Basile A M, Nencini P, Inzitari D
Clinica Neurologica III, Università degli Studi di Firenze.
Ann Ital Med Int. 1999 Apr-Jun;14(2):94-105.
Therapeutic interventions for acute ischemic stroke have not yet been established in clinical practice. The recognition of an area of reduced blood flow in which neuronal death may be prevented has focused attention on treatments aiming at minimizing ischemic brain damage, if they are initiated within short time after occlusion. The combination of restoring blood flow and providing neuroprotection may be the most productive approach in human acute ischemic stroke, but this combined therapy requires testing through clinical trials. To gain insight into the molecular mechanisms of cerebral ischemia, this review examines the excito-toxic cascade, synthesis and role of nitric oxide and oxidants, gene regulation and possible neuroprotective therapeutic targets. As neuroprotectants, glutamate-antagonists, calcium-antagonists and free radical scavengers have been investigated. The role of nitric oxide is very complex, as it can be cytotoxic or cytoprotective in relation to sources, time of synthesis, and medium redox state. Animal gene studies suggest that nitric oxide produced by endothelial nitric oxide synthase may be advantageous, while nitric oxide produced by neuronal and inducible nitric oxide synthase disadvantageous. A treatment strategy could involve the use of selective inhibitors of different types of nitric oxide synthase. Cell death after cerebral ischemia occurs through the dual pathway of ischemic necrosis and apoptosis. Novel therapies may be directed at genes mediating either recovery or apoptosis. There are, as yet, no conclusive data concerning the safety and efficacy of neuroprotectants in humans. Differences between animal models and clinical conditions may justify the discrepancy between experimental data and clinical practice.
急性缺血性中风的治疗干预措施在临床实践中尚未确立。识别出可能预防神经元死亡的血流减少区域，使得人们将注意力集中在旨在在闭塞后短时间内启动以最小化缺血性脑损伤的治疗方法上。恢复血流和提供神经保护的联合疗法可能是治疗人类急性缺血性中风最有效的方法，但这种联合疗法需要通过临床试验进行验证。为了深入了解脑缺血的分子机制，本综述研究了兴奋性毒性级联反应、一氧化氮和氧化剂的合成及作用、基因调控以及可能的神经保护治疗靶点。作为神经保护剂，人们已经研究了谷氨酸拮抗剂、钙拮抗剂和自由基清除剂。一氧化氮的作用非常复杂，因为根据来源、合成时间和介质氧化还原状态，它可能具有细胞毒性或细胞保护作用。动物基因研究表明，内皮型一氧化氮合酶产生的一氧化氮可能具有优势，而神经元型和诱导型一氧化氮合酶产生的一氧化氮则具有劣势。一种治疗策略可能涉及使用不同类型一氧化氮合酶的选择性抑制剂。脑缺血后的细胞死亡通过缺血性坏死和凋亡的双重途径发生。新的疗法可能针对介导恢复或凋亡的基因。目前，关于神经保护剂在人类中的安全性和有效性尚无确凿数据。动物模型与临床情况之间的差异可能解释了实验数据与临床实践之间的差异。
