[基础医学]读书报告.ppt

Timing of appearance of late oligodendrocyteprogenitors coincides with enhancedsusceptibility of preterm rabbit cerebral whitematter to hypoxia-ischemia HYPOEHESIEZ? Premature infants are susceptible to both cerebral white and gray matter injury. In a fetal rabbit model of placental insufficiency, preterm rabbits at E22 exhibited histologic evidence of gray matter injury but minimal white matter injury after global H-I. Hypothesize: the dissociation between susceptibility to gray and white matter injury at E22 was related to the timing of appearance of late oligodendrocyte progenitors (preOLs) that are particularly vulnerable in preterm human white matter lesions Introduction PWMI is the major form of brain injury and the leading cause of CL and cognitive deficits in survivors of premature birth Immature human cerebral white matter is particularly susceptible to oxidative damage of a magnitude consistent with hypoxia-ischemia (H-I) Within white matter lesions, the oligodendrocyte (OL) lineage shows maturationdependent vulnerability(易损性) to cerebral H-I Introduction Four successive stages of the OL lineage OL progenitors (NG2+, Olig2+, O4-) Preoligodendrocytes (preOLs) (O4+O1-) immature OLs (O4+O1+) mature OLs (MBP+) The predominant expression of preOLs coincides with the high-risk period for PWMI . PreOLs are selectively vulnerable to oxidative stress Introduction Whether injury from H-I would occur if white matter were deficient in susceptible OL precursors？ To address this fundamental question in the fetus, we used a rabbit placental insufficiency model that generates global fetal H-I. Compared with the postnatal rodent, the fetal rabbit brain is larger, has more prominent white matter tracts, myelinates(髓鞘化) in a similar perinatal time course to human, and maturation of OLs begins antenatally. Materials and methods timed-pregnant New Zeala