Changes in iron histochemistry after hypoxic-ischemic brain injury in the neonatal rat.
Iron can contribute to hypoxic-ischemic brain damage by catalyzing the formation of free radicals. The immature brain has high iron levels and limited antioxidant defenses. The objective of this study was to describe the early alterations in nonheme iron histochemistry following a hypoxic-ischemic (HI) insult to the brain of neonatal rats. We induced a HI insult to the right 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 for iron using the intensified Perls stain. Increased iron staining was first detected within the cytoplasm of cells with pyknotic nuclei at 4 hr of recovery. Staining increased rapidly over the first 24 hr in regions of ischemic injury. By 7 days recovery, reactive glia and cortical blood vessels also stained. Increased staining in gray matter persisted at 3 weeks of recovery, whereas white matter tracts had fewer iron-positive cells compared to normal. The early increase in iron staining could be caused by an accumulation of iron posthypoxicischemic injury or a change in iron from nonstainable heme iron to stainable nonheme iron. Regardless of the source, our results indicate that there is an increase in iron available to promote oxidant stress in the neonatal rat brain following hypoxia-ischemia.
Palmer
C
C
Department of Pediatrics, Pennsylvania State University School of Medicine, Milton S. Hershey Medical Center, Hershey 17033-0850, USA.
Menzies
S L
SL
Roberts
R L
RL
Pavlick
G
G
Connor
J R
JR
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D006651:Histocytochemistry; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000473:pathology; D007501:Iron / Q000032:analysis / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D013997:Time Factors
D007501:Iron