title: A putative role for homocysteine in the pathophysiology of acute bacterial meningitis in children.
abstract: BACKGROUND
  Acute bacterial meningitis frequently causes cortical and hippocampal neuron loss leading to permanent neurological sequelae. Neuron death in acute bacterial meningitis involves the excessive activation of NMDA receptors and p53-mediated apoptosis, and the latter is triggered by the depletion of NAD + and ATP cellular stores by the DNA repair enzyme poly(ADP-ribose) polymerase. This enzyme is activated during acute bacterial meningitis in response to DNA damage induced, on its turn, by reactive oxygen and nitrogen species. An excess of homocysteine can also induce this cascade of events in hippocampal neurons. The present work aimed at investigating the possible involvement of homocysteine in the pathophysiology of meningitis by comparing its concentrations in cerebrospinal fluid (CSF) samples from children with viral or acute bacterial meningitis, and control individuals.
  
  
  METHODS
  Homocysteine and cysteine concentrations were assessed by high-performance liquid chromatography in CSF samples from nine patients with acute bacterial meningitis, 13 patients with viral meningitis and 18 controls (median age: 4 years-old; range: <1 to 13) collected by lumbar puncture at admission at the Children's Hospital Joao Paulo II - FHEMIG, from January 2010 to November 2011.
  
  
  RESULTS
  We found that homocysteine accumulates up to neurotoxic levels within the central nervous system of patients with acute bacterial meningitis, but not in those with viral meningitis or control individuals. No correlation was found between homocysteine and cysteine concentrations and the cerebrospinal fluid standard cytochemical parameters.
  
  
  CONCLUSIONS
  Our results suggest that HCY is produced intrathecally in response to acute bacterial meningitis and accumulates within the central nervous system reaching potentially neurotoxic levels. This is the first work to propose a role for HCY in the pathophysiology of brain damage associated with acute bacterial meningitis.
authors.affiliation: Biosystems Informatics, Research Center Rene Rachou, FIOCRUZ, Av. Augusto de Lima 1715, Belo Horizonte, MG Zip Code: 30190-002 Brazil.
authors.forename: Roney Santos
authors.initials: RS
authors.lastname: Coimbra
authors.affiliation: Department of Psychobiology, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, SP Brazil.
authors.forename: Bruno Frederico Aguilar
authors.initials: BF
authors.lastname: Calegare
authors.affiliation: Children's Hospital João Paulo II - FHEMIG, Belo Horizonte, MG Brazil.
authors.forename: Talitah Michel Sanchez
authors.initials: TM
authors.lastname: Candiani
authors.affiliation: Department of Psychobiology, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, SP Brazil.
authors.forename: Vânia
authors.initials: V
authors.lastname: D'Almeida
keywords: Acute bacterial meningitis; Homocysteine; Neurotoxicity