Erythropoietin reduces hippocampus injury in neonatal rats with hypoxic ischemic brain damage via targeting matrix metalloprotein-2.

OBJECTIVE Erythropoietin (EPO), as a type of the tissue-protective cytokines, is a 30.4 kDa hematopoietic glycoprotein. The purpose of this study was to explore the neuroprotective effects of EPO on the neonatal hypoxic-ischemic-induced hippocampus injury and the MMP-2 expression. MATERIALS AND METHODS Neonatal Sprague-Dawley (SD) rats were randomly divided into an untreated group (control) and two hypoxia-ischemia (HI) groups treated with saline control or EPO. Hippocampi were harvested at various times after return to normoxia (6 h, 24 h, 3 days and 7 days post-HI) for analyses of infarct areas and expression using histology, Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS EPO injections reduced the infarction and loss of brain tissue. HI group exhibited an enhanced MMP-2 positive staining compared to controls at 24 h, 3 and 7 days post-HI by immunohistochemistry. These results were confirmed by Western blot analysis of MMP-2 expression at 7 days post-HI. Levels of MMP-2 mRNA in the injured hippocampi increased significantly at 24 h and 7 days post-HI. In particular, the EPO treatment further significantly enhanced this increase. CONCLUSIONS EPO protected hypoxic-ischemic-induced neonatal brain damage by up-regulating the MMP-2 expression. Hence, systemic EPO may have potential utility for the treatment of HI injury in human newborns.