Grasso Giovanni, Buemi Michele, Alafaci Concetta, Sfacteria Alessandra, Passalacqua Marcello, Sturiale Alessio, Calapai Gioacchino, De Vico Gionata, Piedimonte Giuseppe, Salpietro Francesco M, Tomasello Francesco
Department of Neurosurgery, University of Messina, 98122 Messina, Italy.
Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5627-31. doi: 10.1073/pnas.082097299. Epub 2002 Apr 9.
Cerebral vasospasm and ischemic damage are important causes of mortality and morbidity in patients affected by aneurysmal subarachnoid hemorrhage (SAH). Recently, i.p. administration of recombinant human erythropoietin (r-Hu-EPO) has been shown to exert a neuroprotective effect during experimental SAH. The present study was conducted to evaluate further the effect of r-Hu-EPO administration after SAH in rabbits on neurological outcome, degree of basilar artery spasm, and magnitude of neuronal ischemic damage. Experimental animals were divided into six groups: group 1 (n = 8), control; group 2 (n = 8), control plus placebo; group 3 (n = 8), control plus r-Hu-EPO; group 4 (n = 8), SAH; group 5 (n = 8), SAH plus placebo; group 6 (n = 8), SAH plus r-Hu-EPO. r-Hu-EPO, at a dose of 1,000 units/kg, and placebo were injected i.p. starting 5 min after inducing SAH and followed by clinical and pathological assessment 72 h later. Systemic administration of r-Hu-EPO produced significant increases in cerebrospinal fluid EPO concentrations (P < 0.001), and reduced vasoconstriction of the basilar artery (P < 0.05), ischemic neuronal damage (P < 0.001), and subsequent neurological deterioration (P < 0.05). These observations suggest that r-Hu-EPO may provide an effective treatment to reduce the post-SAH morbidity.
脑血管痉挛和缺血性损伤是动脉瘤性蛛网膜下腔出血(SAH)患者死亡和发病的重要原因。最近,已证明腹腔注射重组人促红细胞生成素(r-Hu-EPO)在实验性SAH期间发挥神经保护作用。本研究旨在进一步评估SAH后给兔注射r-Hu-EPO对神经功能结局、基底动脉痉挛程度和神经元缺血性损伤程度的影响。实验动物分为六组:第1组(n = 8),对照组;第2组(n = 8),对照组加安慰剂;第3组(n = 8),对照组加r-Hu-EPO;第4组(n = 8),SAH组;第5组(n = 8),SAH加安慰剂组;第6组(n = 8),SAH加r-Hu-EPO组。在诱导SAH后5分钟开始腹腔注射剂量为1000单位/千克的r-Hu-EPO和安慰剂,72小时后进行临床和病理评估。全身给予r-Hu-EPO可使脑脊液EPO浓度显著升高(P < 0.001),并减轻基底动脉血管收缩(P < 0.05)、缺血性神经元损伤(P < 0.001)和随后的神经功能恶化(P < 0.05)。这些观察结果表明,r-Hu-EPO可能提供一种有效的治疗方法来降低SAH后的发病率。