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Erythropoietin is neuroprotective, improves functional recovery, and reduces neuronal apoptosis and inflammation in a rodent model of experimental closed head injury
Author(s) -
Yatsiv Ido,
Grigoriadis Nikolas,
Simeonidou Constantina,
Stahel Philip F.,
Schmidt Oliver I.,
Alexandrovich Alexander G.,
Tsenter Jeanna,
Shohami Esther
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-3907fje
Subject(s) - neuroprotection , erythropoietin , medicine , traumatic brain injury , inflammation , closed head injury , brain damage , apoptosis , pharmacology , neuroscience , immunology , biology , biochemistry , psychiatry
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in young people in industrialized countries. Although various anti‐inflammatory and antiapoptotic modalities have shown neuroprotective effects in experimental models of TBI, to date, no specific pharmacological agent aimed at blocking the progression of secondary brain damage has been approved for clinical use. Erythropoietin (Epo) belongs to the cytokine superfamily and has traditionally been viewed as a hematopoiesis‐regulating hormone. The newly discovered neuroprotective properties of Epo lead us to investigate its effect in TBI in a mouse model of closed head injury. Recombinant human erythropoietin (rhEpo) was injected at 1 and 24 h after TBI, and the effect on recovery of motor and cognitive functions, tissue inflammation, axonal degeneration, and apoptosis was evaluated up to 14 days. Motor deficits were lower, cognitive function was restored faster, and less apoptotic neurons and caspase‐3 expression were found in rhEpo‐treated as compared with vehicle‐treated animals ( P <0.05). Axons at the trauma area in rhEpo‐treated mice were relatively well preserved compared with controls (shown by their density; P< 0.01). Immunohistochemical analysis revealed a reduced activation of glial cells by staining for GFAP and complement receptor type 3 (CD11b/CD18) in the injured hemisphere of Epo‐ vs. vehicle‐treated animals. We propose that further studies on Epo in TBI should be conducted in order to consider it as a novel therapy for TBI.