This study examines cell death and proliferation in the white matter after
neonatal stroke. In post-natal day 7 injured rat, there was a marked reduction
in myelin basic protein (MBP) immunostaining mainly corresponding to numerous
pyknotic immature oligodendrocytes and TUNEL-positive astrocytes in the
ipsilateral external capsule. In contrast, a substantial restoration of MBP, as
indicated by the MBP ratio of left-toright, occurred in the cingulum at 48
(1.27 +- 0.12) and 72 (1.30 +- 0.18, p<0.05) hours of recovery as compared to
age-matched controls (1.03 +- 0.14). Ki-67 immunostaining revealed a first peak
of newly-generated cells in the dorsolateral hippocampal subventricular zone
and cingulum at 72 hours after reperfusion. Double immunofluorescence revealed
that most of the Ki-67-positive cells were astrocytes at 48 hours and NG2
pre-oligodendrocytes at 72 hours of recovery. Microglia infiltration occurs
over several days in the cingulum and a huge quantity of macrophages reached
the subcortical white matter where they engulfed immature oligodendrocytes. The
overall results suggest that the persistent activation of microglia involves a
chronic component of immunoinflammation, which overwhelms repair processes and
contributes to cystic growth in the developing brain.Comment: 30 page