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The Journal of Neuroscience, February 15, 2001, 21(4):1302-1312
Late Oligodendrocyte Progenitors Coincide with the Developmental
Window of Vulnerability for Human Perinatal White Matter Injury
Stephen A.
Back1, 3,
Ning Ling
Luo1,
Natalya S.
Borenstein3,
Joel M.
Levine2,
Joseph J.
Volpe3, and
Hannah C.
Kinney3, 4
1 Department of Pediatrics, Oregon Health Sciences
University, Portland, Oregon 97201, 2 Department of
Neurobiology and Behavior, State University of New York, Stony Brook,
New York 11794, and the Departments of 3 Neurology and
4 Pathology, Children's Hospital and Harvard Medical
School, Boston, Massachusetts 02115
Hypoxic-ischemic injury to the periventricular cerebral white
matter [periventricular leukomalacia (PVL)] results in cerebral palsy
and is the leading cause of brain injury in premature infants. The
principal feature of PVL is a chronic disturbance of myelination and
suggests that oligodendrocyte (OL) lineage progression is disrupted by
ischemic injury. We determined the OL lineage stages at risk for injury
during the developmental window of vulnerability for PVL (23-32 weeks,
postconceptional age). In 26 normal control autopsy human brains, OL
lineage progression was defined in parietal white matter, a region of
predilection for PVL. Three successive OL stages, the late OL
progenitor, the immature OL, and the mature OL, were characterized
between 18 and 41 weeks with anti-NG2 proteoglycan, O4, O1, and
anti-myelin basic protein (anti-MBP) antibodies. NG2+O4+ late OL
progenitors were the predominant stage throughout the latter half of
gestation. Between 18 and 27 weeks, O4+O1+ immature OLs were a minor
population (9.9 ± 2.1% of total OLs; n = 9). Between 28 and 41 weeks, an increase in immature OLs to 30.9 ± 2.1% of total OLs (n = 9) was accompanied by a
progressive increase in MBP+ myelin sheaths that were restricted to the
periventricular white matter. The developmental window of high risk for
PVL thus precedes the onset of myelination and identifies the late OL
progenitor as the major potential target. Moreover, the decline in
incidence of PVL at ~32 weeks coincides with the onset of myelination
in the periventricular white matter and suggests that the risk for PVL
is related to the presence of late OL progenitors in the
periventricular white matter.
Key words:
development; cell lineage; cerebral white matter; cerebral cortex; myelination; O4 antibody; O1 antibody; NG2; myelin
basic protein; immunohistochemistry; neurofilament protein; microglia; periventricular leukomalacia; prematurity
Copyright © 2001 Society for Neuroscience 0270-6474/01/2141302-11$05.00/0
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