Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Exp Parasitol. 2011 Feb;127(2):500-5. doi: 10.1016/j.exppara.2010.09.010. Epub 2010 Oct 30.
Cerebral malaria (CM) causes substantial mortality and neurological sequelae in survivors, and no neuroprotective regimens are currently available for this condition. Erythropoietin (EPO) reduces neuropathology and improves survival in murine CM. Using the Plasmodium berghei model of CM, we investigated if EPO's neuroprotective effects include activation of endogenous neural stem cells (NSC). By using immunohistochemical markers of different NSC maturation stages, we show that EPO increased the number of nestin(+) cells in the dentate gyrus and in the sub-ventricular zone of the lateral ventricles, relative to control-treatment. 75% of the EPO-treated CM mice displayed migration as nestin(+) NSC. The NSC showed differentiation towards a neural cell lineage as shown by PSA-NCAM binding and NSC maturation and lineage commitment was significantly affected by exogenous EPO and by CM in the sub ventricular zone. These results indicate a rapid, EPO-dependent activation of NSC during CM pathology.
脑型疟疾（CM）可导致大量患者死亡和神经系统后遗症，目前尚无针对该疾病的神经保护方案。促红细胞生成素（EPO）可减轻脑型疟疾病鼠的神经病理学损伤并提高其存活率。本研究使用伯氏疟原虫诱导的脑型疟模型，探究了 EPO 的神经保护作用是否包括激活内源性神经干细胞（NSC）。通过使用不同 NSC 成熟阶段的免疫组织化学标志物，我们发现 EPO 可增加海马齿状回和侧脑室下区的巢蛋白（nestin）阳性细胞数量，与对照组相比有所增加。75%的 EPO 治疗的脑型疟小鼠出现巢蛋白阳性 NSC 迁移。PSA-NCAM 结合实验表明，NSC 向神经细胞谱系分化，而 EPO 外源性和脑型疟在侧脑室下区均可显著影响 NSC 的成熟和谱系分化。这些结果表明，在脑型疟发病过程中存在一种快速的、依赖 EPO 的 NSC 激活作用。
