NEURONAL AND VASCULAR PATHOLOGY PRODUCED BY VEROCYTOTOXIN-2 IN THE RABBIT CENTRAL-NERVOUS-SYSTEM

To study the pathogenesis of the central nervous system (CNS) involvem ent associated with verocytotoxin-producing Escherichia coli infection , we developed an animal model by administering verocytotoxin 2 to rab bits either intravenously or intrathecally. After an interval of 2-9 d ays, the rabbits became paralyzed in a dose-dependent manner and in th e absence of renal impairment. The minimal intravenous and intrathecal doses that produced these neurological signs were 250 and 0.4 ng/kg, respectively. After intravenous administration, most of the toxin was cleared from the serum within 24 h, with concomitant transition of a s mall amount into the cerebrospinal fluid. Pathological examination rev ealed that neurons in various CNS regions showed atrophy, cytoplasmic hyperchromasia and nuclear pyknosis as early as 6 h after administrati on. The distribution of affected neurons was constant and irrespective of the route of administration. Abnormalities of the blood vessels, s uch as the thickening of arterioles walls, were noted from 2 days afte r administration. The vascular lesions became more prominent after the intrathecal injection, which caused thrombosis and multiple infarctio n. Selective deposition of the toxin on the vessel walls was demonstra ted immunohistochemically. Thus, the pathological manifestations of ve rocytotoxin 2 neurotoxicity consisted essentially of two types of lesi ons, early neuronal and late vascular, both of which might have develo ped under the influence of the toxin that had entered the CNS by cross ing or circumventing the blood-brain barrier.