Adembri Chiara, Bechi Annalisa, Meli Elena, Gramigni Elena, Venturi Luna, Moroni Flavio, De Gaudio A Raffaele, Pellegrini-Giampietro Domenico E
Dipartimento di Area Critica Medico Chirurgica, Sezione di Anestesiologia e Terapia Intensiva, Università di Firenze, Firenze, Italy.
J Neurotrauma. 2004 Aug;21(8):1103-12. doi: 10.1089/0897715041651079.
Recent experimental evidence indicates that erythropoietin (Epo), in addition to its hormonal role in regulating red cell production, operates as a neuroprotective agent. So far, the neuroprotective effect of human recombinant Epo (rhEpo) has been mainly demonstrated in models of cerebral ischemia/hypoxia and in selected in vivo studies of traumatic neuronal injury. To further investigate the potential role of this multifunctional trophic factor in post-traumatic cell death, we examined the protective effects of rhEpo in a newly developed model of mechanical trauma in organotypic hippocampal slices. Organotypic rat hippocampal slices were subjected to traumatic injury by allowing a stylus to impact on the CA1 area with an energy of 6 microJ. Hippocampal damage was identified and measured 24 and 48 h later with the fluorescent dye propidium iodide (PI). In untreated slices, the impact induced a significant increase in the mean hippocampal PI fluorescence, co-localized with the area of impact at 24 h (primary post-traumatic injury) and progressively spread to the whole slice between 24 and 48 h (secondary post-traumatic injury). Addition of rhEpo (1-100 UI/mL) or of the NMDA antagonist MK-801 (30 microM) immediately after the traumatic injury reduced hippocampal damage by approximately 30% when observed 24 h later. At 48 h after trauma, the protective effect of rhEpo was greater (by about 47%) and significantly more pronounced than that of MK-801 (28%). Our results suggest that the neuroprotective activity of rhEpo is particularly effective against delayed, secondary post-traumatic damage. This well tolerated agent could provide a therapeutic benefit in pathologies involving post-traumatic neurodegeneration.
最近的实验证据表明，促红细胞生成素（Epo）除了在调节红细胞生成方面发挥激素作用外，还作为一种神经保护剂发挥作用。到目前为止，重组人促红细胞生成素（rhEpo）的神经保护作用主要在脑缺血/缺氧模型以及创伤性神经元损伤的特定体内研究中得到证实。为了进一步研究这种多功能营养因子在创伤后细胞死亡中的潜在作用，我们在新建立的器官型海马切片机械创伤模型中检测了rhEpo的保护作用。通过用探针以6微焦耳的能量撞击CA1区域，对器官型大鼠海马切片造成创伤性损伤。在24小时和48小时后，用荧光染料碘化丙啶（PI）识别并测量海马损伤。在未处理的切片中，撞击导致海马PI平均荧光显著增加，在24小时时（创伤后原发性损伤）与撞击区域共定位，并在24至48小时之间逐渐扩散至整个切片（创伤后继发性损伤）。创伤性损伤后立即添加rhEpo（1 - 100 UI/mL）或NMDA拮抗剂MK - 801（30 microM），24小时后观察发现海马损伤减少了约30%。创伤后48小时，rhEpo的保护作用更强（约47%），且比MK - 801（28%）的保护作用明显更显著。我们的结果表明，rhEpo的神经保护活性对延迟性创伤后继发性损伤特别有效。这种耐受性良好的药物可能在涉及创伤后神经退行性变的疾病中提供治疗益处。
