Xiong Ye, Mahmood Asim, Lu Dunyue, Qu Changsheng, Goussev Anton, Schallert Timothy, Chopp Michael
Department of Neurosurgery, Henry Ford Health System, 2799 West Grand Boulevard, Detroit, MI 48202, USA.
Brain Res. 2007 Dec 14;1185:301-12. doi: 10.1016/j.brainres.2007.09.052. Epub 2007 Oct 31.
The aim of this study was to investigate the role of gender in histological and functional outcome, angiogenesis, neurogenesis and therapeutic effects of recombinant human erythropoietin (rhEPO) in mice after traumatic brain injury (TBI). TBI caused both tissue loss in the cortex and cell loss in the dentate gyrus (DG) in the injured hemisphere at day 35 post TBI without a significant gender difference. After TBI, sensorimotor deficits were significantly larger in male mice compared to females, while similar spatial learning deficits were present in both genders. TBI alone significantly stimulated angiogenesis and neurogenesis in the cortex and in the DG of injured hemispheres in both genders. rhEPO at a dose of 5000 units/kg body weight administered intraperitoneally at 6 h, and 3 and 7 days after injury significantly reduced lesion volume and DG cell loss examined at day 35 after TBI as well as dramatically improved sensorimotor and spatial learning performance without an obvious gender proclivity. rhEPO significantly enhanced neurogenesis in the cortex and the DG of the ipsilateral hemisphere in male TBI mice. rhEPO did not affect angiogenesis in the ipsilateral cortex and DG in both genders after TBI. The present data demonstrate that posttraumatic administration of rhEPO improves histological and functional outcome in both genders, which may be mediated by reducing cortical tissue damage and DG cell loss in the ipsilateral hemisphere. In addition, the major gender propensity observed in the present study with mice after TBI without treatment is limited to sensorimotor deficits and cell proliferation.
本研究旨在探讨性别在创伤性脑损伤（TBI）后小鼠的组织学和功能结局、血管生成、神经发生以及重组人促红细胞生成素（rhEPO）治疗效果中的作用。在TBI后35天，TBI导致损伤半球的皮质组织损失和齿状回（DG）细胞损失，且无显著性别差异。TBI后，雄性小鼠的感觉运动功能障碍比雌性小鼠更显著，而两性均存在相似的空间学习功能障碍。单纯TBI显著刺激了两性损伤半球皮质和DG中的血管生成和神经发生。在损伤后6小时、3天和7天腹腔注射剂量为5000单位/千克体重的rhEPO，可显著减少TBI后35天检测到的损伤体积和DG细胞损失，并显著改善感觉运动和空间学习表现，且无明显性别倾向。rhEPO显著增强了雄性TBI小鼠同侧半球皮质和DG中的神经发生。TBI后，rhEPO对两性同侧皮质和DG中的血管生成均无影响。目前的数据表明，创伤后给予rhEPO可改善两性的组织学和功能结局，这可能是通过减少同侧半球的皮质组织损伤和DG细胞损失来介导的。此外，本研究在未治疗的TBI小鼠中观察到的主要性别倾向仅限于感觉运动功能障碍和细胞增殖。
