Various clinical trials and experimental studies have demonstrated that inflammation following brain ischemia is pivotal in the pathogenesis of stroke. In ischemic stroke, complement component 3 (C3) is critical in the complement cascade and immune recognition. Minutes after ischemic insult, the death of neurocytes orchestrates an inflammatory response characterized by the activation of focal glia, infiltration of peripheral immune cells, and release of cytokines and chemokines to further damage the brain parenchyma and vasculature. During ischemic stroke, the sudden cessation of cerebral blood supply in a vascular territory generates an ischemic core, surrounded by a hypoperfused but potentially salvageable region called the ischemic penumbra. Ischemic stroke accounts for 80-90% of all strokes and results in devastating brain damage and severe neurological deficits. Stroke is the second most frequent cause of death and leading source of permanent disability worldwide. Keywords: blood-brain barrier, selective accumulation, intravenous immunoglobulin, immunomodulatory therapy, ischemic stroke Introduction Furthermore, the early administration of low-dosage MPC-n(IVIg) decreases neurological deficits and mortality by suppressing stroke-induced inflammation in the middle cerebral artery occlusion model.Ĭonclusion: Our findings indicate a promising strategy to efficiently deliver the therapeutics to the ischemic target brain tissue and lower the effective dose of therapeutic drugs for treating ischemic strokes. Moreover, earlier administration of MPC-n(IVIg) more efficiently deliver IVIg to ischemic areas.
Results: MPC-n(IVIg) efficiently crosses the BBB and IVIg selectively accumulates in ischemic areas in a high-affinity choline transporter 1 (ChT1)-overexpression dependent manner via endothelial cells in ischemic areas. In vitro and in vivo experiments verify the effect and safety of MPC-n(IVIg). Methods: We presented a delivery strategy to optimize immunomodulatory therapies by facilitating BBB penetration and selectively delivering intravenous immunoglobulin (IVIg) to ischemic regions using 2-methacryloyloxyethyl phosphorylcholine (MPC)-nanocapsules, MPC-n(IVIg), synthesized using MPC monomers and ethylene glycol dimethyl acrylate (EGDMA) crosslinker via in situ polymerization. However, patients suffering from ischemic stroke do not benefit from immunomodulatory therapies due to the presence of the blood-brain barrier (BBB) and their off-target effects. Immunomodulatory therapies exert multiple remarkable protective effects during ischemic stroke. Ischemic stroke is an acute and severe neurological disease, which leads to disability and death. Select the file that you have just downloaded and select import option Reference Manager (RIS).
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Available fromĬlick on Go to download the file. Early administration of MPC-n(IVIg) selectively accumulates in ischemic areas to protect inflammation-induced brain damage from ischemic stroke. Jin W, Wu Y, Chen N, Wang Q, Wang Y, Li Y, Li S, Han X, Yang E, Tong F, Wu J, Yuan X, Kang C. ✉ Corresponding authors: Jialing Wu (wywjl2009com), Xubo Yuan (xbyuanedu.cn), Chunsheng Kang (kang97061edu.cn)
These authors contributed equally: Weili Jin, Ye Wu Department of Neurology, Tianjin Huanhu Hospital, Tianjin 300350, China.
Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, Tianjin Huanhu Hospital, Tianjin 300350, China. Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, Tianjin 300072, China.ģ. Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Key Laboratory of Post-Neurotrauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, China.Ģ. Weili Jin 1, Ye Wu 1, Ning Chen 2, Qixue Wang 1, Yunfei Wang 1, Yansheng Li 1, Sidi Li 2, Xing Han 2, Eryan Yang 1, Fei Tong 1, Jialing Wu 3, Xubo Yuan 2, Chunsheng Kang 1ġ. Research Paper Early administration of MPC-n(IVIg) selectively accumulates in ischemic areas to protect inflammation-induced brain damage from ischemic stroke
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