TNF is a key mediator of septic encephalopathy acting through its receptor, TNF receptor-1☆
Section snippets
Animals
Mice with targeted deletion of TNFR1 (TNFR1−/−) were obtained from The Jackson Laboratory (Bar Harbor, ME) and used for experiments at 8 weeks of age. Because these mice are on a C57BL/6 background, age-matched C57BL/6 mice were used as controls. The animals were maintained with 12 h light and dark cycles with free access to food and water. One group was given LPS (from Escherichia coli, serotype 055:B55, Sigma–Aldrich, St. Louis, MO., Lot # 127H4097) as a single injection of 0.15 mg i.p. and
TNF-α mediates septic encephalopathy by acting on its receptor, TNFR1 in brain
TNF-α is released systemically into circulation after LPS administration (Fig. 1). TNF-α could mediate LPS-induced septic encephalopathy, either indirectly by stimulating the release of other proinflammatory cytokines or by acting directly on its receptor, TNFR1 in brain (Schafers et al., 2002, Merrill and Benveniste, 1996). Therefore, to determine the role of TNF-α and its receptor, TNFR1 as mediators in septic encephalopathy, it was important to know whether their expression was altered in
Discussion
Encephalopathy is a common feature in sepsis occurring in ∼25% of patients often before failure of other organ systems. Patients with septic encephalopathy have a higher mortality rate compared to those without brain involvement, likely reflecting the severity of disease and the direct adverse effects of brain involvement. Given the complexity of sepsis, pathogenesis of septic encephalopathy is multifactorial and includes circulatory and metabolic derangements (Papadopoulos et al., 2000),
References (58)
- et al.
Administration of the soluble complement inhibitor, Crry-Ig, reduces inflammation and aquaporin 4 expression in lupus cerebritis
Biochim. Biophys. Acta
(2003) - et al.
Resveratrol inhibits nitric oxide and TNF-alpha production by lipopolysaccharide-activated microglia
Int. Immunopharmacol.
(2005) - et al.
Differential expression, cytokine modulation, and specific functions of type-1 and type-2 tumor necrosis factor receptors in rat glia
J. Neuroimmunol.
(1997) - et al.
Astrocytic response to injury
Prog. Brain Res.
(1992) - et al.
TNFR1-dependent VCAM-1 expression by astrocytes exposes the CNS to destructive inflammation
J. Neuroimmunol.
(2004) - et al.
Blood–brain barrier disruption by stromelysin-1 facilitates neutrophil infiltration in neuroinflammation
Neurobiol. Dis.
(2006) - et al.
Nitric oxide as a retrograde messenger during long-term potentiation in hippocampus
Nitric Oxide Brain Dev. Plast. Dis.
(1998) - et al.
Interleukin-1, nitric oxide and reactive astrocytes
Brain Behav. Immun.
(1995) - et al.
Cytokines in inflammatory brain lesions: helpful and harmful
Trends Neurosci.
(1996) - et al.
Effects of circulating tumor necrosis factor on the neuronal activity and expression of the genes encoding the tumor necrosis factor receptors (p55 and p75) in the rat brain: a view from the blood–brain barrier
Neuroscience
(1999)
Blood–brain barrier permeability to ebiratide and TNF in acute spinal cord injury
Exp. Neurol.
Differential upregulation of aquaporin-4 mRNA expression in reactive astrocytes after brain injury: potential role in brain edema
Neurobiol. Dis.
ICAM-1 regulates neutrophil adhesion and transcellular migration of TNF-alpha-activated vascular endothelium under flow
Blood
Delayed expressed TNFR1 co-localize with ICAM-1 in astrocyte in mice brain after transient focal ischemia
Neurosci. Lett.
Complement-dependent apoptosis and inflammatory gene changes in murine lupus cerebritis
J. Immunol.
Absence of functional alternative complement pathway alleviates lupus cerebritis
Eur. J. Immunol.
Cytokines and acute neurodegeneration
Nat. Rev. Neurosci.
Activation of p55 tumor necrosis factor-alpha receptor-1 coupled to tumor necrosis factor receptor-associated factor 2 stimulates intercellular adhesion molecule-1 expression by modulating a thapsigargin-sensitive pathway in human tracheal smooth muscle cells
Mol. Pharmacol.
Astrocytic-inducible nitric oxide synthase in the ischemic developing human brain
Pediatr. Res.
Aquaporins in brain: distribution, physiology, and pathophysiology
J. Cereb. Blood Flow Metab.
Inflammatory neurodegeneration mediated by nitric oxide, glutamate, and mitochondria
Mol. Neurobiol.
Differential effects of ethanol on glial signal transduction initiated by lipopolysaccharide and interferon-gamma
J. Neurosci. Res.
Acute renal failure in endotoxemia is caused by TNF acting directly on TNF receptor-1 in kidney
J. Immunol.
Blood–brain barrier breakdown in septic encephalopathy and brain tumours
J. Anat.
Physiology of the CSF and the Blood–Brain Barrier
An Introduction to the Blood–Brain Barrier
Immune function of astrocytes
Glia
GFAP and astrogliosis
Brain Pathol.
Glial fibrillary acidic protein: GFAP-thirty-one years (1969–2000)
Neurochem. Res.
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This work was supported by National Institutes of Health Grants R01DK41873, R01DK55357, and R01AI43579.