Objective To investigate the effects of different usage frequencies and total doses of mannitol on cerebral arterial blood flow, serum S100β protein concentration, and the protein and mRNA expression of the TLR4 and NF-κB in brain tissue after cardiopulmonary resuscitation ( CPR) in rats,and to explore the role of mannitol in brain injury after CPR. Methods A total of 120 male Wistar rats were used to establish a cardiac arrest and CPR model, and were randomly divided into 3 groups ( n = 40, sham operation group, model group, and mannitol intervention group) . The model group and mannitol intervention group underwent the same model. After successful resuscitation, the mannitol intervention group received 20% mannitol at different time points.The sham operation group only underwent intubation through the trachea and catheter placement via femoral artery and vein puncture. Laser Doppler flowmeter was used to monitor the changes in cerebral arterial blood flow in the rats at 6, 12,18, and 24 h after surgery. Tissue specimens were collected from the rats at 6, 12, 18, and 24 h after surgery for detection of serum S100β protein concentration using ELISA method. H&E staining was used to observe the pathological changes in rat brain tissue, and Western blot was used to detect the protein expression levels of TLR4 and NF-κB. Real-time PCR was used to detect the mRNA expression levels of TLR4 and NF-κB. Results The cerebral arterial blood flow in the model group was significantly lower than that in the sham operation group after the restoration of spontaneous circulation, and the difference was statistically significant ( P < 0. 05) . In the mannitol intervention group, the cerebral arterial blood flow in rats increased after mannitol administration 5 times during the 6, 12, and 18 h post-surgery periods, and decreased after 7 times of mannitol administration ( 24 h) , with no significant difference compared to the model group.Swelling of hippocampal neurons, increased nuclear staining and shrinking, increased glial cell proliferation, and disordered arrangement of neurons were observed in the model group. In the mannitol intervention group, the arrangement of neurons in the cerebral cortex and hippocampal tissue was more orderly than that in the model group at 12 h post-surgery, with reduced cell necrosis. A large number of deep-stained and shriveled neuronal nuclei were observed at 24 h post surgery. A significant increase in the S100β protein content in rat serum was observed in both the model group and the mannitol intervention group at 12 h post-surgery, compared to the sham operation group.The S100β protein content in the model group significantly increased at 6, 12, 18, and 24 h post-surgery (P<0. 05) , while in the mannitol intervention group, the S100β protein content significantly decreased at 6, 12, and 18 h post-surgery (P<0. 05) compared to the model group, with no significant difference at 24 h post-surgery. Compared to the sham operation group, the protein and mRNA expression levels of TLR4 and NF-κB in hippocampal tissue of rats in the model group significantly increased at 6, 12, 18, and 24 h post-surgery (P<0. 05) . However, in the mannitol intervention group, the protein and mRNA expression levels of TLR4 and NF-κB in the hippocampal tissue significantly decreased at 6, 12, and 18 h post-surgery (P<0. 05) , and the protein and mRNA expression levels of TLR4 in the hippocampal tissue were significantly decreased at 24 h post-surgery ( P< 0. 05) . Conclusion Moderate amounts of mannitol can improve cerebral arterial blood flow, reduce serum S100β protein, and decrease the protein and mRNA expression levels of TLR4 and NF-κB in brain tissue after CPR, thereby protecting brain tissue and alleviating secondary brain injury. Excessive mannitol may cause cerebral edema, worsen intracranial hypertension, and lead to more severe secondary brain injury.

cardiopulmonary resuscitation, brain edema, mannitol, cerebral arterial blood flow, S100 protein, TLR4 / NF-κB pathway

心肺复苏, 脑水肿, 甘露醇, 大脑动脉血流, S100 蛋白, TLR4 / NF-κB 通路