Quantitative analysis of perinatal rodent oligodendrocyte lineage progression and its correlation with human

The development of a rodent model in the perinatal rat or mouse that reproduces the principal features of human perinatal white matter injury (periventricular leukomalacia) has been hampered by uncertainty about the developmental window in the rodent that coincides temporally with cerebral white matter development in the premature infant. We recently determined oligodendrocyte (OL) lineage progression in human cerebral white matter and found that the late OL progenitor (preOL) predominates throughout the high-risk period for periventricular leukomalacia [J. Neurosci. 21(2001), 1302-1312]. Here, we determined in the perinatal rat and mouse when each species displays a distribution of OL stages that is similar to the premature human cerebral white matter. PreOLs are abundant in the rat and mouse at P2. By P7, extensive OL maturation occurs in both species and coincides with the onset of early myelination. PreOLs and immature OLs mature in the P2 white matter along a medial to lateral gradient. This may provide an explanation for regional variation in the susceptibility of perinatal white matter to injury. We propose that the sequence of OL lineage progression is a useful means to estimate developmental windows of white matter maturation in perinatal rodents that coincide with those of developing human cerebral white matter. These studies support that the vulnerable period for white matter injury in the rodent is centered around P2 and should decline thereafter, coincident with the onset of myelination.