Alraddadi Eman A, Aljuhani Faisal F, Alsamiri Ghadah Y, Hafez Salwa Y, Alselami Ghaida, Almarghalani Daniyah A, Alamri Faisal F
Department of Basic Sciences, College of Science and Health Professions, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia.
King Abdullah International Medical Research Center, Jeddah, Saudi Arabia.
J Neuroimmune Pharmacol. 2025 Feb 3;20(1):12. doi: 10.1007/s11481-025-10171-z.
Stroke represents a significant burden on global health and the economy, with high mortality rates, disability, and recurrence. Ischemic stroke is a serious condition that occurs when a blood vessel in the brain is interrupted, reducing the blood supply to the affected area. Inflammation is a significant component in stroke pathophysiology. Neuroinflammation is triggered following the acute ischemic ictus, where the blood-brain barrier (BBB) breaks down, causing damage to the endothelial cells. The damage will eventually generate oxidative stress, activate the pathological phenotypes of astrocytes and microglia, and lead to neuronal death in the neurovascular unit. As a result, the brain unleashes a robust neuroinflammatory response, which can further worsen the neurological outcomes. Neuroinflammation is a complex pathological process involved in ischemic damage and repair. Finding new neuroinflammation molecular targets is essential to develop effective and safe novel treatment approaches against ischemic stroke. Accumulating studies have investigated the pharmacological properties of cannabinoids (CBs) for many years, and recent research has shown their potential therapeutic use in treating ischemic stroke in rodent models. These findings revealed promising impacts of CBs in reducing neuroinflammation and cellular death and ameliorating neurological deficits. In this review, we explore the possibility of the therapeutic administration of CBs in mitigating neuroinflammation caused by a stroke. We summarize the results from several preclinical studies evaluating the efficacy of CBs anti-inflammatory interventions in ischemic stroke. Although convincing preclinical evidence implies that CBs targeting neuroinflammation are promising for ischemic stroke, translating these findings into the clinical setting has proven to be challenging. The translation hurdle is due to the essence of the CBs ability to cause anxiety, cognitive deficit, and psychosis. Future studies are warranted to address the dose-beneficial effect of CBs in clinical trials of ischemic stroke-related neuroinflammation treatment.
中风给全球健康和经济带来了巨大负担，具有高死亡率、致残率和复发率。缺血性中风是一种严重病症，发生于脑血管中断时，导致受影响区域的血液供应减少。炎症是中风病理生理学的一个重要组成部分。急性缺血性发作后会引发神经炎症，此时血脑屏障（BBB）会瓦解，导致内皮细胞受损。这种损伤最终会产生氧化应激，激活星形胶质细胞和小胶质细胞的病理表型，并导致神经血管单元中的神经元死亡。结果，大脑会引发强烈的神经炎症反应，这会进一步恶化神经学预后。神经炎症是一个涉及缺血性损伤和修复的复杂病理过程。寻找新的神经炎症分子靶点对于开发针对缺血性中风的有效且安全的新型治疗方法至关重要。多年来，越来越多的研究调查了大麻素（CBs）的药理特性，最近的研究表明它们在治疗啮齿动物模型的缺血性中风方面具有潜在的治疗用途。这些发现揭示了CBs在减轻神经炎症、细胞死亡和改善神经功能缺损方面的有前景的影响。在这篇综述中，我们探讨了治疗性给予CBs以减轻中风引起的神经炎症的可能性。我们总结了几项临床前研究的结果，这些研究评估了CBs抗炎干预在缺血性中风中的疗效。尽管有说服力的临床前证据表明，针对神经炎症的CBs对缺血性中风有前景，但将这些发现转化为临床应用已被证明具有挑战性。转化障碍归因于CBs会导致焦虑、认知缺陷和精神病的本质。未来的研究有必要解决CBs在缺血性中风相关神经炎症治疗的临床试验中的剂量-有益效果问题。
