Long-term deficits following cerebral hypoxia-ischemia in four-week-old rats: Correspondence between behavioral, histological, and magnetic resonanceimaging assessments

We examined whether following a hypoxic-ischemic insult in young animals th ere are long-lasting functional deficits that correlate either to histologi cal tissue damage or to potential compensatory plasticity changes. Four-wee k-old rats were subjected to an episode of cerebral hypoxia-ischemia (right carotid artery occlusion + 30 min of hypoxia) or a sham operation. In hypo xic-ischemic animals there were gross neurological deficits 1, 24, and 48 h postinsult with recovery by 1 week. Behavioral deficits were observed in b oth the acquisition and the performance of a response duration differentiat ion test and a fine motor control test (staircase test) 3 months after the hypoxia-ischemia. Functional magnetic resonance imaging studies demonstrate d less activation in the sensory-motor cortex of hypoxic-ischemic animals i n response to left vs right forepaw stimulation 4 months postinsult, Histol ogical assessment delineated striatal, cortical, and hippocampal damage in the hypoxic-ischemic hemisphere and a reduction in cortical thickness, bila terally. GFAP immunoreactivity was increased in injured striatum and cortex . Neurofilament heavy chain (NF200) immunoreactivity was normally most inte nse in white matter and decreased in areas of ipsilateral cortical damage, Synaptophysin immunoreactivity was reduced around areas of infarction and s omewhat increased in adjacent undamaged striatum and in layer IV of parieta l cortex, The histological damage or chronic degenerative changes could acc ount for much of the variance in functional outcome detected with sensitive behavioral tests so that overall the compensatory or plasticity changes ev ident within the juvenile brain are rather modest. (C) 2000 Academic Press.