Infantile Cocktail of Erythropoietin and Melatonin Restores Gait in Adult Rats with Preterm Brain Injury.
Cerebral palsy
Chorioamnionitis
Encephalopathy of prematurity
Gait
Motor
Journal
Developmental neuroscience
ISSN: 1421-9859
Titre abrégé: Dev Neurosci
Pays: Switzerland
ID NLM: 7809375
Informations de publication
Date de publication:
2022
2022
Historique:
received:
13
12
2021
accepted:
11
03
2022
pubmed:
1
4
2022
medline:
15
9
2022
entrez:
31
3
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35358965
pii: 000524394
doi: 10.1159/000524394
pmc: PMC10066804
mid: NIHMS1795407
doi:
Substances chimiques
Erythropoietin
11096-26-7
Melatonin
JL5DK93RCL
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
266-276Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL139492
Pays : United States
Informations de copyright
© 2022 S. Karger AG, Basel.
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