Azithromycin reduces inflammation-amplified hypoxic-ischemic brain injury in neonatal rats
| Autor: | John D.E. Barks, Yiqing Liu, Faye S. Silverstein, Ian A Dopp |
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| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
Lipopolysaccharide Anti-Inflammatory Agents Inflammation Brain damage Pharmacology Azithromycin Systemic inflammation Neuroprotection chemistry.chemical_compound medicine Animals Rats Wistar Receptor Asphyxia business.industry Toll-Like Receptors Brain Anti-Bacterial Agents Rats Oxygen Neuroprotective Agents chemistry Animals Newborn Brain Injuries Pediatrics Perinatology and Child Health Hypoxia-Ischemia Brain medicine.symptom business medicine.drug |
| Zdroj: | Pediatric research. 92(2) |
| ISSN: | 1530-0447 |
| Popis: | 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. The objective of this study was 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 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. Results In 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. Conclusions 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. Impact AZ 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. |
| Databáze: | OpenAIRE |
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