Background and Purpose-In premature infants, many of whom experience ischem
ic brain insults, the environment of rearing influences cognitive outcome.
We developed a model to evaluate the effect of rearing conditions on learni
ng after unilateral cerebral hypoxia-ischemia (HI) in 7-day-old (P7) rats.
We hypothesized that neonatal handling would benefit rats recovering from a
n episode of HI.
Methods-Seventeen litters of P7 Long-Evans rats underwent either HI (right
carotid ligation followed by 1.5 hours in 8% O-2) or control procedures. Fr
om P8 to P14, randomized litters were either handled (15 minutes of separat
ion from dam per day) or nonhandled. After P55, learning was tested in the
Morris water maze. To evaluate injury severity, hippocampal, cortical, and
striatal volumes were measured.
Results-In water-maze performance, ANCOVA revealed an interaction between h
andling and severity of hippocampal damage. Among HI rats, handled rats lea
rned faster when hippocampal damage was moderate (P < 0.01, repeated-measur
es ANOVA), with no benefit when damage was mild or severe.
Conclusions-These observations suggest the beneficial cognitive effect of n
eonatal handling was limited to animals with moderate damage. Neonatal hand
ling in post-HI rats may be a useful model in which to study mechanisms und
erlying the benefits of post-HI developmental intervention.