Erythropoietin promotes neurovascular remodeling and long-term functional recovery in rats following traumatic brain injury.

Erythropoietin promotes neurovascular remodeling and long-term functional recovery in rats following traumatic brain injury.
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DOI:
10.1016/j.brainres.2011.01.099
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发表时间:
2011-04-12
期刊:
影响因子:
2.9
通讯作者:
Chopp M
Chopp M
中科院分区:
医学3区
文献类型:
--
作者:
Ning R;Xiong Y;Mahmood A;Zhang Y;Meng Y;Qu C;Chopp M

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促红细胞生成素 (EPO) 可改善创伤性脑损伤 (TBI) 后的功能恢复。本研究旨在调查 EPO 对 TBI 后大鼠大脑重塑和功能恢复的长期(3 个月)影响。年轻雄性 Wistar 大鼠受到单侧控制性皮质冲击损伤。 TBI大鼠分为以下组:1)盐水组(n = 7); 2) EPO-6h组(n=8); 3) EPO-24h 组 (n = 8)。损伤后6小时、1天和2天(EPO-6h组)或1、2和3天(EPO-24h组)腹腔注射EPO(5,000 U/kg生理盐水)。使用改良的神经严重程度评分、失误和莫里斯水迷宫测试来评估神经功能。受伤后3个月处死动物,并对脑切片进行染色以进行免疫组织化学分析。与生理盐水相比,EPO-6h治疗显着减少了皮质病灶体积,而EPO-24h治疗对病灶体积没有影响(P<0.05)。与盐水对照组相比,EPO-6h和EPO-24h治疗均显着减少海马细胞损失(P<0.05),促进血管生成(P<0.05)并增加损伤边界区和海马内源性细胞增殖(BrdU阳性细胞)(P<0.05)。与盐水组相比,EPO 组的齿状回神经发生(BrdU/NeuN 阳性细胞)显着增强。两种 EPO 治疗均显着改善了 TBI 后的长期感觉运动和认知功能恢复。总之,创伤后 EPO 治疗对受伤大脑的有益效果可持续至少 3 个月。功能结果的长期改善可能部分与 EPO 诱导的神经血管重塑有关。
Erythropoietin (EPO) improves functional recovery after traumatic brain injury (TBI). This study was designed to investigate long-term (3 mo) effects of EPO on brain remodeling and functional recovery in rats after TBI. Young male Wistar rats were subjected to unilateral controlled cortical impact injury. TBI rats were divided into the following groups: 1) Saline group (n = 7); 2) EPO-6h group (n = 8); and 3) EPO-24h group (n = 8). EPO (5,000 U/kg in saline) was administered intraperitoneally at 6 h, and 1 and 2 days (EPO-6h group) or at 1, 2, and 3 days (EPO-24h group) post injury. Neurological function was assessed using a modified neurological severity score, footfault and Morris water maze tests. Animals were sacrificed at 3 mos after injury and brain sections stained for immunohistochemical analyses. Compared to the saline, EPO-6h treatment significantly reduced cortical lesion volume, while EPO-24h therapy did not affect the lesion volume (P<0.05). Both the EPO-6h and EPO-24h treatments significantly reduced hippocampal cell loss (P<0.05), promoted angiogenesis (P<0.05) and increased endogenous cellular proliferation (BrdU-positive cells) in the injury boundary zone and hippocampus (P<0.05) compared to saline controls. Significantly enhanced neurogenesis (BrdU/NeuN-positive cells) was seen in the dentate gyrus of both EPO groups compared to the saline group. Both EPO treatments significantly improved long-term sensorimotor and cognitive functional recovery after TBI. In conclusion, the beneficial effects of posttraumatic EPO treatment on injured brain persisted for at least 3 months. The long-term improvement in functional outcome may in part be related to the neurovascular remodeling induced by EPO.
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