BDNF, a neurotrophic factor, and its receptors have been implicated in the pathophysiology of mild traumatic brain injury (mTBI). The brainstem houses many vital functions, that are also associated with signs and symptoms of mTBI, but has been understudied in mTBI animal models. We determined the extent to which neurotrophic protein and associated receptor expression is affected within the brainstem of adult rats following mTBI. Their behavioral function was assessed and temporal expression of the ‘negative’ regulators of neuronal function (p75, t-TrkB, and pro-BDNF) and ‘positive’ neuroprotective (FL-TrkB and m-BDNF) protein isoforms were determined via western blot and immunohistochemistry at 1, 3, 7, and 14 post-injury days (PID) following mTBI or sham (control) procedure. Within the brainstem, p75 expression increased at PID 1 vs. sham animals. t-TrkB and pro-BDNF expression increased at PID 7 and 14. The ‘positive’ protein isoforms of FL-TrkB and m-BDNF expression were increased only at PID 7. The ratio of t-TrkB:FL-TrkB (negative:positive) was substantial across groups and time points, suggesting a negative impact of neurotrophic signaling on neuronal function. Additional NeuN experiments revealed cell death occurring within a subset of neurons within the medulla. While behavioral measures improved by PID 7–14, negative neurotrophic biochemical responses persisted. Despite the assertion that mTBI produces “mild” injury, evidence of cell death was observed in the medulla. Ratios of TrkB and BDNF isoforms with conflicting functions suggest that future work should specifically measure each subtype since they induce opposing downstream effects on neuronal function.

中文翻译：

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轻度创伤性脑损伤后脑干神经营养蛋白的时间表达

BDNF 是一种神经营养因子，其受体与轻度创伤性脑损伤 (mTBI) 的病理生理学有关。脑干拥有许多重要功能，这些功能也与 mTBI 的体征和症状相关，但在 mTBI 动物模型中尚未得到充分研究。我们确定了 mTBI 后成年大鼠脑干内神经营养蛋白和相关受体表达受到影响的程度。对他们的行为功能进行了评估，并通过蛋白质印迹测定了神经元功能“负”调节因子（p75、t-TrkB 和 pro-BDNF）和“正”神经保护蛋白亚型（FL-TrkB 和 m-BDNF）的时间表达mTBI 或假手术（对照）程序后，在受伤后 1、3、7 和 14 天 (PID) 进行免疫组织化学分析。在脑干内，与假手术动物相比，PID 1 时 p75 表达增加。 t-TrkB 和 pro-BDNF 表达在 PID 7 和 14 时增加。FL-TrkB 和 m-BDNF 表达的“阳​​性”蛋白亚型仅在 PID 7 时增加。t-TrkB:FL-TrkB 的比率（阴性：阳性）在各组和时间点上都很显着，表明神经营养信号对神经元功能有负面影响。其他 NeuN 实验揭示了髓质内一部分神经元内发生的细胞死亡。虽然 PID 7-14 时行为测量有所改善，但神经营养性生化负面反应仍然存在。尽管有人断言 mTBI 会产生“轻度”损伤，但在髓质中观察到细胞死亡的证据。具有冲突功能的 TrkB 和 BDNF 同工型的比率表明，未来的工作应该专门测量每种亚型，因为它们会对神经元功能产生相反的下游影响。