Department of Neurosurgery, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin, 300052, China.
Tianjin Neurological Institute, Key Laboratory of Post Neuro-Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, China.
Acta Neuropathol Commun. 2023 Apr 7;11(1):61. doi: 10.1186/s40478-023-01555-4.
The persistent dysregulation and accumulation of poisonous proteins from destructive neural tissues and cells activate pathological mechanisms after traumatic brain injury (TBI). The lymphatic drainage system of the brain, composed of the glymphatic system and meningeal lymphatic vessels (MLVs), plays an essential role in the clearance of toxic waste after brain injury. The neuroprotective effect of interleukin 33 (IL-33) in TBI mice has been demonstrated; however, its impact on brain lymphatic drainage is unclear. Here, we established a fluid percussion injury model to examine the IL-33 administration effects on neurological function and lymphatic drainage in the acute brain of TBI mice. We verified that exogenous IL-33 could improve the motor and memory skills of TBI mice and demonstrated that in the acute phase, it increased the exchange of cerebrospinal and interstitial fluid, reversed the dysregulation and depolarization of aquaporin-4 in the cortex and hippocampus, improved the drainage of MLVs to deep cervical lymph nodes, and reduced tau accumulation and glial activation. We speculate that the protective effect of exogenous IL-33 on TBI mice's motor and cognitive functions is related to the enhancement of brain lymphatic drainage and toxic metabolite clearance from the cortex and hippocampus in the acute stage. These data further support the notion that IL-33 therapy may be an effective treatment strategy for alleviating acute brain injury after TBI.
破坏性的神经组织和细胞产生的有毒蛋白质持续失调和积累，会在创伤性脑损伤 (TBI) 后激活病理机制。脑的淋巴引流系统由神经胶质淋巴系统和脑膜淋巴管 (MLVs) 组成，在脑损伤后清除毒性废物方面发挥着重要作用。白细胞介素 33 (IL-33) 在 TBI 小鼠中的神经保护作用已得到证实；然而，其对脑淋巴引流的影响尚不清楚。在这里，我们建立了一个流体冲击损伤模型，以研究 IL-33 给药对 TBI 小鼠急性脑淋巴引流和神经功能的影响。我们验证了外源性 IL-33 可以改善 TBI 小鼠的运动和记忆能力，并表明在急性期，它增加了脑脊液和细胞间隙液的交换，逆转了皮质和海马中水通道蛋白 4 的失调和去极化，改善了 MLVs 向深部颈淋巴结的引流，并减少了 tau 积累和神经胶质激活。我们推测，外源性 IL-33 对 TBI 小鼠运动和认知功能的保护作用与增强脑淋巴引流和从皮质和海马中清除有毒代谢物有关，这在急性期尤为明显。这些数据进一步支持了这样一种观点，即 IL-33 疗法可能是缓解 TBI 后急性脑损伤的有效治疗策略。
