Dataset Information

Repurposing azithromycin for neonatal neuroprotection.

ABSTRACT:

Background

Inflammation contributes to neonatal hypoxic-ischemic brain injury pathogenesis. We evaluated the neuroprotective efficacy of azithromycin, a safe, widely available antibiotic with anti-inflammatory properties, in a neonatal rodent hypoxic-ischemic brain injury model.

Methods

Seven-day-old rats underwent right carotid artery ligation followed by 90-min 8% oxygen exposure; this procedure elicits quantifiable left forepaw functional impairment and right cerebral hemisphere damage. Sensorimotor function (vibrissae-stimulated forepaw placing, grip strength) and brain damage were compared in azithromycin- and saline-treated littermates 2-4 weeks later. Multiple treatment protocols were evaluated (variables included doses ranging from 15 to 45 mg/kg; treatment onset 15 min to 4 h post-hypoxia, and comparison of 1 vs. 3 injections).

Results

All azithromycin doses improved function and reduced brain damage; efficacy was dose dependent, and declined with increasing treatment delay. Three azithromycin injections, administered over 48 h, improved performance on both function measures and reduced brain damage more than a single dose.

Conclusion

In this neonatal rodent model, azithromycin improved functional and neuropathology outcomes. If supported by confirmatory studies in complementary neonatal brain injury models, azithromycin could be an attractive candidate drug for repurposing and evaluation for neonatal neuroprotection in clinical trials.

SUBMITTER: Barks JDE

PROVIDER: S-EPMC6764891 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Publications

Repurposing azithromycin for neonatal neuroprotection.

Barks John D E JDE Liu Yiqing Y Wang Lu L Pai Manjunath P MP Silverstein Faye S FS

Pediatric research 20190517 4

<h4>Background</h4>Inflammation contributes to neonatal hypoxic-ischemic brain injury pathogenesis. We evaluated the neuroprotective efficacy of azithromycin, a safe, widely available antibiotic with anti-inflammatory properties, in a neonatal rodent hypoxic-ischemic brain injury model.<h4>Methods</h4>Seven-day-old rats underwent right carotid artery ligation followed by 90-min 8% oxygen exposure; this procedure elicits quantifiable left forepaw functional impairment and right cerebral hemispher ...[more]

PMID: 31100754

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Dataset Information

Repurposing azithromycin for neonatal neuroprotection.

Background

Methods

Results

Conclusion

Publications

Repurposing azithromycin for neonatal neuroprotection.

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