Tumor necrosis factor-alpha expression in ischemic neurons.

Abstract

Background and Purpose Tumor necrosis factor-a (TNF-a) is a cytokine with diverse proinflammatory actions, including endothelial leukocyte adhesion molecule expression. Since leukocytes infiltrate into ischemic brain lesions, the present study was conducted to examine whether TNF-a messenger RNA (mRNA) and peptide are expressed in the brain after experimental focal stroke and before leukocyte accumulation.Methods TNF-a mRNA and protein expression were monitored in the ischeraic and nonischemic cerebral cortex of rats after focal ischemia produced by permanent middle cerebral artery occlusion. The effect of TNF-a administered by microinjection into the brain cortex on leukocyte adherence to brain capillaries was also studied.Results Induction of TNF-a mRNA, normalized to a standard reference rat macrophage TNF-a mRNA, was detected as early as 1 hour after middle cerebral artery occlusion. TNF-a mRNA was elevated by 3 hours (29±6% versus 2±1% in sham-operated rats) only in the ischemic cortex, with peak expression at 12 hours (104±8%; P<.01). Five days after middle cerebral artery occlusion, TNF-a mRNA levels in ischemic cortex were still significantly elevated (38±5%; P<.05). Also, TNF-a mRNA expression was greater in the

The neuron-astrocyte-microglia triad in CA3 after chronic cerebral hypoperfusion in the rat: Protective effect of dipyridamole

“…It has been previously demonstrated that astrocytes have the capacity to secrete TNF-α (Chung and Benveniste 1990) and that TNF-α colocalized with neurofilaments in the cerebral cortex (Liu et al 1994) in response to a variety of stimuli such as ischemia. Dipyridamole, blocking the increased expression of the cytokine TNF-α in astrocytes, may decrease the proinflammatory milieu associated with the ischemic insult.…”

Slit modulates cerebrovascular inflammation and mediates neuroprotection against global cerebral ischemia

“…We tested the ability of Slit to modulate chemotaxis in the in vivo brain using two different proinflammatory stimuli: The cytokine TNFα (Carvalho-Tavares et al, 2000), and transient global ischemia, in which TNFα derived from resident cells (Liu et al, 1994;Gregersen et al, 2000;Botchkina et al, 1997;Uno et al, 1997;Feuerstein et al, 1998) and mediators of other inflammatory signaling cascades promote postischemic inflammation in the postcapillary venular system and in cerebral parenchyma. In both models, we found exogenously administered Slit to be potently effective in reducing cerebrovascular inflammation.…”

TNFR1 Upregulation Mediates Tolerance after Brain Ischemic Preconditioning

“…It is well known that TNF-a, which is expressed or released after ischemia (Liu et al, 1994), contributes to the damaging effects of this condition (for a review, see Shohami et al, 1999). However, additional evidences have demonstrated a direct, neuroprotective role of TNF-a (for a review, see Shohami et al, 1999).…”