Objective: To evaluate the role of sphingosine-1-phosphate receptor 1 (S1PR1) in blood-brain barrier (BBB) injury after cardiac arrest-resuscitation in rats.
Methods: Sixty clean-grade healthy male Sprague-Dawley (SD) rats, aged 9-10 weeks, weight 300-320 g, were randomly divided into five groups using the random number table method: the sham group (group S), the cardiac arrest-resuscitation model group (group CAR), the S1PR1 agonist SEW2871 group (group SEW), the S1PR1 antagonist W146 group (group W), and the solvent DMSO group (group DMSO), 12 rats in each group. Group S underwent anesthesia, tracheal intubation, and femoral artery/venous catheterization only. Groups CAR, SEW, W, and DMSO were subjected to a transesophageal electrical stimulation-induced cardiac arrest-resuscitation model. Immediately after successful resuscitation, group SEW received an intraperitoneal injection of SEW2871 5 mg/kg, group W received an intraperitoneal injection of W146 1 mg/kg, and group DMSO received an equivalent volume of DMSO by intraperitoneal injection. Neurological deficit scores (NDS) were assessed 1 day after resuscitation. Rats were then euthanized for analysis, hippocampal S1PR1 and Caveolin-1 protein content were measured by Western blot, brain water content was determined by the wet-dry weight method, BBB permeability was evaluated via Evans blue (EB) extravasation and albumin content by using Western blot, and cerebrovascular endothelial cell vesicle density was observed and quantified by electron microscopy.
Results: Compared with group S, NDS and hippocampal S1PR1 protein contents were significantly reduced, Caveolin-1 contents, brain water content, EB permeability, albumin contents, and endothelial vesicle density were significantly increased in groups CAR, SEW, W, and DMSO (P < 0.05). Compared with group CAR, NDS and S1PR1 contents were significantly increased, Caveolin-1 contents, brain water content, EB permeability, albumin contents, and vesicle density were significantly reduced in group SEW (P < 0.05), NDS and hippocampal S1PR1 protein contents were significantly reduced, Caveolin-1 contents, brain water content, EB permeability, albumin contents, and endothelial vesicle density were significantly increased in group W (P < 0.05). Compared with group SEW, NDS and hippocampal S1PR1 protein contents were significantly reduced, Caveolin-1 contents, brain water content, EB permeability, albumin contents, and endothelial vesicle density were significantly increased in groups W and DMSO (P < 0.05).
Conclusion: S1PR1 plays a critical role in BBB injury following cardiac arrest-resuscitation in rats. Selective activation of S1PR1 alleviates post-resuscitation BBB damage and improves neurological function. |
