Probiotics relieve perioperative postoperative cognitive dysfunction induced by cardiopulmonary bypass through the kynurenine metabolic pathway.

ABSTRACT

Postoperative cognitive dysfunction (POCD) has become the popular critical post-operative consequences, especially cardiopulmonary bypass surgery, leading to an increased risk of mortality. However, no therapeutic effect about POCD. Probiotics are beneficial bacteria living in the gut and help to reduce the risk of POCD. However, the detailed mechanism is still not entirely known. Therefore, our research aims to uncover the effect and mechanism of probiotics in relieving POCD and to figure out the possible relationship between kynurenine metabolic pathway. 36 rats were grouped into three groups sham operated group (S group, n = 12), Cardiopulmonary bypass group (CPB group, n = 12), and probiotics+CPB (P group, n = 12). After CPB model preparation, water maze test and Garcia score scale was performed to identify the neurological function. Immunofluorescence and Hematoxylin and eosin staining has been used for hippocampal neurons detection. Brain injury related proteins, oxidative stress factors, and inflammatory factors were detected using enzyme-linked immunosorbent assays (ELISA). Neuronal apoptosis was detected by TdT-mediated dUTP nick end-labeling (TUNEL) staining and western blot. High-performance liquid chromatography/mass spectrometry (HPLC/MS) was performed to detect the key factors of the kynurenine metabolic pathway. Our results demonstrated that probiotics improved neurological function of post-CPB rats. The administration of probiotics ameliorated memory and learning in spatial terms CPB rats (P < 0.05). Hematoxylin and eosin (H&E) staining data, S-100ß and neuron-specific enolase (NSE) data convinced that probiotics agonists reduced brain damage in CPB rats (P < 0.05). Moreover, probiotics regulated inflammatory factors, meanwhile attenuated hippocampal neuronal apoptosis. Probiotics alleviated POCD in rats with CPB through regulation of kynurenine metabolic signaling pathway.