Neuroprotection on ischemic brain injury by Mg2+/H2 released from endovascular Mg implant

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials Pub Date : 2024-08-30 DOI:10.1016/j.bioactmat.2024.08.019

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Abstract

Most acute ischemic stroke patients with large vessel occlusion require stent implantation for complete recanalization. Yet, due to ischemia-reperfusion injury, over half of these patients still experience poor prognoses. Thus, neuroprotective treatment is imperative to alleviate the ischemic brain injury, and a proof-of-concept study was conducted on “biodegradable neuroprotective stent”. This concept is premised on the hypothesis that locally released Mg²⁺/H₂ from Mg metal within the bloodstream could offer synergistic neuroprotection against reperfusion injury in distant cerebral ischemic tissues. Initially, the study evaluated pure Mg's neuroactive potential using oxygen-glucose deprivation/reoxygenation (OGD/R) injured neuron cells. Subsequently, a pure Mg wire was implanted into the common carotid artery of the transient middle cerebral artery occlusion (MCAO) rat model to simulate human brain ischemia/reperfusion injury. In vitro analyses revealed that pure Mg extract aided mouse hippocampal neuronal cell (HT-22) in defending against OGD/R injury. Additionally, the protective effects of the Mg wire on behavioral abnormalities, neural injury, blood-brain barrier disruption, and cerebral blood flow reduction in MCAO rats were verified. Conclusively, Mg-based biodegradable neuroprotective implants could serve as an effective local Mg²⁺/H₂ delivery system for treating distant cerebral ischemic diseases.

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血管内镁植入物释放的 Mg2+/H2 对缺血性脑损伤的神经保护作用

大多数大血管闭塞的急性缺血性脑卒中患者需要植入支架才能完全再通畅。然而，由于缺血再灌注损伤，半数以上患者的预后仍然不佳。因此，为减轻缺血性脑损伤，神经保护治疗势在必行，一项关于 "可降解神经保护支架 "的概念验证研究就此展开。这一概念的前提假设是，从血液中的金属镁局部释放出的 Mg2+/H2 可以对远处脑缺血组织的再灌注损伤提供协同神经保护。研究首先利用氧-葡萄糖剥夺/再氧合（OGD/R）损伤的神经元细胞评估了纯镁的神经活性潜力。随后，将纯镁丝植入瞬时大脑中动脉闭塞（MCAO）大鼠模型的颈总动脉，模拟人类脑缺血再灌注损伤。体外分析表明，纯镁提取物有助于小鼠海马神经元细胞（HT-22）抵御OGD/R损伤。此外，还验证了镁线对 MCAO 大鼠行为异常、神经损伤、血脑屏障破坏和脑血流量减少的保护作用。最终，镁基生物可降解神经保护性植入物可作为一种有效的局部 Mg2+/H2 递送系统，用于治疗远处脑缺血疾病。

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来源期刊

Bioactive Materials Biochemistry, Genetics and Molecular Biology-Biotechnology

CiteScore

28.00

自引率

6.30%

发文量

436

审稿时长

20 days

期刊介绍： Bioactive Materials is a peer-reviewed research publication that focuses on advancements in bioactive materials. The journal accepts research papers, reviews, and rapid communications in the field of next-generation biomaterials that interact with cells, tissues, and organs in various living organisms. The primary goal of Bioactive Materials is to promote the science and engineering of biomaterials that exhibit adaptiveness to the biological environment. These materials are specifically designed to stimulate or direct appropriate cell and tissue responses or regulate interactions with microorganisms. The journal covers a wide range of bioactive materials, including those that are engineered or designed in terms of their physical form (e.g. particulate, fiber), topology (e.g. porosity, surface roughness), or dimensions (ranging from macro to nano-scales). Contributions are sought from the following categories of bioactive materials: Bioactive metals and alloys Bioactive inorganics: ceramics, glasses, and carbon-based materials Bioactive polymers and gels Bioactive materials derived from natural sources Bioactive composites These materials find applications in human and veterinary medicine, such as implants, tissue engineering scaffolds, cell/drug/gene carriers, as well as imaging and sensing devices.