■颅内出血(ICH),第二种最常见的中风亚型,加剧血脑屏障(BBB)的破坏,导致血管源性水肿,血浆蛋白外渗,和神经毒性物质的浸润。大脑的清除能力在维持BBB稳态和促进出血后患者恢复中起着至关重要的作用。本研究旨在探讨昼夜节律对BBB功能的影响,神经元损伤,和清除能力。
■将transwell模型和血红蛋白共培养,以模拟ICH后的BBB环境。不同光组干预后,确定神经元凋亡,分析了胶质细胞吞噬作用,免疫印迹法和免疫荧光双标法检测内源性清除相关蛋白水通道蛋白4(AQP4)和低密度脂蛋白受体相关蛋白1(LRP1)的表达,并定量分析了紧密连接蛋白occludin和褪黑素受体1A(MTNR1A)的表达。
■昼夜节律在维持血脑屏障的完整性方面起着关键作用,减少氧化应激诱导的神经元损伤,改善小胶质细胞吞噬作用。同时,与血红蛋白共培养的神经血管单元(NVU)中occludin和MTNR1A的表达提高了NVU内源性脑清除系统中关键蛋白AQP4和LRP1的表达。
■昼夜节律(黑白交替)保护ICH后的NVUBBB功能,促进血肿清除相关蛋白的表达,为ICH恢复期患者的临床治疗提供了新的证据,改善昼夜节律,促进脑代谢和血肿清除。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.