Changes in iron histochemistry after hypoxic-ischemic brain injury in the neonatal rat

Iron can contribute to hypoxic-ischemic brain damage by catalyzing the form ation of free radicals, The immature brain has high iron levels and limited antioxidant defenses. The objective of this study was to describe the earl y alterations in nonheme iron histochemistry following a hypoxic-ischemic ( HI) insult to the brain of neonatal rats, We induced a HI insult to the rig ht cerebral hemisphere in groups of 7-day-old rats. Rats were anesthetized, then their brains were perfused and fixed at 0, 1, 4, 8, 24 hr, and 1, 2, and 3 weeks of recovery, Forty-micron-thick frozen sections were stained fo r iron using the intensified Perls stain. Increased iron staining was first detected within the cytoplasm of cells with pyknotic nuclei at 4 hr of rec overy. Staining increased rapidly over the first 24 hr in regions of ischem ic injury. By 7 days recovery, reactive glia and cortical blood vessels als o stained. Increased staining in gray matter persisted at 3 weeks of recove ry, whereas white matter tracts had fewer iron-positive cells compared to n ormal. The early increase in iron staining could be caused by an accumulati on of iron posthypoxic-ischemic injury or a change in iron from nonstainabl e heme iron to stainable nonheme iron, Regardless of the source, our result s indicate that there is an increase in iron available to promote oxidant s tress in the neonatal rat brain following hypoxia-ischemia. J, Neurosci, Re s. 56:60-71, 1999, (C) 1999 Wiley-Liss, Inc.