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Developmental Neuroscience
Jantzie L.a,b,c,d· Muthukumar S.a· Kitase Y.b· Vasan V.a· Fouda M.A.a· Hamimi S.a,b· Burkhardt C.b· Burton V.J.c,e· Gerner G.e· Scafidi J.c,e· Ye X.a· Northington F.J.b· Robinson S.a,b,caDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
bDepartment of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
cDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
dDepartment of Neurology, Kennedy Krieger Institute, Baltimore, MD, USA
eCenter for Infant Neurodevelopment, Kennedy Krieger Institute, Baltimore, MD, USA
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Article / Publication DetailsFirst-Page Preview
Received: December 13, 2021
Accepted: March 11, 2022
Published online: March 31, 2022
Number of Print Pages: 11
Number of Figures: 5
Number of Tables: 1
ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)
For additional information: https://www.karger.com/DNE
AbstractCerebral 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.
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Received: December 13, 2021
Accepted: March 11, 2022
Published online: March 31, 2022
Number of Print Pages: 11
Number of Figures: 5
Number of Tables: 1
ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)
For additional information: https://www.karger.com/DNE
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