The Changes of Tissue-Type Plasminogen Activator and Matrix Metalloproteinases in Neonatal Mice with Hypoxic-Ischemic Encephalopathy

Abstract

Fetal distress and neonatal asphyxia are key factors which result in neonatal hypoxic-ischemic encephalopathy (HIE). There is growing evidence that tissue-type plasminogen activator (TPA) and matrix metalloproteinases (MMPs) may be involved in extracellular matrix (ECM) degradation in the central nervous system. In this study, the transmission electron microscope was used to observe the growth and development characteristics of the blood-brain barrier (BBB), follow by the activity of TPA and the expression of MMPs in HIE model were detected. The asphyxia in female mice within the last day of gestation was produced by a delayed cesarean section. The experiment was designed for 1 control group and 2 asphyctic groups (15min and 30min), then the activities of TPA and expression of MMPs were detected separately. The results showed that the BBB was not fully developed in newborns, their brain microvascular endothelial cells were not surrounded with intact basement membrane and only had discontinuous basement membrane-like materials of varying thickness. The activity of TPA and the expression of MMPs of brain increased after hypoxia-ischemia in vivo. Based on these findings we concluded that the basement membrane at the BBB was a weak link in the brain, TPA and MMPs could degrade components of the ECM. So these enzymes increased after hypoxia-ischemia might be able to attack the basement membrane of microvessels, then open the BBB and induce the cerebral edema.