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Azithromycin reduces inflammation-amplified hypoxic–ischemic brain injury in neonatal rats
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Azithromycin reduces inflammation-amplified hypoxic–ischemic brain injury in neonatal rats
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Azithromycin reduces inflammation-amplified hypoxic–ischemic brain injury in neonatal rats
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Journal Article
Azithromycin reduces inflammation-amplified hypoxic–ischemic brain injury in neonatal rats
2022
Overview
BackgroundSystemic 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. The objective of this study was to determine if AZ is neuroprotective in two neonatal rat models of inflammation-amplified HI brain injury.Design/MethodsSeven-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 postnatal day 35 outcomes in controls and groups treated with three or five AZ doses. Then, we compared P21 outcomes when the first (of five) AZ doses were administered 1, 2, or 4 h after HI.ResultsIn both LPS + HI and PAM + HI models, AZ improved sensorimotor function, survival, brain tissue preservation, and composite scores. Benefits increased with five- vs. three-dose AZ and declined with longer initiation delay.ConclusionsPerinatal 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.ImpactAZ treatment decreases sensorimotor impairment and severity of brain injury, and improves survival, after inflammation-amplified HI brain injury, and this can be achieved even with a 2 h delay in initiation.This neuroprotective benefit is seen in models of inflammation priming by both Gram-negative and Gram-positive infections.This extends our previous findings that AZ treatment is neuroprotective after HI brain injury in neonatal rats.
Publisher
Nature Publishing Group
Subject
