Treatment of traumatic brain injury with a combination therapy of marrow stromal cells and atorvastatin in rats
Treatment of traumatic brain injury with a combination therapy of marrow stromal cells and atorvastatin in rats
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DOI：
10.1227/01.neu.0000255346.25959.99
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发表时间：
2007-03-01
期刊：
影响因子：
4.8
通讯作者：
Chopp, Michael
中科院分区：
文献类型：
--
作者：
Mahmood, Asim;Lu, Dunyue;Chopp, Michael
目的：本研究探讨了骨髓基质细胞（MSCs）和他汀类药物（阿托伐他汀）联合治疗大鼠创伤性脑损伤后的效果。方法：32只雌性Wistar大鼠通过控制性皮质撞击造成损伤，分为4组。I组在创伤性脑损伤后24小时静脉注射MSC（1 × 10（6））。组II在创伤性脑损伤后24小时开始口服阿托伐他汀（0.5 mg/kg），持续14天。第III组接受MSC（1 × 10（6））与阿托伐他汀（0.5 mg/kg）组合。第IV组（对照组）注射生理盐水。从雄性大鼠的骨髓中收获MSC，以通过Y染色体定位来鉴定雌性受体动物中的雄性供体细胞。功能分析采用改良的神经系统严重程度评分和Morris水迷宫试验。在损伤后35天处死动物，脑切片染色。结果：在单独用MSC或阿托伐他汀治疗的动物中没有观察到功能改善（组I和组II）。然而，在接受联合治疗的动物（第III 1组）中，两种测试模式（改良神经系统严重程度评分和Morris水迷宫）均观察到功能改善。显微镜分析显示，接受联合治疗的动物中存在的MSC显著多于单独接受MSC的动物。此外，显着更多的内源性细胞增殖被认为是在海马和损伤边界区的联合治疗组比在单一疗法或control groups.CONCLUSION：当与间充质干细胞联合给药时，阿托伐他汀增加MSC访问和/或存活在受伤的大脑，并增强功能恢复与单一疗法相比。
OBJECTIVE: This study investigated the effects of a combination therapy of marrow stromal cells (MSCs) and statins (atorvastatin) after traumatic brain injury in rats.METHODS: Thirty-two female Wistar rats were injured by controlled cortical impact and divided into four groups. Group I was injected with MSCs (1 x 10(6)) intravenously 24 hrs after traumatic brain injury. Group II was administered atorvastatin (0.5 mg/kg) orally for 14 days starting 24 hours after traumatic brain injury. Group III received MSCs (1 x 10(6)) combined with atorvastatin (0.5 mg/kg). Group IV (control) was injected with saline. MSCs were harvested from the bone marrow of male rats to identify male donor cells within female recipient animals by localization of Y chromosomes. Functional analysis was performed using modified neurological severity scores and the Morris water maze test. Animals were sacrificed 35 days after injury and brain sections stained withRESULTS: No functional improvement was seen in animals treated with MSCs or atorvastatin alone (Groups I and II). However, functional improvement was seen with both testing modalities (modified neurological severity scores and Morris water maze) in animals receiving combination therapy (Group III1). Microscopic analysis showed that significantly more MSCs were present in animals receiving combination therapy than in those receiving MSCs alone. Also, significantly more endogenous cellular proliferation was seen in the hippocampus and injury boundary zone of the combination therapy group than in the monotherapy or control groups.CONCLUSION: When administered in combination with MSCs, atorvastatin increases MSC access and/or survival within the injured brain and enhances functional recovery compared with monotherapy.