Abstract
After completion of neuronal migration to form the cerebral cortex, axons undergo rapid elongation to their intraโ and subcortical targets, from midgestation through infancy. We define axonal development in the human parietal white matter in this critical period. Immunocytochemistry and Western blot analysis were performed on 46 normative cases from 20โ183 postconceptional (PC) weeks. AntiโSMI 312, a panโmarker of neurofilaments, stained axons as early as 23 weeks. AntiโSMI 32, a marker for nonphosphorylated neurofilament high molecular weight (NFH), primarily stained neuronal cell bodies (cortical, subcortical, and CajalโRetzius). AntiโSMI 31, which stains phosphorylated NFH, was used as a marker of axonal maturity, and showed relatively low levels of staining (approximately oneโfourth of adult levels) from 24โ34 PC weeks. GAPโ43, a marker of axonal growth and elongation, showed high levels of expression in the white matter from 21โ64 PC weeks and lower, adultโlike levels beyond 17 postnatal months. The onset of myelination, as seen by myelin basic protein expression, was โผ54 weeks, with progression to โadultโlikeโ staining by 72โ92 PC weeks. This study provides major insight into axonal maturation during a critical period of growth, over an age range not previously examined and one coinciding with the peak period of periventricular leukomalacia (PVL), the major disorder underlying cerebral palsy in premature infants. These data suggest that immature axons are susceptible to damage in PVL and that the timing of axonal maturation must be considered toward establishing its pathology relative to the oligodendrocyte/myelin/axonal unit. J. Comp. Neurol. 484:156โ167, 2005. ยฉ 2005 WileyโLiss, Inc.