Blood-brain barrier permeability in staphylococcal cerebritis and early brain abscess

Abstract

The pattern of radiographic enhancement in cases of brain abscess has been extensively studied, but the magnitude of blood-brain barrier (BBB) damage that accompanies enhancement has not. The question of whether BBB permeability increases continuously as a cerebritis evolves into an abscess was studied. The tracers 3H-labeled aminoisobutyric acid and 14C-labeled butanol were used in a rat Staphylococcus aureus cerebritis model to measure simultaneously BBB permeability and blood flow. The rats were examined at 1, 2, 3, 5, or 7 days after inoculation, and tissue samples were collected from the cerebritis site and uninoculated regions. Permeability of the BBB in the cerebritis region increased to five times the normal values by 72 hours after inoculation, then reached a plateau. The plasma volume in the cerebritis region increased to six times greater than the normal value at 72 hours, then remained unchanged. Uninoculated brain in both ipsilateral and contralateral hemispheres showed no significant changes. Cerebral blood flow was not substantially altered at the inoculated or uninoculated sites. In this model, incidence of BBB damage rises rapidly, reaches a plateau, and does not continue to increase despite the ongoing evolution of a cerebritis into an abscess. The BBB damage is accompanied by an increase in the regional plasma volume, a novel finding that has not been previously reported in central nervous system inflammation. These results suggest that the vascular events contributing to brain edema formation become established early in the cerebritis phase and imply that control of the host's inflammatory response is important in the management of cerebritis-associated brain edema.

MyD88-Dependent Signals Are Essential for the Host Immune Response in Experimental Brain Abscess

“…In contrast, vasogenic edema occurs because of brain-blood barrier compromise, resulting in extracellular fluid accumulation. Both forms of cerebral edema can contribute to an increase in intracranial pressure; however, vasogenic edema is thought to represent the predominant response observed in brain abscess (2,3). This pathogenic fluid dynamic in the CNS is likely one causative agent for the ensuing tissue necrosis observed in brain abscesses through the physical compression of cerebral vasculature and subsequent ischemia.…”

“…Currently, we do not have a good understanding of the pathological mechanisms that dictate whether animals succumb to infection during brain abscess development. However, interpretation of available studies suggests a multifactorial etiology in which both elevated cerebral edema and necrosis play a role (2,3,6). Cerebral edema is generally divided into two types, vasogenic and cytotoxic, depending on the mechanism of edema formation (52).…”

“…Brain abscesses are typified by extensive edema and tissue necrosis and tend to localize at white-gray matter junctions where microcirculatory flow is poor (2,3). In addition to the sequential progression from cerebritis to necrosis during brain abscess evolution, the activation of resident glial cells and influx of peripheral leukocytes demonstrate temporal patterns (1).…”

“…A pivotal component of innate immunity is the intracellular protein MyD88, which represents the central adapter protein for the majority of the TLRs (1) identified to date (with the exception of TLR3) in addition to transducing activation signals emanating from the IL-1 and IL-18 receptors (14 -16). Previous studies have demonstrated that MyD88 knockout (KO) 3 mice exhibit dramatic defects in antibacterial immunity in a variety of infectious disease models, highlighting the importance of this adapter in influencing a wide array of host responses (17)(18)(19)(20)(21).…”

Concepts and Mechanisms: Crossing Host Barriers

“…These data suggest a role for bacterial factors, like cell wall components and toxins, in promoting BBB permeability either directly or indirectly through induction of host factors. Several reports have linked increased BBB permeability to a parallel increase in levels of circulating cytokines in the blood and CSF during infection (Lo et al 1994). Tumor necrosis factor a (TNFa), IL-1, and IL-6 are major early response cytokines that trigger a cascade of inflammatory mediators, including other cytokines, chemokines, arachidonic acid metabolites, and reactive nitrogen and oxygen intermediates (Dinarello 2000).…”