Mechanisms of inflammation after ischemic stroke in brain-peripheral crosstalk.

Stroke is a devastating disease with high morbidity, disability, and mortality, among which ischemic stroke is more common. However, there is still a lack of effective methods to improve the prognosis and reduce the incidence of its complications. At present, there is evidence that peripheral organs are involved in the inflammatory response after stroke. Moreover, the interaction between central and peripheral inflammation includes the activation of resident and peripheral immune cells, as well as the activation of inflammation-related signaling pathways, which all play an important role in the pathophysiology of stroke. In this review, we discuss the mechanisms of inflammatory response after ischemic stroke, as well as the interactions through circulatory pathways between peripheral organs (such as the gut, heart, lung and spleen) and the brain to mediate and regulate inflammation after ischemic stroke. We also propose the potential role of meningeal lymphatic vessels (MLVs)-cervical lymph nodes (CLNs) as a brain-peripheral crosstalk lymphatic pathway in ischemic stroke. In addition, we also summarize the mechanisms of anti-inflammatory drugs in the treatment of ischemic stroke.

Association between brain structures and migraine: A bidirectional Mendelian randomization study.

Background: Accumulating evidence of clinical and neuroimaging studies indicated that migraine is related to brain structural alterations. However, it is still not clear whether the associations of brain structural alterations with migraine are likely to be causal, or could be explained by reverse causality confounding. Methods: We carried on a bidirectional Mendelian randomization analysis in order to identify the causal relationship between brain structures and migraine risk. Summary-level data and independent variants used as instruments came from large genome-wide association studies of total surface area and average thickness of cortex (33,992 participants), gray matter volume (8,428 participants), white matter hyperintensities (50,970 participants), hippocampal volume (33,536 participants), and migraine (102,084 cases and 771,257 controls). Results: We identified suggestive associations of the decreased surface area (OR = 0.85; 95% CI, 0.75-0.96; P = 0.007), and decreased hippocampal volume (OR = 0.74; 95% CI, 0.55-1.00; P = 0.047) with higher migraine risk. We did not find any significant association of gray matter volume, cortical thickness, or white matter hyperintensities with migraine. No evidence supporting the significant association was found in the reverse MR analysis. Conclusion: We provided suggestive evidence that surface area and hippocampal volume are causally associated with migraine risk.

The impact of serum magnesium and calcium on the risk of epilepsy: A mendelian randomization study.

AIMS: To investigate the causal role of serum magnesium and calcium in epilepsy or any of its subtypes through Mendelian randomization (MR) approach. METHODS: Single nucleotide polymorphisms (SNPs) associated with serum magnesium and calcium were used as the instrumental variables. MR analyses were performed using the summary-level data for epilepsy extracted from International League Against Epilepsy Consortium (15,212 cases and 29,677 controls) to obtain the causal estimates. The analyses were replicated using FinnGen data (7224 epilepsy cases and 208,845 controls), and a meta-analysis was then conducted. RESULTS: The result of combined analyses showed that higher serum magnesium concentrations was associated with a reduced risk of overall epilepsy (odds ratios [OR] = 0.28, 95% confidence interval [CI], 0.12-0.62, p = 0.002). In ILAE, higher serum magnesium was suggestively associated with reduced risks of focal epilepsy (OR = 0.25, 95% CI 0.10-0.62, p = 0.003). However, the results cannot be repeated in sensitivity analyses. As for serum calcium, the results did not reach statistical significance with overall epilepsy (OR = 0.60, 95% CI, 0.31-1.17, p = 0.134). However, genetically predicted serum calcium concentrations showed an inverse association with risk of generalized epilepsy (OR = 0.35, 95% CI, 0.17-0.74, p = 0.006). CONCLUSION: The current MR analysis did not support a causal relationship between serum magnesium and epilepsy, but showed a causally negative association between genetically determined serum calcium and generalized epilepsy.

Stem cells in central nervous system diseases: Promising therapeutic strategies.

Central nervous system (CNS) diseases are a leading cause of death and disability. Due to CNS neurons have no self-renewal and regenerative ability as they mature, their loss after injury or disease is irreversible and often leads to functional impairments. Unfortunately, therapeutic options for CNS diseases are still limited, and effective treatments for these notorious diseases are warranted to be explored. At present, stem cell therapy has emerged as a potential therapeutic strategy for improving the prognosis of CNS diseases. Accumulating preclinical and clinical evidences have demonstrated that multiple molecular mechanisms, such as cell replacement, immunoregulation and neurotrophic effect, underlie the use of stem cell therapy for CNS diseases. However, several issues have yet to be addressed to support its clinical application. Thus, this review article aims to summarize the role and underlying mechanisms of stem cell therapy in treating CNS diseases. And it is worthy of further evaluation for the potential therapeutic applications of stem cell treatment in CNS disease.