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

Xuxin Ren,Mengxia Wang,Jing Liu,Li Luo,Xing Tu,Qiaoli Ren,Wei Liu,Wenyan Zhao,Guoying Li,Yilin Liu,Junhua Yang

doi:10.11648/j.ajp.20190503.23

Abstract

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.

Highlights

PGRN, acknowledged as Granulin-Epithelin Precursor (GEP), is a 68∼88-kDa multifunctional protein, which can be found in epithelial and immune cells, neurons and adipocytes [1]
Despite all the above factors have certain positive effects in animal models have been proven, we still not clear which growth factors have the best brain protection and repair functionThe previous research shown that PGRN as a neurotrophic factor exerts a enormous function on the early development of neurons and the mutational of the PGRN gene (GRN) resulting in partial or complete loss of the PGRN protein were reported to associate with frontotemporal dementia (FTD) [23,24]
The expression of PGRN in microglia cells increased significantly when traumatic brain injury (TBI), toxin-induced brain injuries, spinal cord injury and nerve axotomy occurred [37, 38, 39, 40, 41] In the focal cerebral ischemia-reperfusion injury, the absence of PGRN will promote the destruction of the blood-brain barrier (BBB) [26] and giving exogenous recombinant-PGRN (R-PGRN) can significantly reduce the size of the infarct by inhibiting recruitment of neutrophils [27]

Summary

Introduction

PGRN, acknowledged as Granulin-Epithelin Precursor (GEP), is a 68∼88-kDa multifunctional protein, which can be found in epithelial and immune cells, neurons and adipocytes [1]. In the brain, the frontotemporal dementia (FTD) and neuronal ceroid lipofuscinosis (NCL) are associated with the loss of the PGRN protein, due to a mutation of the PGRN gene (GRN) [3]. Van Damme P reported that PGRN could upgrade the survival of neurons, promote neural progenitor proliferation in vitro [7]. These studies show that PGRN was a neurotrophic factor, especially during the early development of neural and long-term neuronal survival

Methods

Discussion

Conclusion