miR-34a overexpression protects against hippocampal neuron damage caused by ketamine-induced anesthesia in immature rats through the Notch-1/NF-κB signaling pathway

Am J Transl Res. 2021 Dec 15;13(12):13452-13461. eCollection 2021.

Abstract

Objective: To investigate the protective effect of miR-34a overexpression on hippocampal neuron damage caused by ketamine-induced anesthesia in immature rats and the underlying mechanism.

Methods: A total of 48 male SD rats were divided into control group (CG, n=12), ketamine group (KG, n=12), negative control group (NCG, n=12), and intervention group (IG, n=12) by using the random number table method. Neurological function, cognitive function, pathological changes of brain tissues, inflammatory cytokines, as well as mRNA expression levels of Notch-1, NICD, RBP-JK, and Hes-1 in brain tissues were detected in the four groups.

Results: The scores of auricular, paw withdrawal, corneal reflex, and escape reflexes of IG were higher than those of KG and NCG (P<0.05). At day 3 after intervention, the escape latency, time of staying in the quadrants of original platform, and times of crossing the quadrants of original platform of IG were lower than those of KG and NCG (P<0.05). HE staining results revealed that the morphology and structure of a few neurons and glial cells in IG were changed, and the intercellular space was increased. The brain tissues of NCG demonstrated marked neuron damage with unclear structure; these changes were less significant for KG. The levels of TNF-α, IL-1β, and IL-6 of IG were lower than those of KG and CG (P<0.05).

Conclusions: miR-34a overexpression exhibited a potent protective effect on hippocampal neuron damage caused by ketamine-induced anesthesia in immature rats.

Keywords: Notch-1/NF-κB signaling pathway; hippocampal neuron; ketamine-induced anesthesia; miR-34a overexpression; protective effect.