From the Departments of Pediatric Surgery (S.S.B., P.A.W., S.K.S., F.J., C.P.T., P.S., R.A.H., H.X., C.S.C.), Surgery (P.A.W., S.K.S., R.A.H., H.X., C.S.C.), and Neurobiology and Anatomy (P.K.D.), University of Texas, Health Science Center at Houston, Houston; and Michael E DeBakey Institute for Comparative Cardiovascular Science and Biomedical Devices (S.K.S.), Texas A & M University, College Station, Texas; and Blood Systems Research Institute (S.P.); and Department of Laboratory Medicine (S.P.), University of California San Francisco, San Francisco, California.
J Trauma Acute Care Surg. 2013 Sep;75(3):410-6. doi: 10.1097/TA.0b013e31829617c6.
Autologous bone marrow-derived mononuclear cells (AMNCs) have shown therapeutic promise for central nervous system insults such as stroke and traumatic brain injury (TBI). We hypothesized that intravenous injection of AMNC provides neuroprotection, which leads to cognitive improvement after TBI.
A controlled cortical impact (CCI) rodent TBI model was used to examine blood-brain barrier (BBB) permeability, neuronal and glial apoptosis, as well as cognitive behavior. Two groups of rats underwent CCI with AMNC treatment (CCI-autologous) or without AMNC treatment (CCI-alone), consisting of 2 million AMNC per kilogram body weight harvested from the tibia and intravenously injected 72 hours after injury. CCI-alone animals underwent sham harvests and received vehicle injections.
Ninety-six hours after injury, AMNC significantly reduced the BBB permeability in injured animals, and there was an increase in apoptosis of proinflammatory activated microglia in the ipsilateral hippocampus. At 4 weeks after injury, we observed significant improvement in probe testing of CCI-Autologous group in comparison to CCI-Alone in the Morris Water Maze paradigm.
Our data demonstrate that the intravenous injection of AMNC after TBI leads to neuroprotection by preserving early BBB integrity, increasing activated microglial apoptosis and improving cognitive function.
自体骨髓源性单核细胞（AMNCs）在治疗中枢神经系统损伤方面显示出了治疗潜力，如中风和创伤性脑损伤（TBI）。我们假设静脉注射 AMNC 可以提供神经保护，从而在 TBI 后改善认知功能。
使用控制性皮质撞击（CCI）啮齿动物 TBI 模型来检测血脑屏障（BBB）通透性、神经元和神经胶质细胞凋亡以及认知行为。两组大鼠接受 CCI 加 AMNC 治疗（CCI-自体）或不加 AMNC 治疗（CCI-单独），每公斤体重采集 200 万 AMNC，在损伤后 72 小时静脉注射。CCI-单独组动物进行假手术采集并接受载体注射。
损伤后 96 小时，AMNC 显著降低了损伤动物的 BBB 通透性，并增加了同侧海马体中促炎激活的小胶质细胞的凋亡。损伤后 4 周，我们观察到与 CCI-单独组相比，CCI-自体组在 Morris 水迷宫范式中的探针测试中表现出显著改善。
我们的数据表明，TBI 后静脉注射 AMNC 可通过保持早期 BBB 完整性、增加激活的小胶质细胞凋亡和改善认知功能来提供神经保护。
