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T lymphocytes play a vital role in the immune‐inflammatory response following a stroke. However, the specific mechanisms behind the contrasting functions of T cells in the brain and peripheral tissues after a stroke remain unclear and require further investigation. T‐cell receptors (TCRs) are essential in controlling how T lymphocytes develop and become active. This study aims to gain a deeper understanding of the biological function of T lymphocytes by analyzing the TCR repertoire in patients who have experienced an acute ischemic stroke (AIS). High‐throughput TCR sequencing was conducted on peripheral blood samples from 25 AIS patients and 10 healthy controls. We compared the percentage of T cells and the characteristics of the TCR repertoire, specifically focusing on the recombination of V(D)J gene fragments and the diversity of the complementarity determining region 3 (CDR3) of the Vβ gene. Additionally, this study analyzed the potential biological significance of the skewed TCR repertoire in AIS patients. In patients with AIS, the proportion of circulating lymphocytes (LY%) decreased while the systemic immune‐inflammatory index (SII) increased compared to healthy controls. The average number of TCR read pairs decreased, corresponding with the presence of lymphopenia. However, the recombination of V(D)J gene fragments, the number of CDR3 clonotypes, and the diversity of CDR3 was elevated in the peripheral blood of AIS patients. Furthermore, the increased number of CDR3 amino acid or nucleotide clonotypes was negatively correlated with neurologic deficits but positively correlated with AIS patients' systemic immune condition and functional outcomes. Our findings suggest that both immunosuppression and enhanced antigen‐specific T‐cell response may exist in the periphery of the AIS patients. Further investigation into the mechanisms underlying these opposing changes may lead to the discovery of novel targets to reverse immunosuppression or mitigate the detrimental effects of T cells in the lesioned brain of AIS patients. [ABSTRACT FROM AUTHOR]

Metal ions play a pivotal role in maintaining optimal brain function within the human body. Nevertheless, the accumulation of these ions can result in irregularities that lead to brain damage and dysfunction. Disruptions of metal ion homeostasis can result in various pathologies, including inflammation, redox dysregulation, and blood-brain barrier disruption. While research on metal ions has chiefly focused on neurodegenerative diseases, little attention has been given to their involvement in the onset and progression of stroke. Recent studies have identified cuproptosis and confirmed ferroptosis as significant factors in stroke pathology, underscoring the importance of metal ions in stroke pathology, including abnormal ion transport, neurotoxicity, blood-brain barrier damage, and cell death. Additionally, it provides an overview of contemporary metal ion chelators and detection techniques, which may offer novel approaches to stroke treatment. • The transport of metal ions in the normal brain and changes during a stroke. • The relationship between metal ion imbalance and the blood-brain barrier disruption after stroke. • The various pathways of cell death related to metal ions, with a focus on the role of these ions in these processes. • Different methods of detecting metal ions. • Current strategies for metal ion chelation therapy. [ABSTRACT FROM AUTHOR]

Rationale : The vagus nerve, which connects the brain and gastrointestinal tract, helps to maintain immune balance in the intestines. Gut-specific integrins, on the other hand, help to keep immune cells in the intestines. Since immune cells from outside the intestines can significantly affect the outcome of strokes, we investigated how immune cells from the intestines affect the immune response in the brain during intracerebral hemorrhage (ICH). Methods : We aimed to examine the impact of vagal innervation on intestinal immunocyte trafficking and its influence on ICH outcomes using Kikume Green-Red (KikGR) and wildtype (WT) mice, with or without prior subdiaphragmatic vagotomy (SDV). Furthermore, we sought to elucidate the regulatory effects of vagal innervation on intestinal immunocyte trafficking by activating α7 nicotinic acetylcholine receptors (α7nAChR) in WT mice that underwent ICH after SDV. Additionally, we explored the potential intermediary role of gut-selective integrins in cholinergic transmitters-mediated intestinal immunocyte trafficking. Our methodology encompassed in vivo fluorescence imaging, flow cytometry, Western blotting, immunofluorescence staining, histopathology, and behavioral assessments to evaluate the outcomes. Results : Our findings reveal that during the acute phase of ICH, intestinal immunocytes migrated to various anatomical locations, including the circulation, hemorrhagic brain, meninges, and deep cervical lymph nodes. Pertinently, SDV resulted in diminished expression of α4β7 and αEβ7 integrins on immunocytes, leading to heightened intestinal immunocyte trafficking and exacerbated ICH outcomes. Conversely, the administration of α7nAChR agonists countered the adverse effects of vagotomy on α4β7 and αEβ7 integrin expression, thereby constraining the migration of immune cells from the intestines after ICH. The implication of α4β7 and αEβ7 integrins in this setting was supported by the ineffective influence of α7nAChR agonists on the trafficking of intestinal immunocytes enhanced by administering beta-7 integrin antagonists, such as etrolizumab. It was further supported by the exacerbated ICH outcomes by administering beta-7 integrin antagonists like etrolizumab alone. Conclusion : The identification of vagus nerve-mediated modulation of α4β7 and αEβ7 integrin expression in the trafficking of immune cells within the intestinal tract holds significant implications. This discovery presents new opportunities for developing therapeutic interventions for ICH and stimulates further investigation in this area., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Central poststroke pain (CPSP) is a medical complication that arises poststroke and significantly impacts the quality of life and social functioning of affected individuals. Despite ongoing research, the exact pathomechanisms of CPSP remain unclear, and practical treatments are still unavailable. Our review aims to systematically analyse current clinical and preclinical studies on CPSP, which is critical for identifying gaps in knowledge and guiding the development of effective therapies. The review will clarify the clinical characteristics, evaluation scales and contemporary therapeutic approaches for CPSP based on clinical investigations. It will particularly emphasise the CPSP model initiated by stroke, shedding light on its underlying mechanisms and evaluating treatments validated in preclinical studies. Furthermore, the review will not only highlight methodological limitations in animal trials but also offer specific recommendations to researchers to improve the quality of future investigations and guide the development of effective therapies. This review is expected to provide valuable insights into the current knowledge regarding CPSP and can serve as a guide for future research and clinical practice. The review will contribute to the scientific understanding of CPSP and help develop effective clinical interventions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)