NEUROPROTECTIVE EFFECT OF ERYTHROPOIETIN AND DARBEPOETIN ALFA AFTER EXPERIMENTAL INTRACEREBRAL HEMORRHAGE
NEUROPROTECTIVE EFFECT OF ERYTHROPOIETIN AND DARBEPOETIN ALFA AFTER EXPERIMENTAL INTRACEREBRAL HEMORRHAGE
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DOI：
10.1227/01.neu.0000347475.73347.5f
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发表时间：
2009-10-01
期刊：
影响因子：
4.8
通讯作者：
Iacopino, Domenico Gerardo
中科院分区：
文献类型：
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作者：
Grasso, Giovanni;Graziano, Francesca;Iacopino, Domenico Gerardo
目的：脑出血（ICH）是一种毁灭性的临床综合征，目前还没有真正有效的治疗方法。在临床前研究中，促红细胞生成素（EPO）及其长效类似物达贝泊素α已被证明在几种神经元损伤模型中具有神经保护作用。本研究的目的是分析是否重组人促红细胞生成素（rHuEPO）和其持久的衍生物达贝泊素阿尔法的全身给药加快功能恢复和脑损伤的大鼠模型ICH.METHODS：实验性脑出血诱导大鼠通过注射自体血到右纹状体立体定向指导下。随后，动物接受安慰剂治疗，每日注射rHuEPO，或每周注射达贝泊汀α。动物被杀14 days after injury.RESULTS：无论是rHuEPO和darbeposterone alfa是有效的，在减少损伤后的神经功能缺损，进行评估的神经功能的任务。rHuEPO和darbepoposidin α治疗的动物表现出限制性脑损伤，实质结构几乎正常。相比之下，盐水处理组表现出广泛的脑细胞结构破坏和水肿。结论：每周给予达贝泊苷α对大鼠脑出血后行为学和组织学的神经保护作用与每日给予EPO相似。EPO及其长效重组形式的给药在ICH模型中提供了显着的神经保护作用，并可能为未来的临床应用带来希望。
OBJECTIVE: Intracerebral hemorrhage (ICH) is a devastating clinical syndrome for which no truly efficacious therapy has yet been identified. In preclinical studies, erythropoietin (EPO) and its long-lasting analog, darbepoetin alfa, have been demonstrated to be neuroprotective in several models of neuronal insult. The objectives of this study were to analyze whether the systemic administration of recombinant human EPO (rHuEPO) and its long-lasting derivative darbepoetin alfa expedited functional recovery and brain damage in a rat model of ICH.METHODS: Experimental ICH was induced in rats by injecting autologous blood into the right striatum under stereotactic guidance. Subsequently, animals underwent placebo treatment, daily injections of rHuEPO, or weekly injections of darbepoetin alfa. Animals were killed 14 days after injury.RESULTS: Both rHuEPO and darbepoetin alfa were effective in reducing neurological impairment after injury, as assessed by the neurological tasks performed. rHuEPO- and darbepoetin alfa-treated animals exhibited a restricted brain injury with nearly normal parenchymal architecture. In contrast, the saline-treated group exhibited extensive cerebral cytoarchitectural disruption and edema. The number of surviving NeuN-positive neurons was significantly higher in the rats treated with rHuEPO and darbepoetin alfa compared with those that received saline (P < 0.05).CONCLUSION: These results demonstrate that weekly administered darbepoetin alfa confers behavioral and histological neuroprotection after ICH in rats similar to that of daily EPO administration. Administration of EPO and its long-lasting recombinant forms affords significant neuroprotection in an ICH model and may hold promise for future clinical applications.