Sumatriptan attenuates fear-learning despair induced by social isolation stress in mice: Mediating role of hypothalamic-pituitary-adrenal axis.

OBJECTIVES: Research has demonstrated that chronic stress experienced early in life can lead to impairments in memory and learning. These deficits are attributed to an imbalance in the interaction between glucocorticoids, the end product of the hypothalamic-pituitary-adrenal (HPA) axis, and glucocorticoid receptors in brain regions responsible for mediating memory, such as the hippocampus. This imbalance can result in detrimental conditions like neuroinflammation. The aim of this study was to assess the impact of sumatriptan, a selective agonist for 5-HT 1B/1D receptors, on fear learning capabilities in a chronic social isolation stress model in mice, with a particular focus on the role of the HPA axis. METHODS: Mice were assigned to two opposing conditions, including social condition (SC) and isolated condition (IC) for a duration of five weeks. All mice underwent passive avoidance test, with their subsequent freezing behavior serving as an indicator of fear retrieval. Mice in the IC group were administered either a vehicle, sumatriptan, GR-127935 (a selective antagonist for 5-HT 1B/1D receptors), or a combination of sumatriptan and GR-127935 during the testing sessions. At the end, all mice were sacrificed and samples of their serum and hippocampus were collected for further analysis. RESULTS: Isolation was found to significantly reduce freezing behavior (p<0.001). An increase in the freezing response among IC mice was observed following the administration of varying doses of sumatriptan, as indicated by a one-way ANOVA analysis (p<0.001). However, the mitigating effects of sumatriptan were reversed upon the administration of GR-127935. An ELISA assay conducted before and after the passive avoidance test revealed no significant change in serum corticosterone levels among SC mice. In contrast, a significant increase was observed among IC mice, suggesting hyper-responsiveness of the HPA axis in isolated animals. This hyper-responsiveness was ameliorated following the administration of sumatriptan. Furthermore, both the sumatriptan and SC groups exhibited a similar trend, showing a significant increase in the expression of hippocampal glucocorticoid receptors following the stress of the passive avoidance test. Lastly, the elevated production of inflammatory cytokines (TNF-α, IL-1ß) observed following social isolation was attenuated in the sumatriptan group. CONCLUSION: Sumatriptan improved fear learning probably through modulation of HPA axis and hippocampus neuroinflammation.

Kynurenine pathway and its role in neurologic, psychiatric, and inflammatory bowel diseases.

Tryptophan metabolism along the kynurenine pathway is of central importance for the immune function. It prevents hyperinflammation and induces long-term immune tolerance. Accumulating evidence also demonstrates cytoprotective and immunomodulatory properties of kynurenine pathway in conditions affecting either central or peripheral nervous system as well as other conditions such as inflammatory bowel disease (IBD). Although multilevel association exists between the inflammatory bowel disease (IBD) and various neurologic (e.g., neurodegenerative) disorders, it is believed that the kynurenine pathway plays a pivotal role in the development of both IBD and neurodegenerative disorders. In this setting, there is strong evidence linking the gut-brain axis with intestinal dysfunctions including IBD which is consistent with the fact that the risk of neurodegenerative diseases is higher in IBD patients. This review aims to highlight the role of kynurenine metabolic pathway in various neurologic and psychiatric diseases as well as relationship between IBD and neurodegenerative disorders in the light of the kynurenine metabolic pathway.

Albendazole ameliorates inflammatory response in a rat model of acute mesenteric ischemia reperfusion injury.

BACKGROUND: Acute mesenteric ischemia is known as a life threatening condition. Re-establishment of blood flow in this condition can lead to mesenteric ischemia reperfusion (MIR) injury which is accompanied by inflammatory response. Still, clear blueprint of inflammatory mechanism underlying MIR injury has not been provided. Interestingly, Albendazole has exhibited notable effects on inflammation and cytokine production. In this study, we aimed to evaluate outcomes of MIR injury following pretreatment with Albendazole with respect to assessment of mesenteric inflammation and ischemia threshold. METHODS: Male rats were randomly divided into sham operated, vehicle treated, Albendazole 100 mg/kg and Albendazole 200 mg/kg groups. MIR injury was induced by occlusion of superior mesenteric artery for 30 min followed by 120 min of reperfusion. Samples were utilized for assessment of epithelial survival and villous height. Immunohistochemistry study revealed intestinal expression of TNF-α and HIF-1-α. Gene expression of NF-κB/TLR4/TNF-α/IL-6 was measured using RTPCR. Also protein levels of inflammatory cytokines in serum and intestine were assessed by ELISA method. RESULTS: Histopathological study demonstrated that pretreatment with Albendazole could ameliorate decline in villous height and epithelial survival following MIR injury. Also, systemic inflammation was suppressed after administration of Albendazole. Analysis of possible participating inflammatory pathway could demonstrate that intestinal expression of NF-κB/TLR4/TNF-α/IL-6 is significantly attenuated in treated groups. Eventually, IHC study illustrated concordant decline in mesenteric expression of HIF-1-α/TNF-α. CONCLUSION: Single dose pretreatment with Albendazole could ameliorate inflammatory response and enhance ischemia threshold following induction of MIR injury. More studies would clarify existing causality in this phenomenon.

Medulloblastoma in association with sacral agenesis; a case report.

Medulloblastoma is a congenital brain tumor which can be associated with different congenital anomalies. However, coincidence of cerebellar medulloblastoma with sacral agenesis has not been reported so far. A variety of genetic and/or environmental predisposing factors have been proposed for both diseases. Herein, an unprecedented coincidence of these two conditions is presented. A neonate was born with lumbosacral agenesis, paraplegia, and atrophic legs, and he developed medulloblastoma with three ventricular hydrocephalus 3 years later. Different aspects regarding the embryology and etiology of both ailments are discussed, assuming the possibility that the same genetic and/or environmental risk factors may have played a part in both conditions.

Emergency separation of craniopagus twins: case report.

Craniopagus is a very rare congenital anomaly that tends to affect females more often than males. It is classified as partial or total. Most affected twins are either stillborn or die during the perinatal period. Those who survive birth should undergo detailed radiological evaluations soon after their condition becomes stable so that the precise anatomy of the conjoined part can be defined and surgery can be planned in detail by a multidisciplinary team. Recommendations for decreasing the risk of unsuccessful surgery include performing surgery on an elective basis after extensive preoperative radiological evaluations as well as when the twins are at an acceptable age and weight for a complex surgical separation, generally as staged procedures. In addition, the operation should be performed by a well-equipped expert multidisciplinary team. When one of the conjoined twins dies, however, surgical separation cannot be postponed because the shared circulatory system predisposes the alive child to life-threatening complications, including coagulopathy. The authors report on the successful separation of craniopagus twins performed on an emergency basis at 32 weeks of gestational age because of the sudden death of one of them. At the time of separation surgery, the twins each weighed 1250 g. To the best of the authors' knowledge, this is the youngest age and lowest weight yet reported for successful surgical separation. The surviving twin developed a pseudomeningocele, which required a second operation and placement of a cystoperitoneal shunt 4 months after the operation. Additional surgery is planned to repair a cranial defect that resulted from the pseudomeningocele, but his general physical and mental condition was otherwise good at latest follow-up (12 months after separation surgery).