitive endpoints and compared it with the cognitive dysfunction in streptozotocin (STZ )- induced DM rats by using the Morris water maze test (MWMT) and passive avoidance test (PAT). Systolic blood pressure (SBP), thoracic endothelial function, endothelial nitric oxide synthase (eNOS) expression, and hippocampal brain-derived neurotrophic factor (BDNF) expression were assessed. Thirty days after the induction of DM, rats exhibited severe learning and memory deficits associated with endothelial dysfunction and decreased expression of eNOS and BDNF. Chronic treatment with etanercept (0.8 mg/kg, s.c., every week for 30 days) improved cognitive performance, endothelial function, and expression of eNOS and BDNF in DM rats. Furthermore, the memory-improving effects of etanercept were independent of hyperglycemia. These data suggest that etanercept treatment prevents changes in endothelial function, eNOS expression, and hippocampal expression of BDNF and, consequently, vascular dementia in DM rats.

Biochemical effects of experimental epidural hematoma on brain parenchyma of rats

Abstract Introduction: The management of epidural hematoma is classified into surgical or conservative treatment according to clinical and radiologic parameters. In the recent years, the number of paper suggesting conservative management has been increasing. The experimental works that have been performed are based on especially the effects of epidural hematomas. Basic pathophysiologic factors on ischemia result of brain trauma are based on biochemical mediators. Nitric oxide (NO) and malondialdehyde (MDA) are the substances that play important roles in brain damage after trauma. Material and method: In this study, 36 rats are divided into three groups (n=12/group). Epidural hematoma was achieved by 0.1 ml autolog blood in rat epidural space with balloon model. Early and late phase biochemical effects on parenchyma of epidural hematoma operated in a volume which neither alters intracranial pressure (ICP) nor creates shift effect were observed. Biochemical changes of NO and MDA levels were examined in each of three experimental groups. Results: NO values increased significantly in the early group (6 hours) compared with those in the control group. Difference of NO values between the control and late groups was not significant. An increase has been found in MDA values in the control group compared with those in the early group. MDA values of the late group (30 days) were closer to that of the control group. Conclusion: In this study, considering biochemical results, we have found that conservative volumes which neither increase ICP nor cause brain shift do not lead to permanent changes on brain.

Effects of chronic low- and high-dose ethanol intake on the nitrergic relaxations of corpus cavernosum and penile nitric oxide synthase in the rabbit

Epidemiological evidence showed that chronic ethanol consumption is a major risk factor in the development of impotence. The present study investigated the effects of carbachol-, electrical field stimulation (EFS)-, sodium nitroprusside (SNP)- and papaverine-induced relaxant responses in the isolated corpus cavernosum tissues from rabbits submitted to an 12-week course of chronic low (5% v/v) or high ethanol intake (30% v/v). Increased carbachol- and EFS-induced relaxant responses but not SNP and papaverine, were observed in low ethanol-fed rabbits compared with controls. However, impaired carbachol- and EFS-induced relaxant responses were observed in high ethanol-fed rabbits compared with control rabbits. There were no significant differences in SNP- and papaverine-induced relaxant responses between control and high ethanol-fed rabbits. In addition, decreased neuronal nitric oxide synthase (nNOS) and endothelial NOS (eNOS) immunoreactivity in penile tissue were found in high ethanol-fed rabbits, but increased the immunoreactivity in low ethanol-fed group, compared with control group. These results suggest that alterations in nitric oxide (NO) production within the cavernous tissue in the high ethanol-fed rabbits are, at least in part, responsible for the erectile dysfunction.

Comparison of bipolar electrosurgical devices with ligatures and endoclips in the rat appendicitis model

PURPOSE The aim of this study is to compare bipolar radiofrequency-driven vessel sealer, bipolar electrocautery, polyglactin 910 sutures, and endoclips in appendiceal stump closure with respect to operative time, appendiceal stump strength, and inflammation in a rat appendiceal model. METHODS Forty-eight Wistar-Albino rats, which had previously created appendicitis, were divided into 2 (groups A and B). Each group was further subdivided into 4 subgroups (AL, ABPC, AC, AS, BL, BBPC, BC, and BS) each containing 6 rats. An appendectomy was performed, and the stump was closed by bipolar radiofrequency-driven vessel sealer in the L, bipolar electrocautery in the BPC, endoclips in the C, and ligatures in the S subgroups. Cecum bursting pressures were determined instantly after the operation in group A and on the seventh postoperative day in group B. All operative times were measured. Appendices and appendiceal stumps underwent histopathologic examination. Statistical analyses were performed with Kruskal-Wallis and Mann-Whitney U tests. P < .05 was considered significant. RESULTS Bursting pressures of the subgroups were comparable on postoperative immediate period and day 7. Operative times were significantly shorter in the L and BPC subgroups in A and B. Histopathologic examination showed that the inflammation scores were similar in group A. In group B, inflammation parameters were also similar except the necrosis status, which was found to be decreased in BL compared with BC and BS. Necrosis status was significantly lower, and lymphocyte quantity was significantly higher in BL and BBPC compared with AL and ABPC. CONCLUSIONS Bipolar radiofrequency-driven vessel sealer and bipolar electrocautery achieve safe stump closure with satisfactory bursting pressure values in an experimental rat appendicitis model. Decreased operative time and unimpaired healing are encouraging.