Evidence map›Paper›PMID 42243503›Full record

ArticlePediatric research2026

Comparing neuroprotective drug efficacy in rodent neonatal brain injury models.

John D E Barks, Yiqing Liu, Julie Sturza, Niko Kaciroti, William J Meurer, Faye S Silverstein

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Article in Pediatric research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

John D E BarksDepartment of Pediatrics, University of Michigan Medical School, The University of Michigan, Ann Arbor, MI, USA. jbarks@med.umich.edu.
Yiqing LiuDepartment of Pediatrics, University of Michigan Medical School, The University of Michigan, Ann Arbor, MI, USA.
Julie SturzaDepartment of Pediatrics, University of Michigan Medical School, The University of Michigan, Ann Arbor, MI, USA.
Niko KacirotiDepartment of Pediatrics, University of Michigan Medical School, The University of Michigan, Ann Arbor, MI, USA.
William J MeurerDepartment of Neurology, University of Michigan Medical School, The University of Michigan, Ann Arbor, MI, USA.
Faye S SilversteinDepartment of Pediatrics, University of Michigan Medical School, The University of Michigan, Ann Arbor, MI, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundA challenge in preclinical neonatal neuroprotection research is the implementation of study designs that enable direct comparison of multiple potentially effective drugs. We used adaptive design to test four FDA-approved drugs (azithromycin, erythropoietin, caffeine, and melatonin) concurrently and determine which best combined safety and efficacy.

methodsSeven-day-old (P7) rats underwent hypoxia-ischemia (HI; right carotid ligation + timed 8% O

resultsIn all models, either azithromycin or erythropoietin (EPO) offered superior neuroprotection at P21, and the other was "runner-up". Caffeine and melatonin conferred modest neuroprotection in pure HI but were quickly eliminated in hypothermia-treated HI. At P35, azithromycin and EPO outcomes were generally similar.

conclusionThese results support azithromycin as a candidate neuroprotective agent that warrants future studies in large animal neonatal cerebral hypoxia-ischemia models. IMPACT: We used adaptive design to compare four repurposed drugs (azithromycin, caffeine, erythropoietin, and melatonin) in neonatal rodent brain injury. Key factors differentiating our approach from existing reports were within-litter comparisons, evaluation in multiple models, and measurement of both function and neuropathology. Either azithromycin or erythropoietin was the most neuroprotective in any given model, with the other a close "runner-up". Melatonin and caffeine were neuroprotective in pure HI, but less effective than azithromycin. In other models, they were less effective and eliminated early by the Bayesian algorithm. This supports azithromycin as a candidate neuroprotectant and supports future studies in large animal models.

Identifiers

PMID42243503

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