The effect of the HMGB1/RAGE/TLR4/NF-κB signalling pathway in patients with idiopathic epilepsy and its relationship with toxoplasmosis.

This study aims to investigate the relationship between toxoplasmosis and this pathway, which may be effective in the formation of epilepsy by acting through the HMGB1/RAGE/TLR4/NF-κB signalling pathway in patients with idiopathic epilepsy. In the study, four different experimental groups were formed by selecting Toxoplasma gondii IgG positive and negative patients with idiopathic epilepsy and healthy controls. Experimental groups were as follows: Group 1: Epilepsy+/Toxo- (E+, T-) (n = 10), Group 2: Epilepsy-/Toxo- (E-, T-) (n = 10), Group 3: Epilepsy-/Toxo+ (E-, T+) (n = 10), Group 4: Epilepsy+/Toxo+ (E+, T+) (n = 10). HMGB1, RAGE, TLR4, TLR1, TLR2, TLR3, IRAK1, IRAK2, IKBKB, IKBKG, BCL3, IL1ß, IL10, 1 L8 and TNFα mRNA expression levels in the HMGB/RAGE/TLR4/NF-κB signalling pathway were determined by quantitative simultaneous PCR (qRT-PCR) after collecting blood samples from all patients in the groups. Statistical analysis was performed by one-way ANOVA followed by LSD post-hoc tests, and p < 0.05 was considered to denote statistical significance. The gene expression levels of HMGB1, TLR4, IL10, IL1B, IL8, and TLR2 were significantly higher in the G1 group than in the other groups (p < 0.05). In the G3 group, RAGE and BCL3 gene expression levels were significantly higher than in the other groups (p < 0.05). In the G4 group, however, IRAK2, IKBKB, and IKBKG gene expression levels were significantly higher than in the other groups (p < 0.05). HMGB1, TLR4, IRAK2, IKBKB, IL10, IL1B, IL1B, and IL8 in this signalling pathway are highly expressed in epilepsy patients in G1 and seizures occur with the stimulation of excitatory mechanisms by acting through this pathway. The signalling pathway in epilepsy may be activated by HMGB1, TLR4, and TLR2, which are considered to increase the level of proinflammatory cytokines. In T. gondii, this pathway is activated by RAGE and BCL3.

Neuroprotective effects of goji berry (Lycium barbarum L.) polysaccharides on depression-like behavior in ovariectomized rats: behavioral and biochemical evidence.

AIM: To assess the protective effects of goji berry (Lycium barbarum L.) polysaccharides (LBP) on depression-like behavior in ovariectomized rats and to elucidate the mechanisms underlying these effects. METHODS: One hundred female Wistar albino rats (three months old) were randomly assigned either to ovariectomy (n=50) or sham surgery (n=50). After a 14-day recovery period, the groups were divided into five treatment subgroups (10 per group): high-dose LBP (200 mg/kg), low-dose LBP (20 mg/kg), imipramine (IMP, 2.5 mg/kg), 17-beta estradiol (E2, 1 mg/kg), and distilled water. Then, rats underwent a forced swimming test. We also determined the levels of serum antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde), E2 levels, hippocampal brain-derived neurotrophic factor (BDNF), 5HT2A receptor, and transferase dUTP nick end labeling (TUNEL)-positive cells. RESULTS: Both low-dose LBP and imipramine decreased depression-like behavior by increasing serum superoxide dismutase activity and by decreasing serum malondialdehyde level. Furthermore, low-dose LPB, high-dose LBP, and imipramine increased the number of 5-HT2A receptor- and BDNF-positive cells but decreased the number of TUNEL-positive cells in the hippocampus. CONCLUSION: This is the first study to show the antidepressant effect of LBP. Although additional research is needed, LBP may be considered a potential new antidepressant.

Can hyperoxic stress cause susceptibility to acute seizure in the neonatal period?: a rat study.

Objective: Preterm neonates encounter hyperoxia relatively early, and are more exposed to hyperoxic stress due to their insufficient antioxidant defense mechanisms. This study was planned around the hypothesis that this hyperoxic effect may cause a disposition to future acute seizures. Methods: This study was composed of two main groups Hyperoxy and Control (Room air with normal O2 levels) Groups. Group 1 - hyperoxia (Study): The experimental group consisted of premature newborn rats exposed to hyperoxia with their dams from birth to postnatal day 5. Group 2 - room air (Control): The group was not exposed to hyperoxia and housed the same room air and temperature as their dams. Female, Acute Epilepsy Female, Male, Acute Epilepsy Male, and a total of eight subgroups were formed in both the control and hyperoxia groups. When the rats were two months old, intracranial electrodes were attached to obtain electrocorticography (ECoG) recordings. Pre-model recordings were taken, after which an acute pentylenetetrazole (PTZ) model of absence seizure was induced by the intraperitoneal administration of PTZ at 50 mg/kg. ECoG records were examined using the PowerLab system for 180 min. Spike wave number and duration, Spike wave frequency and amplitude data were evaluated.Results: Seven female and three male rats were exposed to hyperoxia, and a control group of five female and three male rats were included in the study. The median interquartile range for spike wave latency in the hyperoxia and control groups were 1112 (644-1545) and 654 (408-1152), frequency 4476 (3120-7421) and 3934 (2264-4704), and amplitude data 0.68 (0.59-0.79) and 0.52 (0.37-0.67), respectively. Although a difference was observed in median values capable of constituting susceptibility to epilepsy, the difference was not statistically significant (p > 0.05). In terms of gender, spike-wave counts were significantly higher in female rats (p < 0.05). Females exposed to hyperoxia were more susceptible to epilepsy than both males and females in the control group (p < 0.05).Conclusion: Exposure to hyperoxia in the first days of life of premature neonates due to their susceptibility to oxidative stress and insufficient antioxidant mechanisms, can cause a disposition to acute seizures. As a result, females exposed to hyperoxia during the neonatal period may be prone to epilepsy in maturity.

A comparison of IL-17 and IL-34 concentrations in the cerebrospinal fluid of patients with acute inflammatory demyelinating neuropathy and chronic inflammatory demyelinating polyneuropathy.

OBJECTIVE: The role of interleukins, such as IL-17 and IL-34, in the pathogenesis of autoimmune diseases has been established in the literature. In the current study, we aimed to identify the concentrations of IL-17 (IL-17A, IL-17F) and IL-34 in the cerebrospinal fluid (CSF) of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and acute inflammatory demyelinating neuropathy (AIDN). METHODS: We included in this study 8 patients with CIDP (none of them receiving immunomodulatory or immunosuppressant therapy), 7 patients with Guillain-Barre syndrome (GBS, AIDN), and 7 control subjects. The CIDP and AIDN diagnoses were made by clinical evaluation and electrophysiological investigations according to international criteria. CSF samples were obtained appropriately, and the levels of IL-17A, IL-17F, and IL-34 were measured by ELISA kits. RESULTS: The concentrations of IL-17A, IL-17F, and IL-34 were higher in those with CIDP and AIDN compared to the controls (p=0.005, p=0.01, and p=0.001, respectively). While IL-34 levels were significantly higher in AIDN patients than in CIDP patients (p=0.04), there were no significant differences between the AIDN and CIDP groups with regard to the levels of IL-17A and IL-17F (p=0.4 and p=0.2, respectively). CONCLUSION: Our results indicate that IL-17A, IL-17F, and IL-34 levels may have a role in CIDP and AIDN. Furthermore, the difference in the IL-34 levels of patients with AIDN and CIDP may indicate an important difference between the pathogenesis of these two sets of the disease.

Anxiolytic, antioxidant, and neuroprotective effects of goji berry polysaccharides in ovariectomized rats: experimental evidence from behavioral, biochemical, and immunohistochemical analyses.

Recent studies have indicated that polysaccharides, the main component of the Lycium barbarum L. fruit, have beneficial effects (e.g., anxiolytic, antioxidant, and neuroprotective) on humans and rodents. However, the effects of different dosages of such polysaccharides on ovariectomized rats and their underlying mechanisms in the brain have not been evaluated in the literature. Here, we aimed to evaluate the effects of the high and low doses of polysaccharides obtained from Lycium barbarum fruits (HD-LBP and LD-LBP, respectively) on anxious behaviors via behavioral (using the OFT and EPM), biochemical (using ELISA), and immunohistochemical (using immunohistochemical staining) measures in detail. Two weeks after ovariectomy, the rats were randomly assigned to either the treatment conditions [control (DW, 3 mL/kg, p.o., per day), LD-LBP (20 mg/kg, 3 mL/kg, p.o., per day), HD-LBP (200 mg/kg, 3 mL/kg, p.o., per day), 17 ß-ES (1 mg/kg, 3 mL/kg, p.o., per day), DZ(1 mg/kg, 3 mL/kg, p.o., per day)] or operation type [SHAM (pseudo-ovariectomized) and OVX (ovariectomized)]. The treatments were applied for 30 consecutive days, and then serum and brain tissue samples of all rats were collected. Biochemical (SOD, CAT, GPX, MDA, and 17 ß-ES) and immunohistochemical (BDNF, SER, and apoptosis) analyses of the samples were performed as well. The rats administered HD-LBP and LD-LBP were less anxious than the control groups. The HD-LBP-treated rats had high levels of SOD and low levels of MDA in their serum samples. Moreover, HD-LBP and drug-treated groups had a high number of SER receptors and BDNF-positive cells and a low number of TUNEL-positive cells in their hippocampal brain tissues. The HD-LBP treatments decrease anxious behavior by increasing antioxidant enzyme activities, hippocampal SER and BDNF neurotransmitter levels and decreasing the TUNEL-positive cell count of ovariectomized rats. Given these findings, we suggest that menopause-induced symptoms of anxiety can be reduced by polysaccharides obtained from goji berry fruits, and that these findings will be beneficial for the production studies of natural herbal-origin antianxiety (anxiolytic) drugs in the future.

A comparison of IL-17 and IL-34 concentrations in the cerebrospinal fluid of patients with acute inflammatory demyelinating neuropathy and chronic inflammatory demyelinating polyneuropathy

SUMMARY OBJECTIVE: The role of interleukins, such as IL-17 and IL-34, in the pathogenesis of autoimmune diseases has been established in the literature. In the current study, we aimed to identify the concentrations of IL-17 (IL-17A, IL-17F) and IL-34 in the cerebrospinal fluid (CSF) of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and acute inflammatory demyelinating neuropathy (AIDN). METHODS: We included in this study 8 patients with CIDP (none of them receiving immunomodulatory or immunosuppressant therapy), 7 patients with Guillain-Barre syndrome (GBS, AIDN), and 7 control subjects. The CIDP and AIDN diagnoses were made by clinical evaluation and electrophysiological investigations according to international criteria. CSF samples were obtained appropriately, and the levels of IL-17A, IL-17F, and IL-34 were measured by ELISA kits. RESULTS: The concentrations of IL-17A, IL-17F, and IL-34 were higher in those with CIDP and AIDN compared to the controls (p=0.005, p=0.01, and p=0.001, respectively). While IL-34 levels were significantly higher in AIDN patients than in CIDP patients (p=0.04), there were no significant differences between the AIDN and CIDP groups with regard to the levels of IL-17A and IL-17F (p=0.4 and p=0.2, respectively) CONCLUSION: Our results indicate that IL-17A, IL-17F, and IL-34 levels may have a role in CIDP and AIDN. Furthermore, the difference in the IL-34 levels of patients with AIDN and CIDP may indicate an important difference between the pathogenesis of these two sets of the disease.

RESUMO OBJETIVO: O papel das interleucinas, como IL-17 e IL-34, na patogênese da doença auto-imune foi estabelecido na literatura. No presente estudo, objetivamos identificar as concentrações de IL-17 (IL-17A, IL-17F) e IL-34 no líquido cefalorraquidiano (LCR) de pacientes com polineuropatia desmielinizante inflamatória crônica (CIDP) e neuropatia desmielinizante inflamatória aguda (AIDN). MÉTODOS: incluímos neste estudo 8 pacientes com CIDP (nenhum deles recebendo terapia imunomoduladora ou imunossupressora), 7 pacientes com síndrome de Guillain-Barre (GBS, AIDN) e 7 indivíduos controle. Os diagnósticos CIDP e AIDN foram feitos por avaliação clínica e investigações eletrofisiológicas de acordo com critérios internacionais. As amostras de LCR foram obtidas adequadamente e os níveis de IL-17A, IL-17F e IL-34 foram medidos através de kits ELISA. RESULTADOS: As concentrações de IL-17A, IL-17F e IL-34 foram maiores naqueles com CIDP e AIDN em comparação aos controles (p = 0,005, p = 0,01 ep = 0,001, respectivamente). Enquanto os níveis de IL-34 foram significativamente mais altos nos pacientes com AIDN do que nos pacientes com CIDP (p = 0,04), não houve diferenças significativas entre os grupos com AIDN e CIDP em relação aos níveis de IL-17A e IL-17F (p = 0,4 ep = 0,2, respectivamente) CONCLUSÃO: Nossos resultados indicam que os níveis de IL-17A, IL-17F e IL-34 podem ter um papel no CIDP e no AIDN. Além disso, a diferença nos níveis de IL-34 de pacientes com AIDN e CIDP pode indicar uma diferença importante entre a patogênese desses dois conjuntos de doenças.