Verdonck Olivier, Lahrech Hana, Francony Gilles, Carle Olivier, Farion Régine, Van de Looij Yohan, Remy Chantal, Segebarth Christoph, Payen Jean-Francois
INSERM, U594, Grenoble, France.
J Cereb Blood Flow Metab. 2007 Jul;27(7):1369-76. doi: 10.1038/sj.jcbfm.9600443. Epub 2007 Jan 31.
Erythropoietin (Epo) is gaining interest in various neurological insults as a possible neuroprotective agent. We determined the effects of recombinant human Epo (rhEpo, 5000 IU per kg bw) on brain edema induced in rats by traumatic brain injury (TBI; impact-acceleration model; rhEpo administration 30 mins after injury). Magnetic resonance imaging (MRI) and a gravimetric technique were applied. In the MRI experiments, the apparent diffusion coefficient (ADC) and the tissue T(1) relaxation time were measured hourly in the neocortex and caudoputamen, during a 6 h time span after TBI. In the gravimetric experiments, brain water content (BWC) was determined in these two regions, 6 h after TBI. Apparent diffusion coefficient measurements showed that rhEpo decreased brain edema early and durably. Gravimetric measurements showed that rhEpo decreased BWC at H(6) in the neocortex as well as in the caudoputamen. No significant differences in ADC, in T(1), or in BWC were found between rhEpo treated-TBI rats and sham-operated rats. Our findings show that post-traumatic administration of rhEpo can significantly reduce the development of brain edema in a model of diffuse TBI. Further studies should be conducted to identify the biochemical mechanisms involved in these immediate effects and to assess the use of rhEpo as a possible therapy for post-traumatic brain edema.
促红细胞生成素(Epo)作为一种可能的神经保护剂,在各种神经损伤中受到越来越多的关注。我们确定了重组人促红细胞生成素(rhEpo,每千克体重5000国际单位)对创伤性脑损伤(TBI;撞击-加速模型;伤后30分钟给予rhEpo)诱导的大鼠脑水肿的影响。应用了磁共振成像(MRI)和重量法技术。在MRI实验中,在TBI后的6小时内,每小时测量新皮层和尾壳核的表观扩散系数(ADC)和组织T(1)弛豫时间。在重量法实验中,在TBI后6小时测定这两个区域的脑含水量(BWC)。表观扩散系数测量表明,rhEpo能早期且持久地减轻脑水肿。重量法测量表明,rhEpo能降低新皮层和尾壳核在6小时时的BWC。在rhEpo治疗的TBI大鼠和假手术大鼠之间,未发现ADC、T(1)或BWC有显著差异。我们的研究结果表明,创伤后给予rhEpo可在弥漫性TBI模型中显著减少脑水肿的发展。应进一步开展研究,以确定这些即时效应所涉及的生化机制,并评估rhEpo作为创伤后脑水肿可能治疗方法的应用。