title: Mechanisms of injury in bacterial meningitis.
abstract: OBJECTIVE
  This review describes the pathophysiology of cellular and axonal injury in bacterial meningitis.
  
  
  RESULTS
  Toll-like receptors have been recognized as important mediators for the initiation of the immune response within the central nervous system. Activation of microglial cells by bacterial products through these receptors increases their ability to phagocytose bacteria, but can also lead to destruction of neurons. The cholesterol-binding hemolysin pneumolysin has a direct toxic effect on neuronal cells. Adjuvant therapy with corticosteroids and glycerol improved the outcome of bacterial meningitis in clinical studies.
  
  
  CONCLUSIONS
  Brain damage in bacterial meningitis leading to long-term neurologic sequelae and death is caused by several mechanisms. Bacterial invasion and the release of bacterial compounds promote inflammation, invasion of leukocytes and stimulation of microglia. Leukocytes, macrophages and microglia release free radicals, proteases, cytokines and excitatory amino acids, finally leading to energy failure and cell death. Vasculitis, focal ischemia and brain edema subsequent to an increase in cerebrospinal fluid outflow resistance, breakdown of the blood-brain barrier and swelling of necrotic cells cause secondary brain damage.
authors.affiliation: Department of Neurology, RWTH University Hospital, Aachen, Germany. jgerber@ukaachen.de
authors.forename: Joachim
authors.initials: J
authors.lastname: Gerber
authors.forename: Roland
authors.initials: R
authors.lastname: Nau
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D001921:Brain / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology*; D001929:Brain Edema / Q000378:metabolism / Q000503:physiopathology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016920:Meningitis, Bacterial / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D009410:Nerve Degeneration / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology*; D013301:Streptolysins / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D000305:Adrenal Cortex Hormones; D001426:Bacterial Proteins; D018836:Inflammation Mediators; D013301:Streptolysins; D051193:Toll-Like Receptors; C032290:plY protein, Streptococcus pneumoniae