Therapeutic time window of multipotent adult progenitor therapy after traumatic brain injury.
Therapeutic time window of multipotent adult progenitor therapy after traumatic brain injury.
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DOI：
10.1186/s12974-018-1122-8
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发表时间：
2018-03-16
影响因子：
9.3
通讯作者：
Cox CS Jr
中科院分区：
文献类型：
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作者：
Bedi SS;Aertker BM;Liao GP;Caplan HW;Bhattarai D;Mandy F;Mandy F;Fernandez LG;Zelnick P;Mitchell MB;Schiffer W;Johnson M;Denson E;Prabhakara K;Xue H;Smith P;Uray K;Olson SD;Mays RW;Cox CS Jr
创伤性脑损伤（TBI）是造成死亡和残疾的主要原因。创伤性脑损伤导致继发性中枢神经炎症反应延长。之前，我们已经证明，多剂量（TBI后2和24小时）静脉注射多能成人祖细胞（MAPC）可以保护血脑屏障（BBB），改善空间学习，减少海马齿状回中活化的小胶质细胞/巨噬细胞。为了确定是否存在保存血脑屏障、改善认知行为和减弱活化的小胶质细胞/巨噬细胞的最佳治疗窗口，我们在不同的临床相关时间间隔给药MAPC。我们分别在皮质挫伤（CCI）后2小时和24小时（2/24）、6小时和24小时（6/24）、12小时和36小时（12/36）、36小时和72小时（36/72）静脉注射MAPC，浓度为1000万/kg。在BBB实验中，分别于2/24、6/24和12/36接受MAPC治疗的动物在损伤后72 h安乐死。36/72处理组在伤后96 h采收。仅在TBI后2/24小时给药时，MAPC可导致血脑屏障通透性显著降低。在行为实验中，动物在行为范式后被采集。与皮质挫伤损伤（CCI）相比，在24小时或24小时前给药MAPC组的空间学习（损伤后120天）有显著改善。此外，仅与CCI相比，治疗组海马齿状回（2/24）中活化的小胶质细胞/巨噬细胞显著减少。CCI后24小时或之前静脉注射MAPC可改善血脑卒中，改善认知行为，减弱齿状回中活化的小胶质细胞/巨噬细胞。
Traumatic brain injury (TBI) is a major cause of death and disability. TBI results in a prolonged secondary central neuro-inflammatory response. Previously, we have demonstrated that multiple doses (2 and 24 h after TBI) of multipotent adult progenitor cells (MAPC) delivered intravenously preserve the blood-brain barrier (BBB), improve spatial learning, and decrease activated microglia/macrophages in the dentate gyrus of the hippocampus. In order to determine if there is an optimum treatment window to preserve the BBB, improve cognitive behavior, and attenuate the activated microglia/macrophages, we administered MAPC at various clinically relevant intervals. We administered two injections intravenously of MAPC treatment at hours 2 and 24 (2/24), 6 and 24 (6/24), 12 and 36 (12/36), or 36 and 72 (36/72) post cortical contusion injury (CCI) at a concentration of 10 million/kg. For BBB experiments, animals that received MAPC at 2/24, 6/24, and 12/36 were euthanized 72 h post injury. The 36/72 treated group was harvested at 96 h post injury. Administration of MAPC resulted in a significant decrease in BBB permeability when administered at 2/24 h after TBI only. For behavior experiments, animals were harvested post behavior paradigm. There was a significant improvement in spatial learning (120 days post injury) when compared to cortical contusion injury (CCI) in groups when MAPC was administered at or before 24 h. In addition, there was a significant decrease in activated microglia/macrophages in the dentate gyrus of hippocampus of the treated group (2/24) only when compared to CCI. Intravenous injections of MAPC at or before 24 h after CCI resulted in improvement of the BBB, improved cognitive behavior, and attenuated activated microglia/macrophages in the dentate gyrus.
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影响因子：
3.8
作者：
Harting, Matthew T.;Jimenez, Fernando;Adams, Sasha D.;Mercer, David W.;Cox, Charles S., Jr.
通讯作者：
Cox, Charles S., Jr.
影响因子：
6
作者：
Bedi, Supinder S.;Hetz, Robert;Cox, Charles S., Jr.
通讯作者：
Cox, Charles S., Jr.
DOI：
10.1097/ta.0b013e3181493080
发表时间：
2007-12-01
影响因子：
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作者：
Faul, Mark;Wald, Marlena M.;Sattin, Richard W.
通讯作者：
Sattin, Richard W.
影响因子：
4.8
作者：
Dalgard CL;Cole JT;Kean WS;Lucky JJ;Sukumar G;McMullen DC;Pollard HB;Watson WD
通讯作者：
Watson WD
DOI：
10.1038/jcbfm.2009.198
发表时间：
2010-01
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
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