Improving the function of meningeal lymphatic vessels to promote brain edema absorption after TBI

Brain edema is the most common and fatal complication after traumatic brain injury. Meningeal lymphatic vessels (MLVs) are the conduits that transport cerebrospinal fluid (CSF) and macromolecules to deep extracranial cervical lymph nodes (dCLNs). After TBI, the drainage function of MLVs can become impaired. However, the scenario as to whether the improvement of the function of MLVs can promote brain edema absorption after TBI has not been reported. Thus, the purpose of this study was to investigate the effects of Ketoprofen, 9-cisRA and VEGF-C (which promote the proliferation of peripheral lymphatic vessels) on the cerebellar medullary cistern injection of TBI rats, as well as their mechanism of action on brain edema after TBI. In the experiment, we found that Ketoprofen, 9-cisRA and VEGF-C can improve the function of MLVs, promote the extracranial drainage of CSF and the absorption of brain edema, weaken the neuroinflammatory response, reduce ROS production, maintain the structural integrity of MLVs and improve neurological function. In addition, Ketoprofen, 9-cisRA and VEGF-C upregulated the lymphatic-specific proteins VEGFR3/Flt-4, PROX1, FOXC2 and LYVE1. These results indicate that Ketoprofen, 9-cisRA and VEGF-C may maintain the integrity of the meningeal lymphatic wall and promote lymphatic proliferation by upregulating the expression of lymphatic vessel-specific proteins, improve meningeal lymphatic function after TBI, promote CSF drainage and brain edema absorption, reduce the immune response of the nervous system and reduce ROS formation, thereby improving prognoses. These findings may provide new ideas for the treatment of brain edema after TBI.