Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China.
Neurocrit Care. 2024 Dec;41(3):925-941. doi: 10.1007/s12028-024-02018-x. Epub 2024 Jul 9.
Dynamic monitoring of the blood-brain barrier (BBB) functional status in septic mice can help to explore the pathological mechanisms. Therefore, we proposed a new method for monitoring BBB permeability and applied it to the detection of sepsis models.
The new method involves the construction of an optical cranial window and in vivo imaging. We performed dynamic monitoring of BBB permeability and cerebral blood flow (CBF) in cecal ligation puncture (CLP) and endotoxemia (lipopolysaccharide [LPS]) mice.
The sensitivity and accuracy of this method were higher than those of Evans blue evaluation. The increase of BBB permeability in the group of CLP mice was relatively mild and correlated with overall survival, and the damage was irreversible. Contrarily, BBB damage in the LPS group was more acute and severe, unrelated to overall survival, but recoverable. The CBF decreased significantly in both model mouse groups 24 h after modeling, but only the CBF proportion decrease in the LPS group was significantly correlated with an increase in BBB permeability. Within 24 h after both models were established, the decrease in blood flow in the digestive organs occurred earlier than in the brain and kidneys, and the decrease in small intestine blood flow in the LPS group progressed faster.
We have successfully demonstrated the feasibility of our novel method to detect BBB permeability in mice. Our results revealed a significant difference in the BBB permeability change trend between the CLP and LPS model mice when survival curves were consistent. Notably, the CLP-model mice demonstrated a closer resemblance to clinical patients. Our findings suggest that early-stage brain tissue hypoperfusion has a greater impact on BBB function damage in endotoxemia mice, which is related to the faster progression of blood flow redistribution.
动态监测脓毒症小鼠血脑屏障（BBB）功能状态有助于探索其病理机制。因此，我们提出了一种监测 BBB 通透性的新方法，并将其应用于脓毒症模型的检测。
该方法涉及光学颅窗的构建和体内成像。我们对盲肠结扎穿刺（CLP）和内毒素血症（脂多糖[LPS]）小鼠进行了 BBB 通透性和脑血流（CBF）的动态监测。
该方法的灵敏度和准确性均高于 Evans 蓝评估。CLP 小鼠 BBB 通透性的增加相对温和，与总生存率相关，且损伤不可逆。相反，LPS 组的 BBB 损伤更为急性和严重，与总生存率无关，但可恢复。建模后 24 小时，两组模型小鼠的 CBF 均明显下降，但仅 LPS 组 CBF 比例下降与 BBB 通透性增加显著相关。在两种模型建立后 24 小时内，肠道器官的血流量下降早于脑和肾脏，且 LPS 组的小肠血流量下降进展更快。
我们成功证明了我们的新方法检测小鼠 BBB 通透性的可行性。我们的结果表明，当生存曲线一致时，CLP 和 LPS 模型小鼠 BBB 通透性变化趋势存在显著差异。值得注意的是，CLP 模型小鼠与临床患者更为相似。我们的研究结果表明，早期脑组织低灌注对内毒素血症小鼠 BBB 功能损伤的影响更大，这与血流再分布的更快进展有关。
