title: Erythropoietin attenuates the sequels of ischaemic spinal cord injury with enhanced recruitment of CD34+ cells in mice.
abstract: Erythropoietin has been shown to promote tissue regeneration after ischaemic injury in various organs. Here, we investigated whether Erythropoietin could ameliorate ischaemic spinal cord injury in the mouse and sought an underlying mechanism. Spinal cord ischaemia was developed by cross-clamping the descending thoracic aorta for 7 or 9 min. in mice. Erythropoietin (5000 IU/kg) or saline was administrated 30 min. before aortic cross-clamping. Neurological function was assessed using the paralysis score for 7 days after the operation. Spinal cords were histologically evaluated 2 and 7 days after the operation. Immunohistochemistry was used to detect CD34(+)  cells and the expression of brain-derived neurotrophic factor and vascular endothelial growth factor. Each mouse exhibited either mildly impaired function or complete paralysis at day 2. Erythropoietin-treated mice with complete paralysis demonstrated significant improvement of neurological function between day 2 and 7, compared to saline-treated mice with complete paralysis. Motor neurons in erythropoietin-treated mice were more preserved at day 7 than those in saline-treated mice with complete paralysis. CD34(+)  cells in the lumbar spinal cord of erythropoietin-treated mice were more abundant at day 2 than those of saline-treated mice. Brain-derived neurotrophic factor and vascular endothelial growth factor were markedly expressed in lumbar spinal cords in erythropoietin-treated mice at day 7. Erythropoietin demonstrated neuroprotective effects in the ischaemic spinal cord, improving neurological function and attenuating motor neuron loss. These effects may have been mediated by recruited CD34(+)  cells, and enhanced expression of brain-derived neurotrophic factor and vascular endothelial growth factor.
authors.affiliation: Department of Cardiac Surgery, University of Rostock, Rostock, Germany.
authors.forename: Koji
authors.initials: K
authors.lastname: Hirano
authors.forename: Klaus
authors.initials: K
authors.lastname: Wagner
authors.forename: Peter
authors.initials: P
authors.lastname: Mark
authors.forename: Erik
authors.initials: E
authors.lastname: Pittermann
authors.forename: Ralf
authors.initials: R
authors.lastname: Gäbel
authors.forename: Dario
authors.initials: D
authors.lastname: Furlani
authors.forename: Wenzhong
authors.initials: W
authors.lastname: Li
authors.forename: Brigitte
authors.initials: B
authors.lastname: Vollmar
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yamada
authors.forename: Gustav
authors.initials: G
authors.lastname: Steinhoff
authors.forename: Nan
authors.initials: N
authors.lastname: Ma
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020127:Recovery of Function / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D020760:Spinal Cord Ischemia / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34; D004921:Erythropoietin