Pathophysiology of Bacterial Infection of the Central Nervous System and its Putative Role in the Pathogenesis of Behavioral Changes

Abstract

Invasion of the central nervous system (CNS) by microorganisms is a severe and frequently fatal event during the course of many infectious diseases. It may lead to deafness, blindness, cerebral palsy, hydrocephalus, cognitive impairment or permanent neurological dysfunction in survivors. Pathogens can cross the blood-brain barrier by transcellular migration, paracellular migration and in infected macrophages. Pathogens may breach the blood-brain barrier and be recognized by antigen-presenting cells through the binding of Toll-like receptors. This induces the activation of nuclear factor kappa B or mitogen-activated protein kinase pathways and subsequently induces leukocyte infiltration and proliferation and the expression of numerous proteins involved in inflammation and the immune response. Many brain cells can produce cytokines, chemokines and other pro-inflammatory molecules in response to bacteria stimuli; as a consequence, polymorphonuclear cells are attracted and activated, and release large amounts of superoxide anion and nitric oxide, leading to peroxynitrite formation and oxidative stress. This cascade leads to lipid peroxidation, mitochondrial damage and blood-brain barrier breakdown, contributing to cellular injury during neuronal infection. Current evidence suggests that bacterial CNS infections can play a role in the etiopathogenesis of behavioral disorders by increasing pro-inflammatory cytokines and bacterial virulence factors. The aim of this review is to summarize the current knowledge of the relevant pathophysiologic steps in CNS infections.

Adverse childhood experiences influence the detrimental effect of bipolar disorder and schizophrenia on cortico-limbic grey matter volumes

“…Neuroinflammation has been reported in patients with psychiatric disorders (Najjar et al, 2013), and is typically associated with microglial activation. A chronic activation of the immune system by microglia would produce cytokines that will render the brain vulnerable and unstable thus leading to mood disturbances (Schroeter et al, 2011) and to behavioural and cognitive deficits (Barichello et al, 2013;Hu et al, 2014). Indeed, increased markers of excitotoxicity and neuroinflammation have been reported in postmortem frontal cortex of both BD (Rao et al, 2010) and SCZ patients (Bayer et al, 1999;Radewicz et al, 2000).…”

Ventricular shunt infections: Immunopathogenesis and clinical management

“…Chronic inflammation has been associated with neurodegeneration, behavioral disorders, seizures, and cognitive impairment (Barichello et al 2013, Zhao et al 2013, Hagberg, Gressens & Mallard 2012). Of particular relevance to the neonates and infants who are at highest risk of SI, the effect of CNS inflammation in the perinatal period on long term outcomes has been repeatedly noted in neonatal animal infection models (Kosmac et al 2013, Meyer, Feldon & Fatemi 2009, Nelson, Willoughby 2000, Chen et al 2011, Bilbo, Schwarz 2009).…”

Sodium Butyrate Prevents Memory Impairment by Re-establishing BDNF and GDNF Expression in Experimental Pneumococcal Meningitis

“…Therefore, our knowledge of the pathophysiology of bacterial meningitis is commonly acquired through patient observation and experimental models that reproduce the same sequelae found in patients. Previously, we demonstrated that animals surviving pneumococcal meningitis presented learning and memory impairments [4,5] and that there was a correlation between a decrease in brain-derived neurotropic factor (BDNF) expression in the hippocampus and memory deficiency [6]. The administration of exogenous BDNF had neuroprotective effects on both the cerebral cortex and hippocampus, increasing the neuronal population and re-establishing normal BDNF and tyrosine-related kinase B (TRKB) levels, which had decreased in the brain during experimental pneumococcal meningitis [7].…”