Hypoxia and Inflammation
- SourceAvailable from: Matteo A Russo[Show abstract] [Hide abstract]
ABSTRACT: Hypoxia and Inflammation are strictly interconnected with important consequences at clinical and therapeutic level. While cell and tissue damage due to acute hypoxia mostly leads to cell necrosis, in chronic hypoxia, cells that are located closer to vessels are able to survive adapting their phenotype through the expression of a number of genes, including proinflammatory receptors for alarmins. These receptors are activated by alarmins released by necrotic cells and generate signals for master transcription factors such as NFkB, AP1, etc. which control hundreds of genes for innate immunity and damage repair. Clinical consequences of chronic inflammatory reparative response activation include cell and tissue remodeling, damage in the primary site and, the systemic involvement of distant organs and tissues. Thus every time a tissue environment become stably hypoxic, inflammation can be activated followed by chronic damage and cell death or repair with vessel proliferation and fibrosis. This pathway can occur in cancer, myocardial infarction and stroke, diabetes, obesity, neurodegenerative diseases, chronic and autoimmune diseases and age-related diseases. Interestingly, proinflammatory gene expression can be observed earlier in hypoxic tissue cells and, in addition, in activated resident or recruited leukocytes. Herewith, the reciprocal relationships between hypoxia and inflammation will be shortly reviewed to underline the possible therapeutic targets to control hypoxia-related inflammation in a number of epidemiologically important human diseases and conditions.
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ABSTRACT: Cerebral inflammation plays a crucial role in the pathophysiology of ischemic stroke and is involved in all stages of the ischemic cascade. Fullerene derivatives, such as fullerenol (OH-F) are radical scavengers acting as neuroprotective agents while glucosamine (GlcN) attenuates cerebral inflammation after stroke. We created novel glucosamine–fullerene conjugates (GlcN-F) to combine their protective effects and compared them to OH-F regarding stroke-induced cerebral inflammation and cellular damage. Fullerene derivatives or vehicle was administered intravenously in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) immediately after transient middle cerebral artery occlusion (tMCAO). Infarct size was determined at day 5 and neurological outcome at days 1 and 5 after tMCAO. CD68- and NeuN-staining were performed to determine immunoreactivity and neuronal survival respectively. Cytokine and toll like receptor 4 (TLR-4) expression was assessed using quantitative real-time PCR. Magnetic resonance imaging revealed a significant reduction of infarct volume in both, WKY and SHR that were treated with fullerene derivatives. Treated rats showed an amelioration of neurological symptoms as both OH-F and GlcN-F prevented neuronal loss in the perilesional area. Cerebral immunoreactivity was reduced in treated WKY and SHR. Expression of IL-1β and TLR-4 was attenuated in OH-F-treated WKY rats. In conclusion, OH-F and GlcN-F lead to a reduction of cellular damage and inflammation after stroke, rendering these compounds attractive therapeutics for stroke.Experimental Neurology 01/2015; accepted. DOI:10.1016/j.expneurol.2015.01.005 · 4.62 Impact Factor
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ABSTRACT: Early exposure to a fat-enriched diet programs the developmental profile, thus is associated with disease susceptibility in subsequent generations. Chronic low-grade inflammation, resulting from maternal high fat diet, is activated in the fetal environment and in many organs of offspring, including placenta, adipose, liver, vascular system and brain. The prevalence of an inflammatory response is highly associated with obesity incidence, cardiovascular diseases, NAFLD and brain damage. Substantial studies using high-fat model have consistently demonstrated the incidence of such inflammatory reactions; however, the potential contribution of active inflammation toward the physiological outcomes and developmental diseases are neither in depth discussed nor systemically integrated. Therefore, we aim to summarize the current findings in regards to how a maternal high fat diet influences the inflammatory status, and probable pathogenic effects on the offspring. More importantly, since limited research has been conducted to reveal the epigenetic regulation of these inflammatory markers by maternal high fat diet, we sincerely hope our review will not only outline the pathophysiological relevance of inflammation, but also identify a future direction for mechanistic investigation and clinical application.The Journal of Nutritional Biochemistry 08/2014; DOI:10.1016/j.jnutbio.2014.06.011 · 4.59 Impact Factor