CXCL14 exacerbates seizures by inhibiting GABA metabolism in epileptic mice.

OBJECTIVE: Epilepsy is a common central nervous system disorder with pathological mechanisms including inflammation, ion channel impairment, and neurotransmitter imbalance. Despite the rapid development of current anti-epileptic drugs, epilepsy is not well controlled, so there is still a need for research on the mechanisms and new drug targets for epilepsy. CXCL14 is a member of the CXC family of chemokines, and its receptor is currently unknown. Chemokines are the third major communication mediators in the central nervous system and play a role in many diseases. Therefore, we explore the expression of CXCL14 in epilepsy and its possible mechanisms. MATERIALS AND METHODS: We chose the kainic acid (KA) mouse model as the epilepsy model, and studied the expression of CXCL14 in this model by western blot. Subsequently, after knocking down CXCL14, we explored the effect of CXCL14 on seizures by electrophysiology and FJB (Fluoro-Jade B) staining. Western blot and ELISA were used to explore the possible mechanism of CXCL14 affecting seizures. RESULTS: CXCL14 expression gradually increased after a seizure until it peaked at 72 hours and then gradually decreased again. The knockdown of CXCL14 resulted in prolonged seizure latency, decreased seizure grade, and reduced degenerative necrosis of neurons in mice. Levels of GABA (γ-aminobutyric acid), GAD67 (glutamate decarboxylase 67) and GABAA receptor (γ-aminobutyric acid A receptor) were increased. CONCLUSION: Our results suggest that CXCL14 expression is increased after seizures and may exacerbate seizures by regulating GABA metabolism. Based on this, CXCL14 could be a new target for epilepsy treatment and antiepileptic drug development.

Intestinal Flora Composition Determines Microglia Activation and Improves Epileptic Episode Progress.

In response to environmental stimuli, immune memory mediates the plasticity of myeloid cells. Immune training and immune tolerance are two aspects of plasticity. Microglia that are immunologically trained or immunologically tolerant are endowed with a tendency to differentiate into alternative dominant phenotypes (M1/M2). Male C57BL/6 mice (immune-training group, immune-tolerant group, and control group) were used to establish the kainic acid epilepsy model. The seizure grade, duration, latency, hippocampal potential, and energy density were used to evaluate seizures, and the changes in the polarization of microglia were detected by western blot. 16S rDNA sequencing showed that the abundance of Ruminococcus in the immune-tolerant group was the dominant flora. Our research connections Intestinal microorganisms, brain immune status, and epilepsy behavior together. Pro-inflammatory M1 phenotype and anti-inflammatory M2 phenotype mediate and enhance and suppress subsequent inflammation, respectively. We conclude that intestinal microorganisms influence the occurrence and development of epilepsy by regulating the polarization of microglia.

Association between Insulin Resistance and Cognitive Impairment.

The objective of the review was to assess the relationship between insulin resistance and cognitive impairment. Medline, Embase, Web of Science and Cochrane Library were searched. Two independent authors selected studies and extracted data. Quality of included studies was assessed by NOS (Newcastle-Ottawa quality assessment scale). A random-effects model with its 95% confidence intervals (CIs) was considered for meta-analysis. Eight articles including 1,399 subjects were included in this meta-analysis. The article showed a negative association between insulin resistance and cognition (R = - 0.262; 95% CI-0.309, - 0.215). There is evidence that insulin resistance may be a mechanism of cognitive impairment. Key Words: Insulin resistance, Insulin, Cognition, Cognitive impairment, Systematic review, Alzheimer's disease.