Cerebrovascular damage in young rabbits after intravenous administration of Shiga toxin 2

Acute encephalopathy associated with Shiga toxin-producing Escherichia coli (STEC) primarily affects children. To elucidate the age-dependent vulnerab ility of the central nervous system (CNS), we injected Shiga toxin 2 (Stx2) intravenously to young rabbits and examined the clinical and pathological effects on the CNS. Although neurological disorders caused by Stx2 were sim ilar between young and adult rabbits, the dose required to produce them in the young was one third of that required for the adults. Vascular lesions a ppeared as early as 24 h after injection in the young, but not at all in th e adult. Arteriolar changes, such as hydropic swelling of the endothelial c ells and karyorrhexis of the medial cells, were specific to the CNS of youn g animals. Evidence for apoptosis of vascular cells was scarce because DNA strand breaks and activation of caspases-3 and -9 were absent in the vast m ajority. Given our results, we conclude that the cerebral blood vessels of immature brains are more vulnerable to Stx2 than those of adults in the rab bit.