Abstract |
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.
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Authors | I Yatsiv, N Grigoriadis, C Simeonidou, P F Stahel, O I Schmidt, A G Alexandrovitch, J Tsenter, E Shohami |
Journal | FASEB journal : official publication of the Federation of American Societies for Experimental Biology
(FASEB J)
Vol. 19
Issue 12
Pg. 1701-3
(Oct 2005)
ISSN: 1530-6860 [Electronic] United States |
PMID | 16099948
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents
- CD11b Antigen
- CD18 Antigens
- Cytokines
- Glial Fibrillary Acidic Protein
- Recombinant Proteins
- Erythropoietin
- CASP3 protein, human
- Casp3 protein, mouse
- Casp3 protein, rat
- Caspase 3
- Caspases
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Topics |
- Animals
- Anti-Inflammatory Agents
(pharmacology)
- Apoptosis
- Axons
(metabolism)
- Brain
(pathology)
- CD11b Antigen
(biosynthesis)
- CD18 Antigens
(biosynthesis)
- Caspase 3
- Caspases
(metabolism)
- Cytokines
(metabolism)
- Disease Models, Animal
- Erythropoietin
(chemistry, metabolism, pharmacology, physiology)
- Glial Fibrillary Acidic Protein
(metabolism)
- Head Injuries, Closed
(pathology)
- Hematopoiesis
- Immunohistochemistry
- In Situ Nick-End Labeling
- Inflammation
- Male
- Mice
- Neurons
(metabolism, pathology)
- Rats
- Recombinant Proteins
(chemistry)
- Time Factors
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