Detrimental effect of nitric oxide inhibition in experimental bacterial meningitis

Leib, Stepen L.; Kim, Young S.; Black, Stephen M.; Ferriero, Donna M.; Täuber, Martin G.

doi:10.1002/ana.410390422

Cited by 6 publications

(3 citation statements)

References 5 publications

(1 reference statement)

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“…22 To study the pathophysiologic processes after bacterial invasion of the central nervous system (CNS), direct intracerebroventricular or intracisternal injections of the pathogen is used and results in the development of meningitis in nearly 100% of inoculated animals. The successful establishment of experimental models of meningitis due to GBS, 17,23,24 L monocytogenes, [25][26][27] S pneumoniae, 28,29 H influenzae, 30 and E coli; 31 as well as, to a limited extent, N meningitis [32][33][34] has been reported. Based on the current knowledge on the pathophysiology of BM, the authors arbitrarily divided the processes leading to BM into three steps of the disease progression to more easily group them into mechanistic entities: colonization and invasion of the CNS; bacterial multiplication and CNS inflammation; and development of brain damage (Fig.…”

Section: Pathophysiology Of Bmmentioning

confidence: 99%

Meningitis in Neonates: Bench to Bedside

Grandgirard

Leib

2010

Clinics in Perinatology

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Section: Pathophysiology Of Bmmentioning

confidence: 99%

Meningitis in Neonates: Bench to Bedside

Grandgirard

Leib

2010

Clinics in Perinatology

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“…These fatal interactions apparently involve aspects of bacterial species and the specificity and selectivity of the arginine substrate inhibitor. For example, where experiments were performed during which NO production was competitively inhibited with the administration of nonmetabolizable arginine substrate analogs, experimental infection with a pathogen resulted in the inability for the defending immune cells to mount the needed NO response to kill the pathogens (Chan et al, 1995;Leib et al, 1996). Thus, stringent checks and balances need to be in place to coordinate and stabilize these biochemical events and it appears that AM performs such a coordinating function.…”

Section: Defining Inflammationmentioning

confidence: 99%

Adrenomedullin has multiple roles in disease stress: Development and remission of the inflammatory response

Elsasser

Kahl

2002

Microscopy Res & Technique

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The upregulation of adrenomedullin (AM) gene expression and increases in systemic circulatory as well as localized tissue AM concentrations is well coordinated with the onset and progression of trauma, infection, and sepsis. As such, the coordinated change in AM suggests a key role for this peptide in the inflammatory response. By clinical definition, the process of inflammation constitutes an orchestrated cascade of localized tissue and systemic responses to immunological challenges. Classical responses to the onset of disease stresses are manifested in the timely elaboration of humoral, blood-borne signal effectors (such as adrenocortical and locally produced tissue hormones, immune cytokines, and inorganic signals such as nitric oxide) as well as patterned migration and infiltration of circulating bone marrow-derived cells (mononuclear cells such as monocyte-macrophages and polymorphonuclear cells like neutrophils) largely associated with or delivered through the vascular system. The body's attempts to combat acute infection to restore homeostatic equilibrium are further compromised by underlying disease situations. Atherosclerosis, diabetes, and cardiovascular disease, as well as nutritional metabolic derangements and persistent subclinical infection perturb the regulatory feedback loops necessary for proper control of response effectors like hormones and cytokines. When imbalances occur, tissue necrosis can ensue as driven by free radical damage to cell components. A true appreciation of the inflammatory response can only be grasped through an integrative approach in which the relationship between the different physiological systems is viewed in terms of a changing, dynamic interaction. In essence, the inflammatory response can be thought of in three phases: a period of severity assessment, a period of remediation, and a period of homeostatic restoration. Indeed, AM has differential effects on cellular metabolism, immune function, endocrine function, and cardiovascular function. This peptide appears to play a pivotal role in both reprioritizing the biological needs of tissues and organs during the three phases of inflammatory response as well as a role in restoring homeostatic equilibrium to the body.

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“…However, increased mortality has also been reported after administration of NOS inhibitors to rats with experimental meningitis [8,10]. In an infant rat model of group B streptococcal meningitis, administration of the inducible NOS inhibitor aminoguanidine resulted in increased neuronal injury [11], higher bacterial titers and worsening of cerebral ischemia [12]. Therefore, the available data on the role of NO and the efficacy of NOS inhibitors as an adjunctive therapy in bacterial meningitis are still controversial, and further studies will be necessary to clarify this.…”

Section: Introductionmentioning

confidence: 99%

7-Nitroindazole, but Not Aminoguanidine, Attenuates the Acute Inflammatory Responses and Brain Injury during the Early Phase of <i>Escherichia coli</i> Meningitis in the Newborn Piglet

2001

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We evaluated the anti-inflammatory and neuroprotective effects of the selective neuronal nitric oxide synthase inhibitor 7-nitroindazole and aminoguanidine, which predominantly inhibits inducible nitric oxide synthase, during the early phase of experimental bacterial meningitis in the newborn piglet. Meningitis was induced by intracisternal injection of 10⁸ colony-forming units of Escherichia coli in 100 µl of saline. 7-Nitroindazole significantly attenuated the meningitis-induced acute inflammatory responses such as increased intracranial pressure, decreased cerebrospinal fluid (CSF) glucose concentration, and CSF leukocytosis at 2 h. However, meningitis-induced CSF leukocytosis at 4 h and increased CSF lactate and tumor necrosis factor alpha levels were not significantly attenuated. Reduced cerebral cortical cell membrane Na⁺,K⁺-ATPase activity and increased lipid peroxidation products, indicative of meningitis-induced brain cell membrane dysfunction, were also significantly improved with 7-nitroindazole treatment. In contrast, although aminoguanidine significantly attenuated the increase in the CSF tumor necrosis factor alpha level, it failed to attenuate the acute inflammation and the ensuing brain injury in bacterial meningitis. In summary, 7-nitroindazole, but not aminoguanidine, significantly attenuated the acute inflammatory responses and brain injury during the early phase of neonatal bacterial meningitis.

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Detrimental effect of nitric oxide inhibition in experimental bacterial meningitis

Cited by 6 publications

References 5 publications

Meningitis in Neonates: Bench to Bedside

Meningitis in Neonates: Bench to Bedside

Adrenomedullin has multiple roles in disease stress: Development and remission of the inflammatory response

7-Nitroindazole, but Not Aminoguanidine, Attenuates the Acute Inflammatory Responses and Brain Injury during the Early Phase of <i>Escherichia coli</i> Meningitis in the Newborn Piglet

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