TY - JOUR
T1 - Neuroprotective effects of erythropoietin on acute metabolic and pathological changes in experimentally induced neurotrauma
T2 - Laboratory investigation
AU - Hartley, Chad E.
AU - Varma, Madhu
AU - Fischer, John P.
AU - Riccardi, Richard
AU - Strauss, Judith A.
AU - Shah, Sejal
AU - Zhang, Shengle
AU - Yang, Zhong Jin
PY - 2008/10
Y1 - 2008/10
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.
KW - Erythropoietin
KW - Microdialysis
KW - Neuroprotection
KW - Rat
KW - Traumatic brain injury
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U2 - 10.3171/JNS/2008/109/10/0708
DO - 10.3171/JNS/2008/109/10/0708
M3 - Article
C2 - 18826359
AN - SCOPUS:55949090879
SN - 0022-3085
VL - 109
SP - 708
EP - 714
JO - Journal of neurosurgery
JF - Journal of neurosurgery
IS - 4
ER -