Voclosporin promotes neurological function recovery by inhibiting inflammation and maintaining blood-brain barrier integrity following rtPA reperfusion after MCAO in mice.

IF 4.6 2区医学 Q2 IMMUNOLOGY

Inflammopharmacology Pub Date : 2025-04-24 DOI:10.1007/s10787-025-01757-3

Yangmin Zheng, Shubei Ma, Wei Sun, Feng Yan, Yumin Luo

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引用次数: 0

Abstract

Hemorrhagic transformation (HT) is the most serious complication after rtPA thrombolytic therapy in patients with acute ischemic stroke, which greatly limits the clinical application of rtPA. rtPA disruption of the blood-brain barrier (BBB) by inducing inflammation after cerebral ischemia may be an important mechanism for the development of HT, and maintaining BBB integrity can significantly reduce the risk of HT. Our study found that a new generation of calcineurin inhibitors, voclosporin can improve neurological function, reduce neuronal damage, and reduce cerebral infarction volume in mice. By Evans blue extravasation assay and cerebral water content measurement, it was found that voclosporin could improve BBB injury and reduce brain edema caused by rt-PA. The ELISA and immunofluorescence experiments further proved that voclosporin can reduce the expression of IL-1β/TNF-α, increase the expression of IL-10/IL-4, and protect the integrity of the BBB by promoting microglia/macrophage to M2 type polarization, providing new thinking for clinical rtPA combined therapy to alleviate BBB damage.

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volosporin通过抑制炎症和维持小鼠MCAO后rtPA再灌注后血脑屏障的完整性来促进神经功能恢复。

出血转化（HT）是急性缺血性脑卒中患者rtPA溶栓治疗后最严重的并发症，极大地限制了rtPA的临床应用。rtPA在脑缺血后通过诱导炎症破坏血脑屏障（BBB）可能是HT发生的重要机制，维持血脑屏障的完整性可显著降低HT发生的风险。我们的研究发现，新一代钙调磷酸酶抑制剂voclosporin可以改善小鼠神经功能，减少神经元损伤，减少脑梗死体积。通过Evans蓝色外渗试验和脑含水量测定，发现氯菌素可改善血脑屏障损伤，减轻rt-PA所致脑水肿。ELISA和免疫荧光实验进一步证明，菌素可通过促进小胶质细胞/巨噬细胞向M2型极化，降低IL-1β/TNF-α的表达，增加IL-10/IL-4的表达，保护血脑屏障的完整性，为临床rtPA联合治疗减轻血脑屏障损伤提供新思路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY

CiteScore

8.00

自引率

3.40%

发文量

200

期刊介绍： Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas: -Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states -Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs -Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents -Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain -Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs -Muscle-immune interactions during inflammation [...]