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To be or not to be (inflamed)-is that the question in anti-inflammatory drug therapy of neurodegenerative disorders? Trends in Pharmacological Sciences, 26, 517-525

Department of Pharmacology, University of Sassari Medical School, Sassari, Sardinia, Italy.
Trends in Pharmacological Sciences (Impact Factor: 9.99). 11/2005; 26(10):517-25. DOI: 10.1016/j.tips.2005.08.007
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ABSTRACT A sustained inflammatory reaction is present in acute (e.g. stroke) and chronic (e.g. Alzheimer's disease, Parkinson's disease and multiple sclerosis) neurodegenerative disorders. Inflammation, which is fostered by both residential glial cells and blood-circulating cells that infiltrate the diseased brain, probably starts as a time- and site-specific defense mechanism that could later evolve into a destructive and uncontrolled reaction. In this article, we review the crucial dichotomy of brain inflammation, where failure to resolve an acute beneficial response could lead to a vicious and anarchic state of chronic activation. The possible use of non-steroidal anti-inflammatory drugs for the management of neurodegenerative diseases is discussed in light of recent data demonstrating a neuroprotective role of local innate and adaptive immune responses. Novel therapeutic approaches must rely on potentiation of endogenous anti-inflammatory pathways, identification of early markers of neuronal deterioration and a combination treatment involving immune modulation and anti-inflammatory therapies.

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    • "Inflammation is also associated with neurocognitive dysfunction (Krabbe, Pedersen, & Bruunsgaard, 2004; Marsland et al., 2006; Teunissen et al., 2003). Novel antiinflammatory therapies are currently being tested and used in individuals with chronic inflammatory conditions (Canvin & el-Gabalawy, 1999; Gorelick, 2010; Marchetti & Abbracchio, 2005; Raber et al., 1998). In line with this notion, researchers have begun to explore the use of marijuana in the reduction of inflammatory processes (Albayram et al., 2011; Cabral & Griffin-Thomas, 2009; Jackson, Diemel, Pryce, & Baker, 2005). "
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    ABSTRACT: The purpose of the current study was to determine if self-reported lifetime marijuana use moderates the relationship between interleukin-6 (IL-6) and neurocognitive performance. Participants included 161 African American adults (50.3% women), with a mean age of 45.24 (SD=11.34). Serum was drawn upon entry into the study and participants completed a demographic questionnaire, which included drug use history, and a battery of neuropsychological tests. Using multiple regression analyses and adjusting for demographic covariates, the interaction term comprised of IL-6 and self-reported lifetime marijuana use was significantly associated with poorer performance on the Written (β=-.116; SE=.059; p=.049) and Oral trials (β=-.143; SE=.062; p=.022) of the Symbol Digit Modalities Test, as well as the Trail Making Test trial A (β=.157; SE=.071; p=.028). Current findings support previous literature, which presents the inverse relationship between IL-6 and neurocognitive dysfunction. The potential protective properties of marijuana use in African Americans, who are at increased risk for inflammatory diseases, are discussed. (JINS, 2014, 20, 773-783).
    Journal of the International Neuropsychological Society 09/2014; 20(8):773-83. DOI:10.1017/S1355617714000691 · 3.01 Impact Factor
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    • "Several previous studies have demonstrated that both astrocytes and microglia were activated under PD conditions, and their roles are very dynamic and cell-type dependent [41]–[43]. Astrocytes and microglia may exert harmful effects by producing pro-inflammatory and cytotoxic mediators that kill neurons or form scars that barricade axonal regeneration, but in certain circumstances, these cells can turn into highly protective cells, and produce anti-inflammatory cytokines, express and release a panel of pro-survival, neurotrophic and pro-regenerative factors, thereby facilitating neuronal recovery and repair [44]–[46]. To understand the different cell type interactions and to elucidate the molecular mechanism underlying the neuroprotective effect of SalB, we used an in vitro system containing the three main PD-related cell types, namely neurons, microglia, and astrocytes. "
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    PLoS ONE 07/2014; 9(7):e101668. DOI:10.1371/journal.pone.0101668 · 3.23 Impact Factor
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    • "Activation of microglia was reported to be neuroprotective in ischemic models (Lalancette-Hébert et al., 2007), despite its harmful effects to neurons when activation is excessive (Heppner et al., 2005; Marchetti and Abbracchio, 2005). A proper control of microglial reactivity by SERMs may represent a potential therapeutic strategy in brain injuries. "
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