Therapeutic time window of multipotent adult progenitor therapy after traumatic brain injury

创伤性脑损伤后多能成体祖细胞治疗的治疗时间窗

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作者:Supinder S Bedi, Benjamin M Aertker, George P Liao, Henry W Caplan, Deepa Bhattarai, Fanni Mandy, Franciska Mandy, Luis G Fernandez, Pamela Zelnick, Matthew B Mitchell, Walter Schiffer, Margaret Johnson, Emma Denson, Karthik Prabhakara, Hasen Xue, Philippa Smith, Karen Uray, Scott D Olson, Robert W

Background

Traumatic brain injury (TBI) is a major cause of death and disability. TBI

Conclusions

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.

Methods

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.

Results

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. Conclusions: 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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