Pathophysiology of bacterial meningitis: mechanism(s) of neuronal injury.
No bacterial disease has undergone a more dramatic change in epidemiology during the past decade than acute bacterial meningitis. This review describes the changing epidemiology and considers some important recent observations that contribute to our understanding of the pathogenesis and pathophysiology of meningitis. The major focus is on the mechanisms of neuronal injury and the pathophysiologic concepts responsible for death and neurologic sequelae. In recent years, experimental studies have amplified our understanding of the substantial body of evidence that now implicates cytokines and chemokines, proteolytic enzymes, and oxidants in the inflammatory cascade leading to tissue destruction in bacterial meningitis. The molecular mechanisms responsible for oxidant-induced neuronal injury in meningitis are explored in some depth. Genetic targeting and/or pharmacologic blockade of the implicated pathways may be a future strategy for therapeutic adjunctive measures to improve outcome and may hold substantial promise, in concert with antimicrobial agents, in humans with acute bacterial meningitis.
Scheld
W Michael
WM
Division of Infectious Diseases, Department of Internal Medicine, University of Virginia School of Medicine, PO Box 801342, Charlottesville, VA 22908, USA. wms@virginia.edu
Koedel
Uwe
U
Nathan
Barnett
B
Pfister
Hans-Walter
HW
D000293:Adolescent; D000328:Adult; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D016920:Meningitis, Bacterial / Q000453:epidemiology / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology*; D008586:Meningitis, Pneumococcal / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D051379:Mice; D009474:Neurons / Q000382:microbiology / Q000473:pathology*; D051381:Rats; D013296:Streptococcus pneumoniae / Q000276:immunology
D000893:Anti-Inflammatory Agents; D016207:Cytokines