Protective mechanisms of quercetin in neonatal rat brain injury induced by hypoxic-ischemic brain damage (HIBD).

Abstract

Neonatal hypoxic-ischemic brain damage (HIBD) is a leading cause of infant mortality worldwide. This study explored whether quercetin (Que) exerts neuroprotective effects in a rat model of HIBD. A total of 36 seven-day-old Sprague-Dawley rats were divided into control, Que, HI, and HI + Que groups. The Rice method was used to establish HIBD in HI and HI + Que rats, which were treated with hypoxia (oxygen concentration of 8%) for 2 h after ligation of the left common carotid artery. The rats in the HI + Que group were intraperitoneally injected with Que (30 mg/kg) 1 h before hypoxia, and the rats in the Que group were only injected with the same amount of Que. Brain tissues were harvested 24 h postoperation and assessed by hematoxylin and eosin staining, 2,3,5-triphenyltetrazolium chloride staining, and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay; relative gene and protein levels were evaluated by RT-qPCR, IHC, or western blot (WB) assay. Brain tissue morphologies were characterized by transmission electron microscopy (TEM); LC3B protein levels were assessed by immunofluorescence staining. Escape latencies and platform crossing times were significantly improved (p < .05) in HI + Que groups; infarct volume significantly decreased (p < .001), whereas the numbers of autophagic bodies and apoptotic cells increased and decreased, respectively. Meanwhile, NLRX1, ATG7, and Beclin1 expressions were significantly upregulated, and mTOR and TIM23 expressions, LC3B protein level, and LC 3II/LC 3I ratio were significantly downregulated. Que exerted neuroprotective effects in a rat model of HIBD by regulating NLRX1 and autophagy.