Role of gender in outcome after traumatic brain injury and therapeutic effect of erythropoietin in mice.
The aim of this study was to investigate the role of gender in histological and functional outcome, angiogenesis, neurogenesis and therapeutic effects of recombinant human erythropoietin (rhEPO) in mice after traumatic brain injury (TBI). TBI caused both tissue loss in the cortex and cell loss in the dentate gyrus (DG) in the injured hemisphere at day 35 post TBI without a significant gender difference. After TBI, sensorimotor deficits were significantly larger in male mice compared to females, while similar spatial learning deficits were present in both genders. TBI alone significantly stimulated angiogenesis and neurogenesis in the cortex and in the DG of injured hemispheres in both genders. rhEPO at a dose of 5000 units/kg body weight administered intraperitoneally at 6 h, and 3 and 7 days after injury significantly reduced lesion volume and DG cell loss examined at day 35 after TBI as well as dramatically improved sensorimotor and spatial learning performance without an obvious gender proclivity. rhEPO significantly enhanced neurogenesis in the cortex and the DG of the ipsilateral hemisphere in male TBI mice. rhEPO did not affect angiogenesis in the ipsilateral cortex and DG in both genders after TBI. The present data demonstrate that posttraumatic administration of rhEPO improves histological and functional outcome in both genders, which may be mediated by reducing cortical tissue damage and DG cell loss in the ipsilateral hemisphere. In addition, the major gender propensity observed in the present study with mice after TBI without treatment is limited to sensorimotor deficits and cell proliferation.
Xiong
Ye
Y
Department of Neurosurgery, Henry Ford Health System, 2799 West Grand Boulevard, Detroit, MI 48202, USA.
Mahmood
Asim
A
Lu
Dunyue
D
Qu
Changsheng
C
Goussev
Anton
A
Schallert
Timothy
T
Chopp
Michael
M
D000818:Animals; D001522:Behavior, Animal; D001930:Brain Injuries / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D018891:Dentate Gyrus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D020233:Gait Disorders, Neurologic / Q000188:drug therapy / Q000209:etiology; D007859:Learning Disabilities / Q000188:drug therapy / Q000209:etiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000209:etiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011994:Recombinant Proteins; D012727:Sex Characteristics; D013997:Time Factors
D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine