关键词: 缺血；　周围白质软化；　未成熟脑白质；　谷氨酸；　异常信号传输

Abstract: 　Objective　To explore the damage of ischemia-induced abnormal glutamate signal transduction on immature white matter. Method　Oligodendrocyte (OL) precursor oxygen-glucose deprivation (OGD) cell model and ischemic periventricular leukomalacia (PVL) animal model were prepared in 2-day-old neonatal rats. Cells and supernatants were collected 24 hours after OGD. Extracellular glutamate concentration of OL precursor was measured by high performance liquid chromatography, and intracellular calcium concentration and apoptotic rate of OL precursor were measured by flow cytometry. Neonatal rats were sacrificed on the 5th day after the establishment of the model. The pathological evaluation of white matter were performed by light microscopy, and myelin basic protein (MBP) positive mature OL were detected by immunohistochemistry and the myelination of white matter was evaluated by electron microscopy. Results　In vitro, compared with the normal OL precursors deprived of anaerobic sugar, OL precursors in OGD group showed significant accumulation of extracellular glutamate (P<0.01), the significantly increased intracellular calcium concentration (P<0.01), and the significantly increased apoptosis rate and necrosis rate of OL precursors (P<0.01, P<0.05). In vivo, compared with normal newborn rats in sham group, all rats in PVL group showed mild or severe pathological changes in white matter, MBP positive mature OL in white matter was significantly reduced, and myelin formation was also malformed, which was manifested as significantly reduced number of myelin sheath and significantly thinner myelin sheath thickness (all P<0.01). Conclusions　Immature white matter has the glutamate signaling characteristics similar to that of mature white matter. Ischemia induces abnormal signal transmission of glutamate in immature white matter.

Key words: 　ischemia;　peripheral leukomalacia;　immature white matter;　glutamate;　abnormal signal transduction