Apolipoprotein E (apoE) plays a role in various physiological functions including lipid transport, synaptic plasticity, and immune modulation. Epidemiological studies suggest that the apoE4 allele increases the risk of post-traumatic sequelae. This study was performed to investigate regionspecific effects of the apoE4 isoform on post-traumatic neurodegeneration. Two focal brain injuries were introduced separately in the motor cortex and hippocampus of apoE4 knock-in, apoE3 knock-in, apoE knockout, and wild-type (WT) mice. Western blotting showed that the expression levels of pre-synaptic and post-synaptic markers at the recovery stage were lower in the hippocampal injury core in apoE4 mice, compared with apoE3 and WT mice. Fast glial activation (determined by immunohistochemistry with glial fibrillary acidic protein, ionized calcium binding adaptor molecule 1, and cluster of differentiation 45 antibodies) was characteristic of apoE4 mice with hippocampal injury penumbra. apoE4-specific changes were not observed after cortical injury. The intensity of microglial activation in the hippocampus was inversely correlated with the volume of injury reduction on sequential magnetic resonance imaging examinations, when validated using matched samples. These findings indicate that the effects of the interaction between apoE4 and focal brain damage are specific to the hippocampus. Manipulation of inflammatory cell responses could be beneficial for reducing post-traumatic hippocampal neurodegeneration in apoE4 carriers.

中文翻译：

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Apoe4 依赖性对局灶性脑损伤反应的区域特异性差异。

载脂蛋白 E (apoE) 在各种生理功能中发挥作用，包括脂质转运、突触可塑性和免疫调节。流行病学研究表明，apoE4 等位基因会增加创伤后后遗症的风险。进行这项研究是为了研究 apoE4 同种型对创伤后神经变性的区域特异性影响。在 apoE4 敲入、apoE3 敲入、apoE 敲除和野生型 (WT) 小鼠的运动皮层和海马中分别引入了两种局灶性脑损伤。Western印迹显示，与apoE3和WT小鼠相比，apoE4小鼠海马损伤核心恢复期突触前和突触后标志物的表达水平较低。快速神经胶质激活（通过免疫组织化学与神经胶质纤维酸性蛋白、离子钙结合接头分子 1 和分化簇 45 抗体）是具有海马损伤半暗带的 apoE4 小鼠的特征。皮质损伤后未观察到 apoE4 特异性变化。当使用匹配样本进行验证时，海马中小胶质细胞激活的强度与连续磁共振成像检查的损伤减少量呈负相关。这些发现表明 apoE4 与局灶性脑损伤之间相互作用的影响是特定于海马的。操纵炎症细胞反应可能有利于减少 apoE4 携带者的创伤后海马神经变性。皮质损伤后未观察到 apoE4 特异性变化。当使用匹配样本进行验证时，海马中小胶质细胞激活的强度与连续磁共振成像检查的损伤减少量呈负相关。这些发现表明 apoE4 与局灶性脑损伤之间相互作用的影响是特定于海马的。操纵炎症细胞反应可能有利于减少 apoE4 携带者的创伤后海马神经变性。皮质损伤后未观察到 apoE4 特异性变化。当使用匹配样本进行验证时，海马中小胶质细胞激活的强度与连续磁共振成像检查的损伤减少量呈负相关。这些发现表明 apoE4 与局灶性脑损伤之间相互作用的影响是特定于海马的。操纵炎症细胞反应可能有利于减少 apoE4 携带者的创伤后海马神经变性。这些发现表明 apoE4 与局灶性脑损伤之间相互作用的影响是特定于海马的。操纵炎症细胞反应可能有利于减少 apoE4 携带者的创伤后海马神经变性。这些发现表明 apoE4 与局灶性脑损伤之间相互作用的影响是特定于海马的。操纵炎症细胞反应可能有利于减少 apoE4 携带者的创伤后海马神经变性。