Objective Intracranial hemorrhage (ICH), the second most common subtype of stroke, exacerbates the disruption of the blood-brain barrier (BBB), leading to vasogenic edema, plasma protein extravasation, and infiltration of neurotoxic substances. The clearance capacity of the brain plays a crucial role in maintaining BBB homeostasis and facilitating patient recovery after hemorrhage. This study aimed to investigate the effect of circadian rhythms on BBB function, neuronal damage, and clearance capabilities. Methods The transwell model and hemoglobin were co-cultured to simulate the BBB environment after ICH. After intervention with different light groups, neuronal apoptosis was determined, glial phagocytosis was analyzed, the expression of endogenous clearing-related proteins aquaporin 4 (AQP4) and low-density lipoprotein receptor-related protein 1 (LRP1) was detected by western blotting and immunofluorescence dual standard method, and the expression of the tight junction protein occludin and melatonin receptor 1A (MTNR1A) was quantitatively analyzed. Results Circadian rhythms play a key role in maintaining the integrity of the BBB, reducing oxidative stress-induced neuronal damage, and improving microglial phagocytosis. Meanwhile, the expression of occludin and MTNR1A in neurovascular unit (NVU) co-cultured with hemoglobin improved the expression of AQP4 and LRP1, the key proteins in the NVU's endogenous brain clearance system. Conclusion Circadian rhythm (alternating black and white light) protects the NVU BBB function after ICH, promotes the expression of proteins related to the clearance of the hematoma, provides new evidence for the clinical treatment of patients recovering from ICH, and improves the circadian rhythm to promote brain metabolism and hematoma clearance.
基金:
National Natural Science Foundation of China [82160237]; Key Research and Development Program in Hainan Province [ZDYF2023SHFZ104]; Natural Science Foundation of Hainan Province [822MS210]
第一作者机构:[1]Shanxi Med Univ, Clin Sch Med 2, Dept Neurol, Taiyuan 030002, Shanxi, Peoples R China
通讯作者:
通讯机构:[2]Shanxi Med Univ, Clin Sch Med 2, Taiyuan 030002, Shanxi, Peoples R China[4]Hainan Med Univ, Sanya Cent Hosp, Hainan Peoples Hosp 3, Dept Neurol, Sanya 57200, Hainan, Peoples R China
推荐引用方式(GB/T 7714):
Xue Fang,Chen Wenchao,Lian Xia,et al.The Regulatory Role and Mechanism of Circadian Rhythm in Hemoglobin Co-cultured Neurovascular Unit[J].BIOMEDICAL AND ENVIRONMENTAL SCIENCES.2024,37(7):726-738.doi:10.3967/bes2024.090.
APA:
Xue, Fang,Chen, Wenchao,Lian, Xia,He, Guanghui,Tian, Jingyuan...&Wang, Gaiqing.(2024).The Regulatory Role and Mechanism of Circadian Rhythm in Hemoglobin Co-cultured Neurovascular Unit.BIOMEDICAL AND ENVIRONMENTAL SCIENCES,37,(7)
MLA:
Xue, Fang,et al."The Regulatory Role and Mechanism of Circadian Rhythm in Hemoglobin Co-cultured Neurovascular Unit".BIOMEDICAL AND ENVIRONMENTAL SCIENCES 37..7(2024):726-738