Infantile Cocktail of Erythropoietin and Melatonin Restores Gait in Adult Rats with Preterm Brain Injury

Lauren L. Jantzie, Sankar Muthukumar, Yuma Kitase, Vikram Vasan, Mohammed A. Fouda, Sarah Hamimi, Christopher Burkhardt, Vera Joanna Burton, Gwendolyn Gerner, Joseph Scafidi, Xiaobu Ye, Frances J. Northington, Shenandoah Robinson

Research output: Contribution to journalArticlepeer-review


Cerebral palsy (CP) is the most common cause of physical disability for children worldwide. Many infants and toddlers are not diagnosed with CP until they fail to achieve obvious motor milestones. Currently, there are no effective pharmacologic interventions available for infants and toddlers to substantially improve their trajectory of neurodevelopment. Because children with CP from preterm birth also exhibit a sustained immune system hyper-reactivity, we hypothesized that neuro-immunomodulation with a regimen of repurposed endogenous neurorestorative medications, erythropoietin (EPO) and melatonin (MLT), could improve this trajectory. Thus, we administered EPO + MLT to rats with CP during human infant-toddler equivalency to determine whether we could influence gait patterns in mature animals. After a prenatal injury on embryonic day 18 (E18) that mimics chorioamnionitis at ∼25 weeks human gestation, rat pups were born and raised with their dam. Beginning on postnatal day 15 (P15), equivalent to human infant ∼1 year, rats were randomized to receive either a regimen of EPO + MLT or vehicle (sterile saline) through P20. Gait was assessed in young adult rats at P30 using computerized digital gait analyses including videography on a treadmill. Results indicate that gait metrics of young adult rats treated with an infantile cocktail of EPO + MLT were restored compared to vehicle-treated rats (p < 0.05) and similar to sham controls. These results provide reassuring evidence that pharmacological interventions may be beneficial to infants and toddlers who are diagnosed with CP well after the traditional neonatal window of intervention.

Original languageEnglish (US)
Pages (from-to)266-276
Number of pages11
JournalDevelopmental Neuroscience
Issue number4-5
StatePublished - Sep 1 2022


  • Cerebral palsy
  • Chorioamnionitis
  • Encephalopathy of prematurity
  • Gait
  • Motor

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience


Dive into the research topics of 'Infantile Cocktail of Erythropoietin and Melatonin Restores Gait in Adult Rats with Preterm Brain Injury'. Together they form a unique fingerprint.

Cite this