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

doi:10.1089/neu.2008.0591

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 journal › Article › peer-review

Abstract / Description of output

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 language	English
Pages (from-to)	1179-85
Number of pages	7
Journal	Journal of Neurotrauma
Volume	25
Issue number	10
DOIs	https://doi.org/10.1089/neu.2008.0591
Publication status	Published - Oct 2008

Keywords / Materials (for Non-textual outputs)

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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Lieutaud, T., Andrews, P. J. D., Rhodes, J. K. J., & Williamson, R. (2008). 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. Journal of Neurotrauma, 25(10), 1179-85. https://doi.org/10.1089/neu.2008.0591

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title = "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",

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",

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",

author = "Thomas Lieutaud and Andrews, {Peter J D} and Rhodes, {Jonathan K J} and Robert Williamson",

year = "2008",

month = oct,

doi = "10.1089/neu.2008.0591",

language = "English",

volume = "25",

pages = "1179--85",

journal = "Journal of Neurotrauma",

issn = "0897-7151",

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Lieutaud, T, Andrews, PJD, Rhodes, JKJ & Williamson, R 2008, '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', Journal of Neurotrauma, vol. 25, no. 10, pp. 1179-85. https://doi.org/10.1089/neu.2008.0591

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. / Lieutaud, Thomas; Andrews, Peter J D; Rhodes, Jonathan K J et al.
In: Journal of Neurotrauma, Vol. 25, No. 10, 10.2008, p. 1179-85.

Research output: Contribution to journal › Article › peer-review

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T1 - 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

AU - Lieutaud, Thomas

AU - Andrews, Peter J D

AU - Rhodes, Jonathan K J

AU - Williamson, Robert

PY - 2008/10

Y1 - 2008/10

N2 - 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

AB - 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

KW - Injections, Intraperitoneal

KW - Animals

KW - Drug Administration Schedule

KW - Injections, Intravenous

KW - Recombinant Proteins

KW - Dose-Response Relationship, Drug

KW - Humans

KW - Brain

KW - Interleukin-1beta

KW - Disease Models, Animal

KW - Encephalitis

KW - Rats

KW - Rats, Sprague-Dawley

KW - Down-Regulation

KW - Erythropoietin

KW - Chemokine CXCL2

KW - Brain Injuries

KW - Time Factors

KW - Male

KW - Functional Laterality

KW - Blood-Brain Barrier

U2 - 10.1089/neu.2008.0591

DO - 10.1089/neu.2008.0591

M3 - Article

C2 - 18842103

SN - 0897-7151

VL - 25

SP - 1179

EP - 1185

JO - Journal of Neurotrauma

JF - Journal of Neurotrauma

IS - 10

ER -