University of Virginia Health System

The main focus of the Scheld research laboratory is on the pathogenesis and pathophysiology of infections of the central nervous system (CNS), particularly meningitis. These studies explore the complex bacterial/host relationship responsible for alterations in critical homeostatic mechanisms of the CNS including neuronal injury and death, altered permeability of the blood-brain barrier (BBB) at the level of the cerebromicrovascular endothelium, and induction of subarachnoid space inflammation. Bacterial cell surface constituents including capsule, cell wall, outer membrane vesicles, and lipopolysaccharide have been the focus of previous experiments. Current studies are focusing on the role of reactive oxygen and nitrogen intermediates (particularly nitric oxide and its metabolites) in altered CNS homeostasis. The studies utilize cerebromicrovascular ndothelial cells in tissue culture as well as animal models of meningitis to elucidate the mechanisms responsible for CNS injury. Current experiments examine leukocyte-endothelial interactions at the level of the blood-brain barrier with an emphasis on ICAM-1, the correlation of cerebrospinal fluid (CSF) nitrite concentrations (a metabolite of nitric oxide) with altered CNS homeostasis, detection of upregulation of inducible nitric oxide synthase in situ including molecular techniques for the detection of messenger RNA, and interventions designed to reduce subarachnoid space inflammation and improve the neurologic outcome from this infection.