Grasso Giovanni
Department of Neurosurgery, University of Messina, Via C. Valeria 1, 98122, Messina, Italy.
Brain Res Brain Res Rev. 2004 Jan;44(1):49-63. doi: 10.1016/j.brainresrev.2003.10.003.
Cerebral vasospasm and the resulting cerebral ischemia occurring after subarachnoid hemorrhage (SAH) are still responsible for the considerable morbidity and mortality in patients affected by cerebral aneurysms. Mechanisms contributing to the development of vasospasm, abnormal reactivity of cerebral arteries and cerebral ischemia after SAH have been intensively investigated in recent years. It has been suggested that the pathogenesis of vasospasm is related to a number of pathological processes, including endothelial damage, smooth muscle cell contraction resulting from spasmogenic substances generated during lyses of subarachnoid blood clots, changes in vascular responsiveness and inflammatory or immunological reactions of the vascular wall. A great deal of experimental and clinical research has been conducted in an effort to find ways to prevent these complications. However, to date, the main therapeutic interventions remain elusive and are limited to the manipulation of systemic blood pressure, alteration of blood volume or viscosity, and control of arterial dioxide tension. Even though no single pharmacological agent or treatment protocol has been identified which could prevent or reverse these deadly complications, a number of promising drugs have been investigated. Among these is the hormone erythropoietin (EPO), the main regulator of erythropoiesis. It has recently been found that EPO produces a neuroprotective action during experimental SAH when its recombinant form (rHuEPO) is systemically administered. This topic review collects the relevant literature on the main investigative therapies for cerebrovascular dysfunction after aneurysmal SAH. In addition, it points out rHuEPO, which may hold promise in future clinical trials to prevent the occurrence of vasospasm and cerebral ischemia after SAH.
蛛网膜下腔出血（SAH）后发生的脑血管痉挛及由此导致的脑缺血，仍是影响脑动脉瘤患者发病率和死亡率的重要因素。近年来，人们对SAH后血管痉挛的发生机制、脑动脉异常反应性及脑缺血进行了深入研究。有研究表明，血管痉挛的发病机制与多种病理过程有关，包括内皮损伤、蛛网膜下腔血凝块溶解过程中产生的致痉物质引起的平滑肌细胞收缩、血管反应性改变以及血管壁的炎症或免疫反应。为寻找预防这些并发症的方法，人们进行了大量的实验和临床研究。然而，迄今为止，主要的治疗干预措施仍不明确，仅限于调节全身血压、改变血容量或血液粘度以及控制动脉二氧化碳分压。尽管尚未确定能预防或逆转这些致命并发症的单一药物或治疗方案，但已对一些有前景的药物进行了研究。其中包括激素促红细胞生成素（EPO），它是红细胞生成的主要调节因子。最近发现，在实验性SAH期间，全身给予重组促红细胞生成素（rHuEPO）时，EPO具有神经保护作用。本专题综述收集了有关动脉瘤性SAH后脑血管功能障碍主要研究性治疗方法的相关文献。此外，还指出了rHuEPO，它可能在未来的临床试验中有望预防SAH后血管痉挛和脑缺血的发生。
