The lectin pathway (LP) of complement activation is believed to contribute to brain inflammation. The study aims to identify the key components of the LP contributing to TBI outcome as possible novel pharmacological targets. We compared the long-term neurological deficits and neuropathology of wild-type mice (WT) to that of mice carrying gene deletions of key LP components after experimental TBI. WT or MASP-2 (Masp2−/−), ficolin-A (Fcna−/−), CL-11 (Colec11−/−), MASP-1/3 (Masp1−/−), MBL-C (Mbl2−/−), MBL-A (Mbl1−/−) or MBL−/− (Mbl1−/−/Mbl2−/−) deficient male C57BL/6J mice were used. Mice underwent sham surgery or TBI by controlled cortical impact. The sensorimotor response was evaluated by neuroscore and beam walk tests weekly for 4 weeks. To obtain a comparative analysis of the functional outcome each transgenic line was rated according to a health score calculated on sensorimotor performance. For selected genotypes, brains were harvested 6 weeks after injury for histopathological analysis. MASP-2−/−, MBL−/− and FCN-A−/− mice had better outcome scores compared to WT. Of these, MASP-2−/− mice had the best recovery after TBI, showing reduced sensorimotor deficits (by 33% at 3 weeks and by 36% at 4 weeks). They also showed higher neuronal density in the lesioned cortex with a 31.5% increase compared to WT. Measurement of LP functional activity in plasma from MASP-2−/− mice revealed the absence of LP functional activity using a C4b deposition assay. The LP critically contributes to the post-traumatic inflammatory pathology following TBI with the highest degree of protection achieved through the absence of the LP key enzyme MASP-2, underlining a therapeutic utility of MASP-2 targeting in TBI.

中文翻译：

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补体凝集素途径基因的靶向缺失可改善创伤性脑损伤的结果，MASP-2 起主要作用

补体激活的凝集素途径 (LP) 被认为有助于脑部炎症。该研究旨在将有助于 TBI 结果的 LP 的关键成分确定为可能的新药理学靶点。我们将野生型小鼠 (WT) 的长期神经功能缺损和神经病理学与实验性 TBI 后携带关键 LP 成分基因缺失的小鼠进行了比较。WT 或 MASP-2 (Masp2-/-)、ficolin-A (Fcna-/-)、CL-11 (Colec11-/-)、MASP-1/3 (Masp1-/-)、MBL-C (Mbl2- /-)、MBL-A (Mbl1-/-) 或 MBL-/- (Mbl1-/-/Mbl2-/-) 缺乏雄性 C57BL/6J 小鼠。小鼠通过受控的皮质冲击接受了假手术或 TBI。每周通过神经评分和光束步行测试评估感觉运动反应，持续 4 周。为了获得功能结果的比较分析，根据根据感觉运动性能计算的健康评分对每个转基因品系进行评级。对于选定的基因型，在损伤后 6 周收获大​​脑用于组织病理学分析。与 WT 相比，MASP-2-/-、MBL-/- 和 FCN-A-/- 小鼠的结果得分更好。其中，MASP-2-/- 小鼠在 TBI 后恢复最好，感觉运动障碍减少（3 周时减少 33%，4 周时减少 36%）。与 WT 相比，它们还在受损皮层中显示出更高的神经元密度，增加了 31.5%。MASP-2-/- 小鼠血浆中 LP 功能活性的测量显示使用 C4b 沉积测定不存在 LP 功能活性。