Document Detail

Evaluation of the therapeutic benefit of delayed administration of erythropoietin following early hypoxic-ischemic injury in rodents.
MedLine Citation:
PMID:  23328535     Owner:  NLM     Status:  MEDLINE    
Hypoxia-ischemia (HI) and associated brain injuries are seen in premature as well as term infants with birth complications. The resulting impairments involve deficits in many cognitive domains, including language development. Poor rapid auditory processing is hypothesized to be one possible underlying factor leading to subsequent language delays. Mild hypothermia treatment for HI injuries in term infants is widely used as an intervention but can be costly and time consuming. Data suggest that the effectiveness of hypothermia treatment following HI injury declines beyond 6 h following injury. Consequently, the availability of a therapeutic alternative without these limitations could allow doctors to treat HI-injured infants more effectively and thus reduce deleterious cognitive and language outcomes. Evidence from both human studies and animal models of neonatal HI suggests that erythropoietin (Epo), an endogenous cytokine hormone, may be a therapeutic agent that can ameliorate HI brain injury and preserve subsequent cognitive development and function. The current study sought to investigate the therapeutic effectiveness of Epo when administered immediately after HI injury, or delayed at intervals following the injury, in neonatal rodents. Rat pups received an induced HI injury on postnatal day 7, followed by an intraperitoneal injection of Epo (1,000 U/kg) immediately, 60 min, or 180 min following induction of injury. Subjects were tested on rapid auditory processing tasks in juvenile (P38-42) and adult periods (P80-85). Ventricular and cortical size was also measured from post mortem tissue. Results from the current study show a therapeutic benefit of Epo when given immediately following induction of HI injury, with diminished benefit from a 60-min-delayed injection of Epo and no protection following a 180-min-delayed injection. The current data thus show that the effectiveness of a single dose of Epo in ameliorating auditory processing deficits following HI injury decreases precipitously as treatment is delayed following injury. These data may have important implications for experimental human neonatal intervention with Epo.
M L Alexander; C A Hill; T S Rosenkrantz; R H Fitch
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-10
Journal Detail:
Title:  Developmental neuroscience     Volume:  34     ISSN:  1421-9859     ISO Abbreviation:  Dev. Neurosci.     Publication Date:  2012  
Date Detail:
Created Date:  2013-04-03     Completed Date:  2013-09-19     Revised Date:  2014-01-23    
Medline Journal Info:
Nlm Unique ID:  7809375     Medline TA:  Dev Neurosci     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  515-24     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 S. Karger AG, Basel.
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MeSH Terms
Animals, Newborn
Disease Models, Animal
Erythropoietin / administration & dosage*
Hypoxia-Ischemia, Brain / drug therapy*,  pathology
Neuroprotective Agents / administration & dosage*
Rats, Wistar
Grant Support
Reg. No./Substance:
0/Neuroprotective Agents; 11096-26-7/Erythropoietin

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