Animal models are critical for determining the mechanisms mediating traumatic brain injury-induced (TBI) neuropathology. Fluid percussion injury (FPI) is a widely used model of brain injury typically applied either midline or parasagittally (lateral). Midline FPI induces a diffuse TBI, while lateral FPI induces both focal cortical injury (ipsilateral hemisphere) and diffuse injury (contralateral hemisphere). Nonetheless, discrete differences in neuroinflammation and neuropathology between these two versions of FPI remain unclear. The purpose of this study was to compare acute (4–72 h) and subacute (7 days) neuroinflammatory responses between midline and lateral FPI. Midline FPI resulted in longer righting reflex times than lateral FPI. At acute time points, the inflammatory responses to the two different injuries were similar. For instance, there was evidence of monocytes and cytokine mRNA expression in the brain with both injuries acutely. Midline FPI had the highest proportion of brain monocytes and highest IL-1β/TNFα mRNA expression 24 h later. NanoString nCounter analysis 7 days post-injury revealed robust and prolonged expression of inflammatory-related genes in the cortex after midline FPI compared to lateral FPI; however, Iba-1 cortical immunoreactivity was increased with lateral FPI. Thus, midline and lateral FPI caused similar cortical neuroinflammatory responses acutely and mRNA expression of inflammatory genes was detectable in the brain 7 days later. The primary divergence was that inflammatory gene expression was greater and more diverse subacutely after midline FPI. These results provide novel insight to variations between midline and lateral FPI, which may recapitulate unique temporal pathogenesis.

动物模型对于确定介导创伤性脑损伤 (TBI) 神经病理学的机制至关重要。流体冲击损伤 (FPI) 是一种广泛使用的脑损伤模型，通常应用于中线或旁矢状（侧向）。中线 FPI 诱发弥漫性 TBI，而侧向 FPI 诱发局灶性皮质损伤（同侧半球）和弥漫性损伤（对侧半球）。尽管如此，这两种 FPI 版本之间神经炎症和神经病理学的离散差异仍不清楚。本研究的目的是比较中线和外侧 FPI 之间的急性（4-72 小时）和亚急性（7 天）神经炎症反应。中线 FPI 导致比横向 FPI 更长的翻正反射时间。在急性时间点，对两种不同损伤的炎症反应相似。例如，有证据表明大脑中的单核细胞和细胞因子 mRNA 都在急性损伤中表达。24 小时后，中线 FPI 的脑单核细胞比例最高，IL-1β/TNFα mRNA 表达最高。受伤后 7 天的 NanoString nCounter 分析显示，与侧向 FPI 相比，中线 FPI 后皮质中炎症相关基因的表达稳健且延长；然而，Iba-1 皮质免疫反应性随着侧向 FPI 增加。因此，中线和外侧 FPI 引起类似的皮质神经炎症反应，并且 7 天后在大脑中可检测到炎症基因的 mRNA 表达。主要的分歧是中线 FPI 后炎症基因表达更大和更多样化。这些结果为中线和横向 FPI 之间的变化提供了新的见解，