Related Experiment Video
Updated: Jan 16, 2026
Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury
Published on: November 24, 2017
Comparing Neuroprotective Drug Efficacy in Rodent Neonatal Brain Injury Models
John D E Barks1, Yiqing Liu1, Julie Sturza1
1Department of Pediatrics, University of Michigan Medical School, The University of Michigan, Ann Arbor, MI.
Background:
A challenge in preclinical neonatal neuroprotection research is 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, melatonin) concurrently and determine which best combined safety and efficacy.
Methods:
Seven-day-old (P7) rats underwent hypoxia-ischemia (HI; right carotid ligation + timed 8% O2 exposure); some experiments included pre-treatment with agents that induced inflammation, and some included post-HI brief moderate hypothermia. Sensorimotor and neuropathology measures were incorporated into a Composite Score that also accounted for deaths. Outcome was initially evaluated at P21 and in confirmatory studies at P35. A pre-specified Bayesian algorithm with futility and efficacy stopping rules was devised to analyze emerging data and adjust subsequent animal allocation among drug groups.
Results:
In 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.
Conclusion:
These results support azithromycin or erythropoietin as candidate neuroprotective agents and warrant future studies in large animal neonatal cerebral hypoxia-ischemia models.
