The release of tumor necrosis factor–α is associated with ischemic tolerance in human stroke

Abstract

Tumor necrosis factor (TNF)-alpha overexpression has been related to experimental ischemic tolerance when transient ischemia precedes cerebral infarction. We investigated TNF-alpha and interleukin (IL)-6 plasma concentrations in 283 patients with an acute stroke within 24 hours after symptom onset. An ipsilateral transient ischemic attack (TIA) within 72 hours before stroke was recorded in 38 patients. The infarct volume measured on computed tomography on days 4 to 7 and the frequency of poor outcome (Barthel Index score < 85) at 3 months were significantly lower in patients with prior TIA. Plasma concentrations of TNF-alpha were higher (42.5 +/- 9.9 vs 13.1 +/- 6.4pg/ml, p < 0.0001) and IL-6 levels were lower (10.1 +/- 6.2 vs 28.3 +/- 17.3pg/ml, p < 0.0001) in patients with prior TIA. A new variable termed TNF-alpha/IL-6 index was considered positive when TNF-alpha was greater than 30pg/ml and IL-6 was less than 30pg/ml. Positive TNF-alpha/IL-6 index was found in 92% of patients with prior TIA and in 1% of those without. TNF-alpha/IL-6 index (p = 0.0003) and TIA (p = 0.0001) were associated with good outcome in logistic regression analysis after adjusting for potential confounding factors. Ischemic tolerance in acute stroke is associated with increased plasma levels of TNF-alpha in the presence of reduced concentrations of IL-6.

Spectacular Shrinking Deficit: Insights from Multimodal Magnetic Resonance Imaging after Embolic Middle Cerebral Artery Occlusion in Sprague—Dawley Rats

“…This seems to be of special interest given the contradicting significance attributed to brief cerebral ischemia. Whereas some studies found that transient cerebral ischemia may improve stroke outcome by serving as a preconditioning stimulus that triggers neuroprotective pathways in the brain (Castillo et al, 2003;Wegener et al, 2004), others demonstrated secondary deterioration on MRI (Fujioka et al, 1999a) or neurological function (Johnston et al, 2003;Smith et al, 2005) similar to the herein observed pathology. Hence, withholding treatment in these patients should be reconsidered and more aggressive interventions may be indicated in patients with rapidly improving symptoms, who currently are often treated with little urgency or concern (Johnston et al, 2003;Smith et al, 2005).…”

In VitroIschemic Tolerance Involves Upregulation of Glutamate Transport Partly Mediated by the TACE/ADAM17-Tumor Necrosis Factor-α Pathway

“…Indeed, Kitagawa et al (1990) found that gerbils subjected to sublethal transient global ischemia exhibited reduced hippocampal CA1 neuronal death after a more severe ischemic insult 24 -48 hr later, and similar findings have been reported by others (for review, see Barone et al, 1998;Kirino, 2002). Ischemic tolerance also has been demonstrated in human clinical practice, because less severe strokes have been described in patients with prior ipsilateral transient ischemic attacks within a short period of time (Weih et al, 1999;Moncayo et al, 2000;Castillo et al, 2003). The remarkable protection induced by IPC makes this an attractive target for potential therapeutic development.…”

“…These data are in agreement with those showing that TNF-␣ pretreatment induces protective effects against focal ischemia (Nawashiro et al, 1997) and that expression of TNF-␣ mRNA is augmented after preconditioning . Other reports have also shown the protective role of TNF-␣ in IPC in animals both in vitro and in vivo (Liu et al, 2000;Cárdenas et al, 2002;Ginis et al, 2002) and in humans (Castillo et al, 2003).…”

Ultrastructural Changes, Nuclear Factor-κB Activation, and Tumor Necrosis Factor-α Expression if Brain AfterAcute Normovolemic Hemodilution and Controlled Hypotension in Rats

“…Recent data suggest that several inflammatory cytokines may be synthesized and secreted by several central nervous system cell types including microglia, astrocytes, and neurons (20). These cytokines could influence both progression of injury and regulation of wound healing in the brain.…”