Abstract
Subarachnoid hemorrhage (SAH) following aneurysm bleeding accounts for 6% to 8% of all cerebrovascular accidents. Although an aneurysm can be effectively managed by surgery or endovascular therapy, delayed cerebral ischemia is diagnosed in a high percentage of patients resulting in significant morbidity and mortality. Cerebral vasospasm occurs in more than half of all patients after aneurysm rupture and is recognized as the leading cause of delayed cerebral ischemia after SAH. Hemodynamic strategies and endovascular procedures may be considered for the treatment of cerebral vasospasm. In recent years, the mechanisms contributing to the development of vasospasm, abnormal reactivity of cerebral arteries and cerebral ischemia following SAH, have been investigated intensively. A number of pathological processes have been identified in the pathogenesis of vasospasm, including endothelial injury, smooth muscle cell contraction from spasmogenic substances produced by the subarachnoid blood clots, changes in vascular responsiveness and inflammatory response of the vascular endothelium. To date, the current therapeutic interventions remain ineffective as they are limited to the manipulation of systemic blood pressure, variation of blood volume and viscosity and control of arterial carbon dioxide tension. In this scenario, the hormone erythropoietin (EPO) has been found to exert neuroprotective action during experimental SAH when its recombinant form (rHuEPO) is administered systemically. However, recent translation of experimental data into clinical trials has suggested an unclear role of recombinant human EPO in the setting of SAH. In this context, the aim of the current review is to present current evidence on the potential role of EPO in cerebrovascular dysfunction following aneurysmal subarachnoid hemorrhage.
Highlights
Cerebral vasoconstriction following aneurysmal subarachnoid hemorrhage (SAH) can produce cerebral ischemia, neurological disability and premature death
It is well known that cerebral arteries respond to SAH with a biphasic contraction: an acute vasoconstriction that begins minutes following the bleeding and a delayed vasospasm that occurs more than 48 h later [1,2]
Many studies have extensively identified the delayed vasospasm as the major complication in patients affected by aneurysmal SAH, the physiopathological and clinical importance of acute vasoconstriction, a phenomenon well documented in experimental settings [1], remains to be elucidated in humans
Summary
Cerebral vasoconstriction following aneurysmal subarachnoid hemorrhage (SAH) can produce cerebral ischemia, neurological disability and premature death. A single EPO molecule binds to two assembled receptor units on the cell surface, and tyrosines located in the intracellular domain are phosphorylated This process triggers an intracellular signaling cascade that regulates gene expression in the nucleus, which in turn controls cell survival, proliferation and differentiation [13]. The hematopoietic and tissue-protective activities could be separated occurring the hormonal and neuroprotective actions of EPO via a different signaling systems [32] Based on this information, engineered molecules have been developed that mediate tissue protection but do not bind to erythroid progenitors, thereby dissociating the biology of EPO- mediated cytoprotection from that of erythropoiesis [32,33]
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