Esmolol Partially Ameliorates Blood-Brain Barrier Injury and Inhibits Glutamate Accumulation in Diffuse Axonal Injury Rats

Abstract

Background: To evaluate the therapeutic effects of esmolol on rats with diffuse axonal injury (DAI). Methods: DAI model rats were constructed by instantaneous high speed head rotation, and normal saline or esmolol hydrochloride was injected into the femoral vein after DAI induction. We scored the mNSS, observed the histology of brain tissues, evaluated blood-brain barrier (BBB) damage using Evans Blue (EB), and measured brain edema. We then detected the expressions of TNF-α, IL-6, IL-1β, MMP-9, cleaved-caspase-3, and cleaved-caspase-9 using western blots, quantified the contents of ROS, SOD, MDA, and CAT with related kits, measured the contents of Glu and Gln by HPLC, and calculated the Glu/Gln. Results: The DAI rat model was successfully constructed, and the optimal administration duration of esmolol was 3 d. Compared with the preoperative or Sham group, the mNSS, EB permeability, cerebral water content, the expressions of RECA-1, CD31, inflammatory proteins and apoptosis proteins, and the contents of ROS, MDA, Glu, and Gln were significantly increased, while the SOD and CAT contents were decreased (p < 0.05). However, administration of esmolol for 3 d partially reversed these trends and improved the histology of brain tissue. Conclusions: Esmolol partially ameliorated neurobehavioral abnormalities, BBB damage, and brain edema, inhibited inflammation, neuronal apoptosis and Glu accumulation, and repaired the ultrastructure of damaged neurons in DAI rats, thereby showing brain protection effects.