Abstract
Selective vulnerability of late oligodendrocyte progenitors (preOLs: NG2-positive and O4-positive cells) to hypoxic-ischemia (H-I) was reported, explaining the etiology of periventricular leukomalacia (PVL). In rats, preOLs is detected in white matter at postnatal day 2 (P2)-P4. To investigate whether H-I targeting to preOLs caused pathological changes more similar to PVL and whether erythropoietin (EPO) has effect to reduce brain damage by H-I, right common carotid artery occlusion (RCAO) was carried out in P2-P4 rats followed by hypoxic condition (6% 02) for various time (0-90 min). RCAO with 6% O2 for 60 min resulted in high proportion of death: 64% in P2, 50% in P3, and 89% in P4. Histological examination 2 days after H-I revealed that no obvious change was shown in P2 rats. However, typical histological changes of PVL were found in most of surviving P3 rats, suggesting that RCAO followed by 6% 02 for 60 min in P3 pups induced histological changes more similar to human PVL in P3 pups. Various dose of EPO (1-30,000 U/kg, i.p.) was treated to animals just before H-I, and the mortality and histological alterations were assessed. With lower concentration of EPO (50-100 U/kg), death rate became to 27-38%, and the damage in cortical and callosal white matter was decreased, indicating that low dose of EPO is protective to cerebral white matter damage in P3 rats. [J Physiol Sci. 2006;56 Suppl:S212]
