Feygin Maximillian S, Brenner Alex, Tanweer Omar
Department of Neurosurgery, Baylor College of Medicine, 7200 Cambridge St Ste 9B, Houston, TX 77030, United States.
J Stroke Cerebrovasc Dis. 2025 Feb;34(2):108188. doi: 10.1016/j.jstrokecerebrovasdis.2024.108188. Epub 2024 Dec 10.
The management of acute ischemic stroke (AIS) was revolutionized within the last 15 years with the introduction of mechanical thrombectomy (MT) to standard of care. Despite the success of mechanical thrombectomy (MT) in achieving high recanalization rates for large vessel occlusion, functional independence post-treatment remains suboptimal. The current limitations of MT prompt evaluation of the role of adjunctive pharmacologic neuroprotective therapies to prevent excitotoxicity, cellular apoptosis, and inflammation that cause irreversible neuronal damage during AIS. Magnesium (MgSO) provides an attractive neuroprotectant profile, having many different effects, and is inexpensive, readily available, and has a long-established safety and tolerability profile in the management of myocardial infarction and eclampsia.
This gap between technical success and patient outcomes is largely due to the inability to fully protect brain tissue from infarction during ischemia. MgSO has shown promise in preclinical studies for its neuroprotective properties, including blocking NMDA receptors, increasing cerebral blood flow, and stabilizing ion channels. However, clinical trials, such as FAST-MAG and IMAGES, failed to demonstrate significant benefits when MgSO was administered intravenously, due to delayed drug administration or delivery to target tissue. These trials highlighted the need for faster, more targeted drug delivery. Intra-arterial (IA) administration of MgSO via the catheter used in MT could address these limitations by delivering high doses directly to ischemic brain tissue, potentially enhancing neuroprotection while reducing systemic exposure. Preclinical studies and some clinical trials have demonstrated the safety and feasibility of IA, but not IA MgSO. Further investigation is needed to assess its efficacy.
While past trials have not succeeded, IA administration of neuroprotective agents like MgSO may improve functional outcomes in stroke patients post-MT. Ongoing and future studies will determine if this approach can effectively complement reperfusion strategies, potentially ushering in a new era of stroke care.
在过去15年中，随着机械取栓术（MT）被引入标准治疗方案，急性缺血性卒中（AIS）的治疗发生了变革。尽管机械取栓术在实现大血管闭塞的高再通率方面取得了成功，但治疗后的功能独立性仍不尽人意。MT目前的局限性促使人们评估辅助药物神经保护疗法在预防AIS期间导致不可逆神经元损伤的兴奋性毒性、细胞凋亡和炎症方面的作用。镁（MgSO）具有多种不同作用，提供了一种有吸引力的神经保护特性，价格低廉、易于获得，并且在心肌梗死和子痫的治疗中具有长期确立的安全性和耐受性。
技术成功与患者预后之间的这种差距很大程度上是由于无法在缺血期间充分保护脑组织免受梗死。MgSO在临床前研究中因其神经保护特性显示出前景，包括阻断NMDA受体、增加脑血流量和稳定离子通道。然而，诸如FAST-MAG和IMAGES等临床试验未能证明静脉注射MgSO有显著益处，原因是药物给药延迟或未能送达靶组织。这些试验凸显了更快、更有针对性给药的必要性。通过MT中使用的导管进行动脉内（IA）注射MgSO可以通过将高剂量药物直接输送到缺血脑组织来解决这些局限性，有可能增强神经保护作用同时减少全身暴露。临床前研究和一些临床试验已经证明了IA给药的安全性和可行性，但未证明IA注射MgSO的安全性和可行性。需要进一步研究以评估其疗效。
虽然过去的试验没有成功，但IA注射像MgSO这样的神经保护剂可能会改善MT术后卒中患者的功能预后。正在进行的和未来的研究将确定这种方法是否能有效补充再灌注策略，有可能开创卒中治疗的新时代。
