Brabazon Fiona, Wilson Colin M, Jaiswal Shalini, Reed John, Frey William H, Byrnes Kimberly R
1 Neuroscience Program, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
2 Department of Radiology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
J Cereb Blood Flow Metab. 2017 Sep;37(9):3203-3218. doi: 10.1177/0271678X16685106. Epub 2017 Jan 6.
Traumatic brain injury (TBI) results in learning and memory dysfunction. Cognitive deficits result from cellular and metabolic dysfunction after injury, including decreased cerebral glucose uptake and inflammation. This study assessed the ability of intranasal insulin to increase cerebral glucose uptake after injury, reduce lesion volume, improve memory and learning function and reduce inflammation. Adult male rats received a controlled cortical impact (CCI) injury followed by intranasal insulin or saline treatment daily for 14 days. PET imaging of [18F]-FDG uptake was performed at baseline and at 48 h and 10 days post-injury and MRI on days three and nine post injury. Motor function was tested with the beam walking test. Memory function was assessed with Morris water maze. Intranasal insulin after CCI significantly improved several outcomes compared to saline. Insulin-treated animals performed better on beam walk and demonstrated significantly improved memory. A significant increase in [18F]-FDG uptake was observed in the hippocampus. Intranasal insulin also resulted in a significant decrease in hippocampus lesion volume and significantly less microglial immunolabeling in the hippocampus. These data show that intranasal insulin improves memory, increases cerebral glucose uptake and decreases neuroinflammation and hippocampal lesion volume, and may therefore be a viable therapy for TBI.
创伤性脑损伤（TBI）会导致学习和记忆功能障碍。认知缺陷是由损伤后的细胞和代谢功能障碍引起的，包括脑葡萄糖摄取减少和炎症反应。本研究评估了鼻内给予胰岛素对损伤后增加脑葡萄糖摄取、减少损伤体积、改善记忆和学习功能以及减轻炎症的能力。成年雄性大鼠接受控制性皮质撞击（CCI）损伤，随后每天给予鼻内胰岛素或生理盐水治疗，持续14天。在基线、损伤后48小时和10天进行[18F]-FDG摄取的PET成像，并在损伤后第3天和第9天进行MRI检查。用光束行走试验测试运动功能。用莫里斯水迷宫评估记忆功能。与生理盐水相比，CCI后鼻内给予胰岛素显著改善了多个结果。接受胰岛素治疗的动物在光束行走试验中表现更好，并且记忆力显著提高。在海马体中观察到[18F]-FDG摄取显著增加。鼻内胰岛素还导致海马体损伤体积显著减小，海马体中的小胶质细胞免疫标记显著减少。这些数据表明，鼻内胰岛素可改善记忆、增加脑葡萄糖摄取、减轻神经炎症和海马体损伤体积，因此可能是一种治疗TBI的可行疗法。
