Pathophysiology of neonatal acute bacterial meningitis

Abstract

Neonatal meningitis is a severe acute infectious disease of the central nervous system and an important cause of morbidity and mortality worldwide. The inflammatory reaction involves the meninges, the subarachnoid space and the brain parenchymal vessels and contributes to neuronal injury. Neonatal meningitis leads to deafness, blindness, cerebral palsy, seizures, hydrocephalus or cognitive impairment in approximately 25–50 % of survivors. Bacterial pathogens can reach the blood–brain barrier and be recognized by antigen-presenting cells through the binding of Toll-like receptors. They induce the activation of NFκB or mitogen-activated protein kinase pathways and subsequently upregulate leukocyte populations and express numerous proteins involved in inflammation and the immune response. Many brain cells can produce cytokines, chemokines and other pro-inflammatory molecules in response to bacterial stimuli, and polymorphonuclear leukocytes are attracted, activated and released in large amounts of superoxide anion and nitric oxide, leading to peroxynitrite formation and generating oxidative stress. This cascade leads to lipid peroxidation, mitochondrial damage and breakdown of the blood–brain barrier, thus contributing to cell injury during neonatal meningitis. This review summarizes information on the pathophysiology and adjuvant treatment of acute bacterial meningitis in neonates.