Cerebral blood flow response to a hypoxic-ischemic insult differs in neonatal and juvenile rats

Abstract

To compare the cerebral blood flow (CBF) response to a transient episode of hypoxia–ischemia producing damage in neonatal and juvenile rats. One- and four-week-old rats were subjected to unilateral carotid artery occlusion plus hypoxia (8% oxygen). Perfusion MR images were acquired either in sham controls or in hypoxic–ischemic rats before, during, 1 h and 24 h after hypoxia–ischemia. At 24 h post hypoxia–ischemia, T ₂ maps and histology were used to assess damage. In sham controls, CBF increased twofold between the age of one and four weeks. Reductions in CBF ipsilateral to the occlusion occurred during hypoxia–ischemia followed by a substantial recovery at 1 h post in both age groups. However, contralaterally, hyperemia occurred during hypoxia–ischemia in four-week but not one-week-old rats. Similarly, hyperemia occurred ipsilaterally at 24 h post hypoxia–ischemia in four-week but not one-week-olds, corresponding to the distribution of elevations in T _2. Despite CBF differences, extensive cell death occurred ipsilaterally in both age groups. The CBF responses to hypoxia–ischemia and reperfusion differ depending on postnatal age, with hyperemia occurring in juvenile but not neonatal rats. The results suggest a greater CBF responsiveness and differential relationship between post-ischemic vascular perfusion and tissue injury in older compared with immature animals.