2. Academic Validation
  3. Improving the function of meningeal lymphatic vessels to promote brain edema absorption after TBI

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

  • J Neurotrauma. 2022 Sep 15. doi: 10.1089/neu.2022.0150.
Jianwen Liao 1 2,  Mingchao Zhang 3 4,  Zichuan Shi 5,  Hao Lu 6,  Lichen Wang 7,  Weijia Fan 8,  Xiaoguang Tong 9 10,  Hua Yan 11 12
Affiliations

Affiliations

  • 1 Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, Tianjin, Tianjin, China.
  • 2 Tianjin Medical University, Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin, Tianjin, China; liaojianwen0826@163.com.
  • 3 Tianjin Medical University, Clinical College of Neurology, Neurosurgery and Neurorehabilitation，, Tianjin, Tianjin, China.
  • 4 Tianjin Huanhu Hospital, Tianjin, Tianjin, China; zhangmingchao2009@163.com.
  • 5 Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Department of Neurology, Tianjin, China; tjszc1018@163.com.
  • 6 Tianjin Huanhu Hospital, Tianjin, Tianjin, China; luhao@tmu.edu.cn.
  • 7 Tianjin Huanhu Hospital, Tianjin, Tianjin, China; WLChen0404@163.com.
  • 8 Tianjin Huanhu Hospital, Tianjin, Tianjin, China; justonly000@163.com.
  • 9 Tianjin Huanhu Hospital, Tianjin, Tianjin, China.
  • 10 Tianjin Medical University, Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin, Tianjin, China; tongxg@yahoo.com.
  • 11 Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, Tianjin, China.
  • 12 Tianjin Medical University, Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin, Tianjin, China; yanhua20042007@sina.com.
PMID: 36106596 DOI: 10.1089/neu.2022.0150
Abstract

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.

Keywords

ANIMAL STUDIES; Brain Edema; Medication; TRAUMATIC BRAIN INJURY.

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