Arenillas Juan F, Sobrino Tomás, Castillo José, Dávalos Antoni
Stroke Unit, Department of Neurosciences, Germans Trias University Hospital, Carretera de Canyet s.n., Badalona (Barcelona) 08196, Spain.
Curr Treat Options Cardiovasc Med. 2007 Jun;9(3):205-12. doi: 10.1007/s11936-007-0014-5.
Ischemic stroke is burdened with a high morbidity and mortality in our society. However, there are few effective and largely available therapies for this devastating disease. In additon to advancing acute reperfusion therapies, there is a need to develop treatments aimed to promote repair and regeneration of brain tissue damaged by ischemia (neurorecovery). Therapeutic angiogenesis and vasculogenesis represent novel approaches of regenerative medicine that may help in the cure of patients with acute ischemic stroke. Translation of our knowledge about these processes from the bench to bedside is still underway. Although angiogenesis (the sprouting of new blood vessels from pre-existing vascular structures) is likely to contribute to neurorepair, the finality of the angiogenic response in acute ischemic stroke has not been fully elucidated. The first therapeutic approach to angiogenesis after ischemic stroke would be the modulation of the endogenous angiogenic response. In this setting, early instauration of physical activity, statins, and peroxisome proliferator-activated receptor-gamma agonists may enhance angiogenesis and neuroregeneration. Gene therapy with vascular growth factors has been successfully tested in patients affected by chronic myocardial and peripheral ischemia. Regarding brain ischemia, experiments in animal models have shown that the effect of these growth factors is critically affected by the dosage, route of delivery, and time of administration in relation to stroke onset. In addition, the optimal angiogenic substance is unknown. Finally, vectors for gene transfer should be further optimized. Therapeutic vasculogenesis consists of the administration of exogenous endothelial progenitor cells in order to enhance brain repair processes. Endothelial progenitor cells may be recruited in response to cerebral ischemia and participate in reparative vasculogenesis after acute ischemic stroke. Further research is needed to clarify their role and therapeutic applicability in human brain ischemia.
在我们的社会中,缺血性中风的发病率和死亡率都很高。然而,对于这种毁灭性疾病,几乎没有有效且广泛可用的治疗方法。除了推进急性再灌注治疗外,还需要开发旨在促进缺血损伤的脑组织修复和再生(神经恢复)的治疗方法。治疗性血管生成和血管新生是再生医学的新方法,可能有助于治疗急性缺血性中风患者。将我们对这些过程的认识从实验室转化到临床仍在进行中。虽然血管生成(从预先存在的血管结构中长出新血管)可能有助于神经修复,但急性缺血性中风中血管生成反应的最终结果尚未完全阐明。缺血性中风后血管生成的第一种治疗方法是调节内源性血管生成反应。在这种情况下,早期开始体育活动、使用他汀类药物和过氧化物酶体增殖物激活受体-γ激动剂可能会增强血管生成和神经再生。血管生长因子基因治疗已在慢性心肌和外周缺血患者中成功进行了测试。关于脑缺血,动物模型实验表明,这些生长因子的效果受到剂量、给药途径以及与中风发作相关的给药时间的严重影响。此外,最佳的血管生成物质尚不清楚。最后,基因转移载体应进一步优化。治疗性血管新生包括给予外源性内皮祖细胞以增强脑修复过程。内皮祖细胞可能会因脑缺血而被募集,并参与急性缺血性中风后的修复性血管新生。需要进一步研究以阐明它们在人类脑缺血中的作用和治疗适用性。