Azithromycin reduces inflammation-amplified hypoxic-ischemic brain injury in neonatal rats.

Abstract

Background:Systemic inflammation amplifies neonatal hypoxic-ischemic (HI) brain injury. Azithromycin (AZ), an antibiotic with anti-inflammatory properties, improves sensorimotor function and reduces tissue damage after neonatal rat HI brain injury.Objective:To determine if AZ is neuroprotective in two neonatal rat models of inflammation-amplified HI brain injury.Design/Methods:Seven-day-old (P7) rats received injections of toll-like receptor agonists lipopolysaccharide (LPS) or Pam3Cys-Ser-(Lys)4 (PAM) prior to right carotid ligation followed by 50 min (LPS+HI) or 60 min (PAM+HI) in 8% oxygen. Outcomes included contralateral forelimb function (forepaw placing; grip strength), survival, %intact right hemisphere (brain damage), and a Composite Score incorporating these measures. We compared P35 outcomes in controls and groups treated with 3 or 5 AZ doses. Then, we compared P21 outcomes when the first (of 5) AZ doses was administered 1, 2, or 4 hours after HI.Results:In both LPS+HI and PAM+HI models, AZ improved sensorimotor function, survival, brain tissue preservation, and Composite Scores. Benefits increased with 5 vs. 3-dose AZ and declined with longer initiation delay.Conclusion:Perinatal systemic infection is a common comorbidity of neonatal asphyxia brain injury and contributes to adverse outcomes. These data support further evaluation of AZ as a candidate treatment for neonatal neuroprotection.