Characterization of the pharmacokinetics of human recombinant erythropoietin in blood and brain when administered immediately after lateral fluid percussion brain injury and its pharmacodynamic effects on IL-1beta and MIP-2 in rats

Thomas Lieutaud, Peter J D Andrews, Jonathan K J Rhodes, Robert Williamson

Research output: Contribution to journalArticlepeer-review

Abstract

This study sought to determine the bio-availability of recombinant human erythropoietin (EPO) in the brain and blood and its effects on the cerebral concentrations of the inflammatory mediators interleukin-1beta (IL-1beta) and macrophage-inflammation protein-2 (MIP-2) following lateral fluid percussion brain injury (FPI) in the rat. After induction of moderate FPI (1.6-1.8 atm), EPO was injected intraperitoneally (IP) or intravenously (IV) at doses of 1000-5000 U/kg in a randomized and blinded manner. Animals were then sacrificed at time points (4, 8, 12, 24 h) post-trauma, and the brain concentrations of EPO, IL-1beta, and MIP-2 were determined. EPO administration leads to a dose-dependent increase in the brain concentration of the drug; however, this could only be detected at doses of 3000 and 5000 U/kg. The cerebral concentration peaked in the first 4 h following trauma. EPO concentrations were significantly higher and decreased more slowly in the traumatized cortex compared to the contralateral side (p
Original languageEnglish
Pages (from-to)1179-85
Number of pages7
JournalJournal of Neurotrauma
Volume25
Issue number10
DOIs
Publication statusPublished - Oct 2008

Keywords

  • Injections, Intraperitoneal
  • Animals
  • Drug Administration Schedule
  • Injections, Intravenous
  • Recombinant Proteins
  • Dose-Response Relationship, Drug
  • Humans
  • Brain
  • Interleukin-1beta
  • Disease Models, Animal
  • Encephalitis
  • Rats
  • Rats, Sprague-Dawley
  • Down-Regulation
  • Erythropoietin
  • Chemokine CXCL2
  • Brain Injuries
  • Time Factors
  • Male
  • Functional Laterality
  • Blood-Brain Barrier

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