Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, 69978, Israel.
Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Sci Rep. 2018 Sep 6;8(1):13340. doi: 10.1038/s41598-018-31623-y.
Traumatic Brain Injury (TBI) is one of the most common causes of neurological damage in young populations. It has been previously suggested that one of the mechanisms that underlie brain injury is Axonal Outgrowth Inhibition (AOI) that is caused by altered composition of the gangliosides on the axon surface. In the present study, we have found a significant reduction of GM1 ganglioside levels in the cortex in a closed head traumatic brain injury model of a mouse, induced by a weight drop device. In addition, axonal regeneration in the brains of the injured mice was affected as seen by the expression of the axonal marker pNF-H and the growth cones (visualized by F-actin and β-III-tubulin). NeuN immunostaining revealed mTBI-induced damage to neuronal survival. Finally, as expected, spatial and visual memories (measured by the Y-maze and the Novel Object Recognition tests, respectively) were also damaged 7 and 30 days post injury. A single low dose of GM1 shortly after the injury (2 mg/kg; IP) prevented all of the deficits mentioned above. These results reveal additional insights into the neuroprotective characteristics of GM1 in prevention of biochemical, cellular and cognitive changes caused by trauma, and may suggest a potential intervention for mTBI.
创伤性脑损伤 (TBI) 是年轻人中最常见的神经损伤原因之一。先前有人提出，轴突生长抑制 (AOI) 是导致脑损伤的机制之一，其原因是轴突表面神经节苷脂的组成发生了改变。在本研究中，我们发现一种通过重物坠落装置诱导的小鼠闭合性颅脑创伤模型中，皮质中的 GM1 神经节苷脂水平显著降低。此外，损伤小鼠大脑中的轴突再生受到影响，表现为轴突标志物 pNF-H 和生长锥的表达（通过 F-肌动蛋白和 β-III-微管蛋白可视化）。NeuN 免疫染色显示 mTBI 诱导的神经元存活损伤。最后，正如预期的那样，空间和视觉记忆（分别通过 Y 迷宫和新物体识别测试测量）在损伤后 7 天和 30 天也受到损害。损伤后立即给予单低剂量 GM1（2mg/kg；腹腔内注射）可预防上述所有缺陷。这些结果揭示了 GM1 在预防创伤引起的生化、细胞和认知变化方面的神经保护特性的更多见解，并可能为 mTBI 提供潜在的干预措施。
