Neuroprotective effects of erythropoietin on acute metabolic and pathological changes in experimentally induced neurotrauma

Laboratory investigation

Chad E. Hartley, Madhu Varma, John P. Fischer, Richard Riccardi, Judith A. Strauss, Sejal M Shah, Shengle Zhang, Zhong Jin Yang

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Object. Head trauma is a dynamic process characterized by a cascade of metabolic and molecular events. Erythropoietin (EPO) has been shown to have neuroprotective effects in animal models of traumatic brain injury (TBI). Acute in vivo mechanisms and pathological changes associated with EPO following TBI are unknown. In this study the authors compare acute metabolic and pathological changes following TBI with and without systemically administered EPO. Methods. Right frontal lobe microdialysis cannulae and right parietal lobe percussion hubs were inserted into 16 Sprague-Dawley rats. After a 4- to 5-day recovery, TBI was induced via a DragonFly fluid-percussion device at 2.5-2.8 atm. Rats were randomized into 2 groups, which received 5000 U/kg EPO or normal saline intraperitoneally 30 minutes after TBI. Microdialysis samples for glucose, lactate, pyruvate, and glutamate were obtained every 25 minutes for 10 hours. Rats were killed, their brains processed for light microscopy, and sections stained with H & E. Results. Erythropoietin administered 30 minutes after TBI directly affects acute brain metabolism. Brains treated with EPO maintain higher levels of glucose 4-10 hours after TBI (p <0.01), lower levels of lactate 6-10 hours after TBI (p <0.01), and lower levels of pyruvate 7.5-10 hours after TBI (p <0.01) compared with saline-treated controls. Erythropoietin maintains aerobic metabolism after TBI. Systemic EPO administration reduces acute TBI-induced lesion volume (p <0.05). Conclusions. Following TBI, neuron use initially increases, with subsequent depletion of extracellular glucose, resulting in increased levels of extracellular lactate and pyruvate. This energy requirement can result in cell death due to increased metabolic demands. These data suggest that the neuroprotective effect of EPO may be partially due to improved energy metabolism in the acute phase in this rat model of TBI.

Original languageEnglish (US)
Pages (from-to)708-714
Number of pages7
JournalJournal of Neurosurgery
Volume109
Issue number4
DOIs
StatePublished - Oct 2008
Externally publishedYes

Fingerprint

Neuroprotective Agents
Erythropoietin
Pyruvic Acid
Percussion
Lactic Acid
Microdialysis
Glucose
Traumatic Brain Injury
Brain
Odonata
Parietal Lobe
Frontal Lobe
Craniocerebral Trauma
Brain Injuries
Energy Metabolism
Sprague Dawley Rats
Glutamic Acid
Microscopy
Cell Death
Animal Models

Keywords

  • Erythropoietin
  • Microdialysis
  • Neuroprotection
  • Rat
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Neuroprotective effects of erythropoietin on acute metabolic and pathological changes in experimentally induced neurotrauma : Laboratory investigation. / Hartley, Chad E.; Varma, Madhu; Fischer, John P.; Riccardi, Richard; Strauss, Judith A.; Shah, Sejal M; Zhang, Shengle; Yang, Zhong Jin.

In: Journal of Neurosurgery, Vol. 109, No. 4, 10.2008, p. 708-714.

Research output: Contribution to journalArticle

Hartley, Chad E. ; Varma, Madhu ; Fischer, John P. ; Riccardi, Richard ; Strauss, Judith A. ; Shah, Sejal M ; Zhang, Shengle ; Yang, Zhong Jin. / Neuroprotective effects of erythropoietin on acute metabolic and pathological changes in experimentally induced neurotrauma : Laboratory investigation. In: Journal of Neurosurgery. 2008 ; Vol. 109, No. 4. pp. 708-714.
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abstract = "Object. Head trauma is a dynamic process characterized by a cascade of metabolic and molecular events. Erythropoietin (EPO) has been shown to have neuroprotective effects in animal models of traumatic brain injury (TBI). Acute in vivo mechanisms and pathological changes associated with EPO following TBI are unknown. In this study the authors compare acute metabolic and pathological changes following TBI with and without systemically administered EPO. Methods. Right frontal lobe microdialysis cannulae and right parietal lobe percussion hubs were inserted into 16 Sprague-Dawley rats. After a 4- to 5-day recovery, TBI was induced via a DragonFly fluid-percussion device at 2.5-2.8 atm. Rats were randomized into 2 groups, which received 5000 U/kg EPO or normal saline intraperitoneally 30 minutes after TBI. Microdialysis samples for glucose, lactate, pyruvate, and glutamate were obtained every 25 minutes for 10 hours. Rats were killed, their brains processed for light microscopy, and sections stained with H & E. Results. Erythropoietin administered 30 minutes after TBI directly affects acute brain metabolism. Brains treated with EPO maintain higher levels of glucose 4-10 hours after TBI (p <0.01), lower levels of lactate 6-10 hours after TBI (p <0.01), and lower levels of pyruvate 7.5-10 hours after TBI (p <0.01) compared with saline-treated controls. Erythropoietin maintains aerobic metabolism after TBI. Systemic EPO administration reduces acute TBI-induced lesion volume (p <0.05). Conclusions. Following TBI, neuron use initially increases, with subsequent depletion of extracellular glucose, resulting in increased levels of extracellular lactate and pyruvate. This energy requirement can result in cell death due to increased metabolic demands. These data suggest that the neuroprotective effect of EPO may be partially due to improved energy metabolism in the acute phase in this rat model of TBI.",
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T2 - Laboratory investigation

AU - Hartley, Chad E.

AU - Varma, Madhu

AU - Fischer, John P.

AU - Riccardi, Richard

AU - Strauss, Judith A.

AU - Shah, Sejal M

AU - Zhang, Shengle

AU - Yang, Zhong Jin

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N2 - Object. Head trauma is a dynamic process characterized by a cascade of metabolic and molecular events. Erythropoietin (EPO) has been shown to have neuroprotective effects in animal models of traumatic brain injury (TBI). Acute in vivo mechanisms and pathological changes associated with EPO following TBI are unknown. In this study the authors compare acute metabolic and pathological changes following TBI with and without systemically administered EPO. Methods. Right frontal lobe microdialysis cannulae and right parietal lobe percussion hubs were inserted into 16 Sprague-Dawley rats. After a 4- to 5-day recovery, TBI was induced via a DragonFly fluid-percussion device at 2.5-2.8 atm. Rats were randomized into 2 groups, which received 5000 U/kg EPO or normal saline intraperitoneally 30 minutes after TBI. Microdialysis samples for glucose, lactate, pyruvate, and glutamate were obtained every 25 minutes for 10 hours. Rats were killed, their brains processed for light microscopy, and sections stained with H & E. Results. Erythropoietin administered 30 minutes after TBI directly affects acute brain metabolism. Brains treated with EPO maintain higher levels of glucose 4-10 hours after TBI (p <0.01), lower levels of lactate 6-10 hours after TBI (p <0.01), and lower levels of pyruvate 7.5-10 hours after TBI (p <0.01) compared with saline-treated controls. Erythropoietin maintains aerobic metabolism after TBI. Systemic EPO administration reduces acute TBI-induced lesion volume (p <0.05). Conclusions. Following TBI, neuron use initially increases, with subsequent depletion of extracellular glucose, resulting in increased levels of extracellular lactate and pyruvate. This energy requirement can result in cell death due to increased metabolic demands. These data suggest that the neuroprotective effect of EPO may be partially due to improved energy metabolism in the acute phase in this rat model of TBI.

AB - Object. Head trauma is a dynamic process characterized by a cascade of metabolic and molecular events. Erythropoietin (EPO) has been shown to have neuroprotective effects in animal models of traumatic brain injury (TBI). Acute in vivo mechanisms and pathological changes associated with EPO following TBI are unknown. In this study the authors compare acute metabolic and pathological changes following TBI with and without systemically administered EPO. Methods. Right frontal lobe microdialysis cannulae and right parietal lobe percussion hubs were inserted into 16 Sprague-Dawley rats. After a 4- to 5-day recovery, TBI was induced via a DragonFly fluid-percussion device at 2.5-2.8 atm. Rats were randomized into 2 groups, which received 5000 U/kg EPO or normal saline intraperitoneally 30 minutes after TBI. Microdialysis samples for glucose, lactate, pyruvate, and glutamate were obtained every 25 minutes for 10 hours. Rats were killed, their brains processed for light microscopy, and sections stained with H & E. Results. Erythropoietin administered 30 minutes after TBI directly affects acute brain metabolism. Brains treated with EPO maintain higher levels of glucose 4-10 hours after TBI (p <0.01), lower levels of lactate 6-10 hours after TBI (p <0.01), and lower levels of pyruvate 7.5-10 hours after TBI (p <0.01) compared with saline-treated controls. Erythropoietin maintains aerobic metabolism after TBI. Systemic EPO administration reduces acute TBI-induced lesion volume (p <0.05). Conclusions. Following TBI, neuron use initially increases, with subsequent depletion of extracellular glucose, resulting in increased levels of extracellular lactate and pyruvate. This energy requirement can result in cell death due to increased metabolic demands. These data suggest that the neuroprotective effect of EPO may be partially due to improved energy metabolism in the acute phase in this rat model of TBI.

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