We proposed that hypoxic-ischemic injury suffered on postnatal day 1 (
PI) in the newborn rat would yield significant and reproducible brain
injury simulating that seen in a midgestation human brain. The P1 pup
was subjected to ipsilateral common carotid ligation followed by 3.5 h
of 6% O-2 and demonstrated consistent histological changes in the ips
ilateral hemisphere. At P2 neuronal loss and edema were pronounced in
cortex and caudate; edema subsequently declined by P3. Astrocytic and
microglial reactivity were seen as early as 24 h after injury, and by
P10 both were extensive in damaged areas. There was marked loss of whi
te matter on the affected side. We have demonstrated a reproducible mo
del of hypoxic-ischemic injury to the very immature brain that can be
used to elucidate mechanisms of neuronal loss and periventricular leuk
omalacia.