Seyfried D M, Han Y, Yang D, Ding J, Chopp M
Department of Neurosurgery, Henry Ford Health System, Detroit, MI 48202, USA.
Int J Stroke. 2009 Aug;4(4):250-6. doi: 10.1111/j.1747-4949.2009.00292.x.
Attention has turned to neurorestorative therapies, including erythropoietin, for experimental ischaemic stroke and head injury. Treatments for intracerebral haemorrhage need to be developed, as this represents a particularly devastating and common form of neurological injury. Aim The aim of this study is to investigate the therapeutic potential of erythropoietin after intracerebral haemorrhage in rats and to measure its effects on mechanisms of recovery and neurogenesis.
Intracerebral haemorrhage was induced in 24 Wistar male rats by intrastriatal infusion of autologous blood. Recombinant human erythropoietin (5000 or 10,000 U/kg BW/day) or saline was administered starting 1 day after intracerebral haemorrhage and continued daily for 1 week (n=8 for each group). To label proliferating cells, 5'-bromo-2' deoxyuridine was injected daily for 13 days after intracerebral haemorrhage. All animals survived for 2 weeks after intracerebral haemorrhage. Functional outcome, area of tissue loss and immunohistochemical staining were measured at 14 days after intracerebral haemorrhage. Global test or anova was used to test the erythropoietin dose effect.
Rats receiving recombinant human erythropoietin after intracerebral haemorrhage exhibited significant improvement in modified neurological severity score and corner test at 14 days (P<0.05). Increased expression of phenotypes of synaptogenesis and proliferating immature neurons were shown by immunohistochemical staining. Only the group receiving a lower dose of recombinant human erythropoietin had significantly less tissue loss compared with the control group (P<0.05). In rats treated with recombinant human erythropoietin, double staining for 5'-bromo-2' deoxyuridine and TUJ1 revealed a subpopulation of cells that express an immature neuronal marker while still dividing.
Erythropoietin improves neurological outcome and increases histochemical parameters of neurogenesis when given after intracerebral haemorrhage in rats. Intriguingly, only the lower dose of recombinant human erythropoietin was effective in reducing tissue loss in the region of intracerebral haemorrhage.
对于实验性缺血性中风和头部损伤，人们的注意力已转向神经修复疗法，包括促红细胞生成素。由于脑出血是一种特别具有破坏性且常见的神经损伤形式，因此需要开发针对脑出血的治疗方法。目的本研究旨在探讨促红细胞生成素对大鼠脑出血后的治疗潜力，并测量其对恢复机制和神经发生的影响。
通过向纹状体内注入自体血，在24只雄性Wistar大鼠中诱导脑出血。在脑出血后1天开始给予重组人促红细胞生成素（5000或10000 U/kg体重/天）或生理盐水，持续每日给药1周（每组n = 8）。为标记增殖细胞，在脑出血后连续13天每日注射5'-溴-2'-脱氧尿苷。所有动物在脑出血后存活2周。在脑出血后14天测量功能结局、组织损失面积和免疫组织化学染色。使用全局检验或方差分析来测试促红细胞生成素的剂量效应。
脑出血后接受重组人促红细胞生成素的大鼠在14天时改良神经功能缺损评分和转角试验有显著改善（P < 0.05）。免疫组织化学染色显示突触形成和增殖未成熟神经元的表型表达增加。与对照组相比，只有接受较低剂量重组人促红细胞生成素的组组织损失显著减少（P < 0.05）。在用重组人促红细胞生成素治疗的大鼠中，5'-溴-2'-脱氧尿苷和TUJ1的双重染色显示出一群细胞，这些细胞在仍在分裂时表达未成熟神经元标记物。
促红细胞生成素在大鼠脑出血后给予时可改善神经功能结局并增加神经发生的组织化学参数。有趣的是，只有较低剂量的重组人促红细胞生成素在减少脑出血区域的组织损失方面有效。
