The roles of TNF in brain dysfunction and disease

Tumor Necrosis Factor-Induced Cerebral Insulin Resistance in Alzheimer's Disease Links Numerous Treatment Rationales

“…Although some still regard inflammation in AD as solely a secondary downstream consequence of A␤ generation (as reviewed by Zotova et al, 2010), evidence continues to accumulate (for review, see Clark et al, 2010) for excess cerebral TNF, and therefore the cascade of cytokines it initiates, to be viewed as an essential preillness step in its pathogenesis. Some time ago, higher cerebrospinal fluid (CSF) levels of TNF from 56 subjects with mild cognitive impairment, but not 25 age-matched controls subjects, were reported to predict which patients would develop frank AD (Tarkowski et al, 2003).…”

“…Cerebral ischemia has also been reported (Wen et al, 2004a) to induce aberrant neuronal cell cycle re-entry that can be reduced by 17␤-estradiol, an inhibitor of TNF (Hsu et al, 2000), a cytokine with a long history of interfering with mitosis (Darzynkiewicz et al, 1984) and more recently demonstrated to cause aneuploidy (Wu et al, 2011), the phenomenon that sets the scene for aberrant cell cycling and thus apoptosis. As recently reviewed by Clark et al (2010), trauma triggers release of inflammatory cytokines through the action of mitochondrial DNA set free from disrupted cells . In infectious diseases, much evidence exists for the direct induction of TNF by products of the pathogen, beginning with the example of bacterial lipopolysaccharide in the original TNF article (Carswell et al, 1975).…”

Neurochemistry in the Pathophysiology of Septic Encephalopathy

“…Our approach successfully demonstrates the synaptic functional deficiency in septic encephalopathy and relevance of interleukin antagonist for the deficiency. However, there are still unclear for the following points: 1) effects of other inflammatory mediators, such as high mobility group box (HMGB)-1 (Zhao X et al, 2011) and tumor necrosis factor (Clark IA et al, 2010) which are expressed abundantly in the brain, to synaptic function, 2) How is the consequence of sepsis on the other brain regions except hippocampus. In following section, relevance of autonomic nervous system and a novel technology for the treatment and prescription of septic encephalopathy in the future are discussed.…”

Pediatric Cerebral Malaria: A Scourge of Africa

“…This study was the first to document that CSF TNF-a production is associated with neurologic and cognitive sequelae. The mechanisms by which the excessive TNF-a in the brain can lead to neurological injury is well documented elsewhere [102].…”