Methylprednisolone attenuates inflammation, increase of brain water content and intracranial pressure, but does not influence cerebral blood flow changes in experimental pneumococcal meningitis

Koedel, Uwe; Pfister, Hans‐Walter; Tomasz, Alexander

doi:10.1016/0006-8993(94)90342-5

Cited by 17 publications

(5 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Streptococci possess a teichoic acid containing cell walls capable of inducing meningeal inflammation (Tuomanen et al, 1985) and microvascular changes (Pfister et al, 1992) in experimental pneumococcal meningitis. Cerebral blood flow changes in experimental meningitis can be reversed by dexamethasone (Koedel et al, 1994) or NOS inhibitors; however, a high mortality in the L-NAME treatment group was observed (Haberl et al, 1994). Our results point to a more efficient inhibition of iNOS by dexamethasone compared to L-NA (transcriptional vs. protein level).…”

Section: Discussionmentioning

confidence: 55%

Pneumococcal cell wall components induce nitric oxide synthase and TNF-α in astroglial-enriched cultures

Freyer

Weih

Weber

et al. 1996

Glia

View full text Add to dashboard Cite

Astroglia and microglia, the most numerous cells in the central nervous system (CNS), have been shown to produce the inducible nitric oxide synthase (iNOS) and tumor necrosis factor‐α (TNF‐α) upon stimulation with the cytokines IFN‐γ, IL‐1β, or bacterial lipopolysaccharides (LPS). However, it is not known whether gram‐positive bacteria like Streptococcus pneumoniae cause astroglial cells to release nitric oxide (NO) and TNF‐α. S. pneumoniae meningitis still has a high incidence and mortality in spite of antibiotic therapy. Cell wall components from S. pneumoniae (pneumococcal cell‐wall components, PCW) and TNF‐α have been shown to cause meningeal inflammation and cerebrovascular changes in experimental meningitis. Addition of PCW to cultured rat astroglial cells increased nitrite in the supernatant significantly after 24 h, from 17 ± 21 to 133 ± 62 nM/μg protein. Nitrite release was dose‐dependent in a range shown to cause meningeal inflammation in vivo and was inhibited by the competitive NO synthase inhibitor NW‐nitro‐L‐arginine (L‐NA 10−4 M) and dexamethasone (10−6 M), with transcriptional and translational inhibition by actinomycin D and cycloheximide, respectively. PCW caused a significant increase in the release of TNF‐α from astroglial cells after 4 h, from 2 ± 3.5 pg/ml to 102 ± 13.5 pg/ml, which was inhibited by dexamethasone (10−6 M). Our results suggest a role for astroglial‐derived NO and TNF‐α as mediators of vascular and inflammatory response in the early phase of experimental pneumococcal meningitis. © 1996 Wiley‐Liss, Inc.

show abstract

Section: Discussionmentioning

confidence: 55%

Pneumococcal cell wall components induce nitric oxide synthase and TNF-α in astroglial-enriched cultures

Freyer

Weih

Weber

et al. 1996

Glia

View full text Add to dashboard Cite

show abstract

“…During recent years, a variety of pharmacologic agents that interfere with NF-kB activation in cell culture experiments and in vivo models have been tested in experimental bacterial meningitis, including glucocorticoids, aspirin, antibodies to TNFa, IL-1b, and IL-10, and antioxidants [6,7,10,42,[62][63][64][65]. For example, administration of dexamethasone completely reversed the development of brain edema, the increase in CSF lactate level, and CSF pressure in experimental pneumococcal meningitis in rabbits [62].…”

Section: Discussionmentioning

confidence: 98%

Pharmacologic Interference with NF‐κB Activation Attenuates Central Nervous System Complications in Experimental Pneumococcal Meningitis

et al. 2000

View full text Add to dashboard Cite

This study assessed the effects of 2 different inhibitors of NF-kappaB activation on central nervous system complications and clinical symptoms in an advanced stage of experimental pneumococcal meningitis: the calpain inhibitor I N-acetyl-leucinyl-leucinyl-norleucinal (ALLN), which interferes with IkappaB proteolysis, and BAY 11-7085, which inhibits IkappaB phosphorylation. Pneumococcal meningitis was associated with an increase in NF-kappaB activity, as determined by immunohistochemistry and Western blot analysis of rat brains 24 h after infection. Treatment with ALLN or BAY 11-7085 improved the clinical scores of infected rats, compared with those of untreated infected rats. This beneficial effect was parallelled by a significant reduction of the increase in intracranial pressure, blood-brain barrier permeability (as measured by the Evans blue-extravasation technique), cerebrospinal fluid (CSF) pleocytosis, CSF interleukin-6 levels, and impairment of cerebrovascular CO(2) reactivity and autoregulation. Thus, pharmacologic interference with NF-kappaB activation might be a possible target for adjunctive therapy in bacterial meningitis.

show abstract

“…Furthermore, dexamethasone decreased ICP, brain edema, and CSF pleocytosis in rats with PCW-induced meningeal inflammation (255,388). In a rabbit model, neuron-specific enolase, a marker of overall neuronal damage, was reduced in animals treated with ceftriaxone and dexamethasone compared to those treated with ceftriaxone alone, though an increase in hippocampal apoptosis was also observed (556).…”

Section: Adjunctive Dexamethasone Therapymentioning

confidence: 92%

Pathogenesis and Pathophysiology of Pneumococcal Meningitis

et al. 2011

View full text Add to dashboard Cite

SUMMARY Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae , which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy.

show abstract

Methylprednisolone attenuates inflammation, increase of brain water content and intracranial pressure, but does not influence cerebral blood flow changes in experimental pneumococcal meningitis

Cited by 17 publications

References 41 publications

Pneumococcal cell wall components induce nitric oxide synthase and TNF-α in astroglial-enriched cultures

Pneumococcal cell wall components induce nitric oxide synthase and TNF-α in astroglial-enriched cultures

Pharmacologic Interference with NF‐κB Activation Attenuates Central Nervous System Complications in Experimental Pneumococcal Meningitis

Pathogenesis and Pathophysiology of Pneumococcal Meningitis

Contact Info

Product

Resources

About