Expression of Progranulin in a Mouse Model of Newborn Hypoxic-ischemic Brain Damage

摘要

Neonatal hypoxic ischemic encephalopathy (HIE) is one of the main reasons of death and disability in neonatal, for lack of blood and oxygen during the time of birth. Progranulin (PGRN) as a neurotrophic factor is extensively expressed in the brain can regulate neurite growth and promote neuronal survival. The mutations of PGRN gene may contribute to frontotemporal dementia (FTD). However, the role of PGRN in neonatal HIE remains unclear. We designed this study to investigate the changes of PGRN expression in the brain of newborn mice at different time points after hypoxic -ischemic brain damage (HIBD). Postnatal 7day (P7) mouse pups were induced HIBD model by the method of Rice with some improvement. TTC was used to detect the ischemic lesion volume. The localization of PGRN brain cells was detected by immunofluorescence. We also used Western blotting to measure the expression level of PGRN at different days (1, 3, 7 days) following HIBD. The results showed that we established the HIIBD model successfully. PGRN was primarily expressed in neurons and microglia, but rarely in astrocytes. In addition, PGRN expression in the brain of HIBD mice markedly increased at 1 day and 3 days and was restored at 7 days after HIBD. The results indicated that increased PGRN levels may be involved in the pathological mechanism and neural repair process of HIBD.