Treatment of traumatic brain injury in rats with erythropoietin and carbamylated erythropoietin.
OBJECTIVE
This study was designed to investigate the neuroprotective properties of recombinant erythropoietin (EPO) and carbamylated erythropoietin (CEPO) administered following traumatic brain injury (TBI) in rats.


METHODS
Sixty adult male Wistar rats were injured with controlled cortical impact, and then EPO, CEPO, or a placebo (phosphate-buffered saline) was injected intraperitoneally. These injections were performed either 6 or 24 hours after TBI. To label newly regenerating cells, bromodeoxyuridine was injected intraperitoneally for 14 days after TBI. Blood samples were obtained on Days 1, 2, 3, 7, 14, and 35 to measure hematocrit. Spatial learning was tested using the Morris water maze. All rats were killed 35 days after TBI. Brain sections were immunostained as well as processed for the enzyme-linked immunosorbent assay to measure brain-derived neurotrophic factor (BDNF).


RESULTS
A statistically significant improvement in spatial learning was seen in rats treated with either EPO or CEPO 6 or 24 hours after TBI (p < 0.05); there was no difference in the effects of EPO and CEPO. Also, these drugs were equally effective in increasing the number of newly proliferating cells within the dentate gyrus at both time points. A statistically significant increase in BDNF expression was seen in animals treated with both EPO derivatives at 6 or 24 hours after TBI. Systemic hematocrit was significantly increased at 48 hours and 1 and 2 weeks after treatment with EPO but not with CEPO.


CONCLUSIONS
These data demonstrate that at the doses used, EPO and CEPO are equally effective in enhancing spatial learning and promoting neural plasticity after TBI.
Mahmood
Asim
A
Department of Neurosurgery, Henry Ford Health System, Detroit, Michigan 48202, USA. nsaam@neuro.hfh.edu
Lu
Dunyue
D
Qu
Changsheng
C
Goussev
Anton
A
Zhang
Zheng Gang
ZG
Lu
Chang
C
Chopp
Michael
M
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006400:Hematocrit; D007274:Injections, Intraperitoneal; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins
D019208:Brain-Derived Neurotrophic Factor; D011994:Recombinant Proteins; C488171:carbamylated erythropoietin; D004921:Erythropoietin