1997 Abstracts The American Pediatric Society and The Society for Pediatric Research

Pediatric Research (1997) 41, 182–182; doi:10.1203/00006450-199704001-01098

Post hypoxic-ischemic (HI) hypothermia gives long term functional and neuropathological protection in female neonatal rats but not in males. • 1079

Marianne Thoresen1, Elsa Bona1, Else Loeberg1, Ralph Baagenholm1 and Henrik Hagberg1

1Pediatr, Ullevaal Hosp, Oslo, Norway, Anat, Univ of Gothenburg, Goth, Sweden, Path, Ullevaal Hosp, Oslo, Norway, Physiol, Univ of Goth, Goth, Sweden, Obs, Sahlgrenska Hosp, Goth, Sweden

(Spon by: Andrew Whitelaw)

Introduction: Hypothermia (HT) applied after HI has shown neuroprotecton after 1 week of survival in both adult and neonatal animal models. In adult models post-HI hypothermic protection have been inconsistent after longer survival.Our randomised study of post-HI HT examined pathology and functional ability in neonatal rats of both sexes after 1 or 6weeks.Methods: On postnatal day seven (P7) 106 rat pups of both sexes had their left carotid artery ligated, followed by 70 min hypoxia (n=94)(7.70% O2 in N2) at 36°C Tair (Trectal37°C). The pups were then randomized to 6h HT (target Trectal 32°C) or normothermia (NT) (Trectal 37°C) in separate chambers before returning to the dam for 1(n=32) or 6(n=62) weeks survival. Brain sections were stained with H&E and examined for morphological changes in cortex, hippocampus, basal ganglia (BG) and thalamus on a 9 step scale at five coronal levels. At P42 and P49 61 animals and 20 controls (CT) were sensorimotor tested with postural reflex/ limb placing, foot-fault, swing and paw-preference test with results pooled as a functional total rank for each animal. Results: At one week survival HT reduced the neuropathological damage in both male and female rats by 25% (thalamus), 27% (cortex), 28% (BG) and 43% (hippocampus) as compared to NT. After 6 weeks survival a significant reduction of the brain lesion of HT vs NT animals was seen only in the female HT rats by 57% (thalamus), 40%(cortex), 59% (BG) and 54% (hippocampus) as compared to female NT rats. Total functional rank correlated well with neuropathological outcome in female(r=0.77) rats an differed between NT (100±34) and HT(150±35)rats. Conclusion: Posthypoxic HT is neuroprotective in neonatal rats of both sexes after 1 weeks survival. After 6 weeks only female rats show protection from HT, possibly due to hormonal influence on neuronal injury.