The effect of Lipopolysaccharide (LPS) pretreatment on hippocampal apoptosis in traumatic rats.

Objectives: Traumatic brain injury (TBI) is a serious medical problem that affects the quality of life. Apoptosis is a form of programmed cell death that happens after trauma. Effector caspases are responsible for initiating apoptosis.Methods: In the present study, we examined the effect of LPS preconditioning (0.1 and 0.5 mg/kg, ip; 5 days prior controlled cortical injury) on apoptosis, 4 and 12 hours after trauma. We investigated possible mechanisms on the expression of caspase3 and caspase7 in hippocampal CA1 and CA3 areas by using immunohistochemistry and Western blotting techniques and also TUNEL-positive cells.Results: Higher expression of caspase3 and caspase7 were accompanied by a higher number of dead neurons in traumatic rats 4 and 12 hours after trauma(P < 0.05). LPS preconditioning decreased caspase3 and caspase7over-expression and the number of dead neurons in the hippocampus(P < 0.05).Discussion: Our data indicate that LPS preconditioning inhibits neural damage and apoptosis induced by trauma in the hippocampus.

Serum pro-inflammatory and anti-inflammatory cytokines and the pathogenesis of experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) as an experimental model of multiple sclerosis (MS) is characterized by demyelination, infiltration of inflammatory cells into the nervous system and dysregulation of serum inflammatory cytokines. We investigated the correlation of serum cytokines and other inflammatory markers with the EAE pathogenesis. After EAE induction, the levels of different serum cytokine/inflammatory mediators were measured. Furthermore, motor functions, myelination, and lymphocyte infiltration in EAE mice were also assessed. Our results revealed that the serum concentrations of T-helper 1 (Th1) and Th17 cytokines, interleukin (IL)-6, IL-1ß, IL-1α and prostaglandin E2 in EAE mice were significantly higher than controls. The ratios of pro- to anti-inflammatory cytokines were different between the EAE and the control group. A statistically significant positive correlation was found between the IL-6/IL-10 ratio and the EAE severity, demyelination rate, and lymphocyte infiltration in EAE mice. Results indicate that the profiles of serum pro- and anti-inflammatory cytokines might be useful as biomarkers for monitoring the pathological manifestation of EAE. Furthermore, evaluating the dynamic interplay of serum cytokine levels and the correlation with pathogenic mechanisms of EAE may provide diagnostic and therapeutic insights for MS and some other inflammatory disorders.

Curcumin attenuates harmful effects of arsenic on neural stem/progenitor cells.

OBJECTIVE: Arsenic, an environmental pollutant, decreases neuronal migration as well as cellular maturation and inhibits the proliferation of neural progenitor cells. Curcumin has been described as an antioxidant and neuroprotective agent with strong therapeutic potential in some neurological disorders. Human adipose-derived stem cells (hADSCs), a source of multipotent stem cells, can self-renew and differentiate into neural cells. The aim of the present study was to investigate the preventive effect of curcumin against arsenic toxic effects on the viability, telomerase activity, and apoptosis of neural stem/progenitor cells (NSPCs) derived from hADSCs. MATERIALS AND METHODS: The characteristics of human adipose tissue were identified by immunocytochemistry for surface markers namely, CD105, CD73, and CD90. Using neurosphere assay, hADSCs were differentiated into neuronal cells. To characterize neural cells, expression of nestin, SOX2, MAP2, and GFAP were assessed by immunocytochemistry. Cytotoxicity and viability of NSPCs were evaluated by MTT assay. Reactive oxygen species (ROS) generated by arsenic exposure, were measured and caspase 3/7 activity and caspase-3 processing as well as the telomerase activity were determined. RESULTS: The isolated hADSCs positively expressed CD105, CD73, and CD90. Nestin, Sox2, GFAP, and MAP2 were expressed in the neurospheres derived from hADSCs. Curcumin/arsenic co-treatment significantly increased telomerase activity of NSPCs compared to arsenic group. Furthermore, curcumin significantly reduced arsenic-induced apoptosis (via inactivation of caspases) as well as arsenic-associated ROS generation. CONCLUSION: Our findings revealed that curcumin has the potential to prevent harmful effects of arsenic on neurogenesis.

Additive effect of harmane and muscimol for memory consolidation impairment in inhibitory avoidance task.

In the current study, we examined the effect of bilateral intra-dorsal hippocampal (intra-CA1) microinjections of GABAA receptor agents on amnesia induced by a ß-carboline alkaloid, harmane in mice. We used a single-trial step-down passive avoidance task to assess memory retention and then, open-field test to assess locomotor activity. The results indicated that post-training intra-CA1 injections of bicuculline - a GABAA receptor antagonist - had no significant effect, while muscimol (0.01 and 0.1µg/mouse) - a GABAA receptor agonist - impaired memory consolidation. Post-training intra-peritoneal (i.p.) infusion of harmane (3 and 5mg/kg) decreased memory consolidation. Furthermore, post-training intra-CA1 administration of sub-threshold dose of bicuculline (0.001µg/mouse) restored, whereas muscimol (0.001µg/mouse) potentiated impairment of memory consolidation induced by harmane. The isobologram analysis revealed that there is an additive effect between harmane and muscimol on impairment of memory consolidation. Moreover, all above doses of drugs did not alter locomotor activity. These findings suggest that GABAA receptors of the CA1 area, at least partly, play a role in modulating the effect of harmane on memory consolidation.