Intravenous Multipotent Adult Progenitor Cell Therapy Attenuates Activated Microglial/Macrophage Response and Improves Spatial Learning After Traumatic Brain Injury
Intravenous Multipotent Adult Progenitor Cell Therapy Attenuates Activated Microglial/Macrophage Response and Improves Spatial Learning After Traumatic Brain Injury
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DOI：
10.5966/sctm.2013-0100
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发表时间：
2013-12-01
影响因子：
6
通讯作者：
Cox, Charles S., Jr.
中科院分区：
文献类型：
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作者：
Bedi, Supinder S.;Hetz, Robert;Cox, Charles S., Jr.
我们以前证明了啮齿动物创伤性脑损伤（TBI）后静脉内递送多能成体祖细胞（MAPC）通过在细胞治疗后的急性时间范围内保护血脑屏障和全身减轻炎症来提供神经保护;然而，TBI后MAPC给药的长期行为和抗炎作用尚未被探索。我们假设TBI后静脉注射MAPCs可减弱炎症反应（通过小胶质细胞形态学测量），并改善运动任务和空间学习（Morris水迷宫[MWM]）的表现。在皮质挫伤损伤（CCI）后2和24小时静脉内施用MAPC。我们在TBI后120天测试了四组：假手术（未受伤），受伤但未治疗（CCI），以及受伤并用两种浓度的MAPC之一治疗，每公斤200万个细胞（CCI-2）或每公斤1000万个细胞（CCI-10）。CCI-10大鼠在平衡木上显示出左后肢缺陷的显著改善。在MWM试验的第五天，与CCI相比，CCI-10动物显示出到平台的潜伏期和行进距离的显著减少。探针试验显示，CCI-10中的接近度测量与CCI相比显着下降，表明记忆检索得到改善。通过计数同侧海马中活化的小胶质细胞来量化神经炎症。我们观察到CCI-10与CCI相比，齿状回中激活的小胶质细胞数量显著减少。我们的研究结果表明，在啮齿动物模型中TBI后静脉内MAPC治疗提供了空间学习的长期改善以及神经炎症的减弱。
We previously demonstrated that the intravenous delivery of multipotent adult progenitor cells (MAPCs) after traumatic brain injury (TBI) in rodents provides neuroprotection by preserving the blood-brain barrier and systemically attenuating inflammation in the acute time frame following cell treatment; however, the long-term behavioral and anti-inflammatory effects of MAPC administration after TBI have yet to be explored. We hypothesized that the intravenous injection of MAPCs after TBI attenuates the inflammatory response (as measured by microglial morphology) and improves performance at motor tasks and spatial learning (Morris water maze [MWM]). MAPCs were administered intravenously 2 and 24 hours after a cortical contusion injury (CCI). We tested four groups at 120 days after TBI: sham (uninjured), injured but not treated (CCI), and injured and treated with one of two concentrations of MAPCs, either 2 million cells per kilogram (CCI-2) or 10 million cells per kilogram (CCI-10). CCI-10 rats showed significant improvement in left hind limb deficit on the balance beam. On the fifth day of MWM trials, CCI-10 animals showed a significant decrease in both latency to platform and distance traveled compared with CCI. Probe trials revealed a significant decrease in proximity measure in CCI-10 compared with CCI, suggesting improved memory retrieval. Neuroinflammation was quantified by enumerating activated microglia in the ipsilateral hippocampus. We observed a significant decrease in the number of activated microglia in the dentate gyrus in CCI-10 compared with CCI. Our results demonstrate that intravenous MAPC treatment after TBI in a rodent model offers long-term improvements in spatial learning as well as attenuation of neuroinflammation.