Influence of Escherichia coli shiga toxin on the mammalian central nervous system

In severe cases of the infectious disease by Shiga toxin-producing Escherichia coli (STEC), patients display renal dysfunction known as hemolytic uremic syndrome (HUS) and central nervous system (CNS) failure. Among those severe symptoms, patients with CNS dysfunction with HUS have a greater chance of getting severe sequelae and mortality than with HUS alone. Autopsy of the CNS shows mostly edema and hypoxic-ischemic changes, often with microhemorrhages. Magnetic resonance imaging (MRI) of brains of patients confirms hemorrhagic component involvement. This suggests the weakening of the blood-brain barrier (BBB) during the disease. Also, cerebrospinal fluid (CSF) analysis shows the weakening of the blood-CSF barrier. Although evidence of vascular involvement in CNS exists, the typical observation of microthrombosis in renal pathology is often absent in CNS. Importantly, there are people who develop CNS symptoms before the onset of HUS. This suggests direct involvement of Shiga toxin (Stx) in CNS disease which is in addition to renal involvement. The advantages of animal models are that Stx receptor expression in normal CNS tissue can be determined, and changes in histopathology, hematology, and serum and CSF contents can be analyzed at several different time points, which allow investigation of the nature of the disease. Importantly, in animal models with either STEC oral inoculation or purified Stx injection, paralysis of extremities is commonly observed. This shows the central role of Stx in CNS dysfunction in this disease. It is anticipated that precise mechanisms of Stx influence in the CNS will be delineated, and this information will lead to effective therapeutics in the near future.