Minocycline Prevents IL-6 Increase after Acute Ischemic Stroke

Switzer, Jeffrey A.; Sikora, Andrea; Ergul, Adviye; Waller, Jennifer L.; Hess, David C.; Fagan, Susan C.

doi:10.1007/s12975-012-0150-4

Cited by 29 publications

(20 citation statements)

References 15 publications

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“…It is known to cross the blood–brain barrier, and once in the brain can attenuate neuronal apoptosis, reduce the inflammation response by reducing microglial activation and migration of T-cells, and inhibit matrix metalloproteinase-9, which remodels extracellular matrix (Fagan et al 2011; Goldstein 2008; Machado et al 2006; Machado et al 2009; Matsukawa et al 2009; Switzer et al 2011; Switzer et al 2012; Yang et al 2015; Yrjanheikki et al 1999). In experimental models of acute ischemic stroke, minocycline shows neuroprotective effects and improved behavioral outcomes in males (Alano et al 2006; Li and McCullough 2009; Yrjanheikki et al 1999).…”

Section: Sex Differences In Treatment Efficacy In Preclinical Studiesmentioning

confidence: 99%

Sex differences in stroke therapies

Sohrabji

Park

Mahnke

2016

J of Neuroscience Research

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Stroke is the 5th leading cause of death and acquired disability in aged populations. Women are disproportionally affected by stroke, having a higher incidence and worse outcomes than men. Numerous preclinical studies have discovered novel therapies for the treatment of stroke, but almost all of these were found to be unsuccessful in clinical trials. Despite known sex differences in occurrence and severity of stroke, few therapeutics, both preclinically and clinically, take into account possible sex differences in treatment. Reanalysis of data from the only currently FDA-approved stroke therapy, tPA, has shown to not only improve stroke outcomes for both sexes, but to also show sexual dimorphism by more robust improvement in stroke outcome in females. Experimental evidence supports the inclusion of sex as a variable in the study of a number of novel stroke drugs and therapies, including preclinical studies of anti-inflammatory drugs (minocycline), stimulators of cell survival (IGF-1), and inhibitors of cell death pathways (pharmacological inhibition of PARP-1, NO production, and caspase activation), as well as in current clinical trials of stem cell therapy and cortical stimulation. Overall, study design and analyses in clinical trials, as well as in preclinical studies, must include both sexes equally, consider possible sex differences in the analyses, and report the differences/similarities in more systemized/structured way to translate promising therapies to both sexes and increase stroke recovery.

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Section: Sex Differences In Treatment Efficacy In Preclinical Studiesmentioning

confidence: 99%

Sex differences in stroke therapies

Sohrabji

Park

Mahnke

2016

J of Neuroscience Research

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“…The chemokine, CCL20, originates from the spleen after brain injury and has direct cytotoxic effects on neurons and oligodendrocytes [35]. Researchers are examining the action of signaling through cannabinoid and serotonin receptors [36] and the use of known anti-inflammatory compounds to alter the immune response to stroke [37]. Another interesting strategy is to activate the immune system’s anti-inflammatory response to counter the inflammatory one [38].…”

mentioning

confidence: 99%

Targeting the Peripheral Inflammatory Response to Stroke: Role of the Spleen

Pennypacker

2014

Transl. Stroke Res.

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“…Minocycline treatment also reduced AIS-induced levels of TNF-α and IL-1β, and increased levels of TGF-β, IL-10, anti-inlammatory M2 microglia/ macrophage markers, as well as cerebral perfusion [228]. Small clinical studies of minocycline in AIS have shown a decrease in IL-6 levels at 24 h post-AIS [229] and have proven safety in AIS patients both with and without tPA administration [230]. Lampl et al showed improvements in functional recovery as measured by the NIH stroke scale (NIHSS), modiied Rankin scale (mRS) and Barthel index(BI), in patients started on 200 mg of minocycline for 5 days within 6-24 h of stroke onset [231].…”

Section: The Antibiotic Minocycline In Ais and Tbimentioning

confidence: 90%

Roles of Pro- and Anti-inflammatory Cytokines in Traumatic Brain Injury and Acute Ischemic Stroke

Dugue¹,

Nath²,

Dugue³

et al. 2017

Mechanisms of Neuroinflammation

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This chapter will introduce the reader to the pathophysiology of two devastating neurologic events, traumatic brain injury (TBI) and acute ischemic stroke (AIS). Here we focus on the role of key pro-inlammatory and anti-inlammatory cytokines. Several experimental interventions have been found to modulate cytokine production and brain injury after AIS or TBI. Here minocycline, biological response modiiers, hormonal therapies, omega-3 faty acids, N-acetylcysteine, and cannabinoids will be discussed. In addition, the role of cytokine-induced inlammasomes in both TBI and AIS will be addressed and followed by discussion of pro-inlammatory cytokines (e.g., TNF-α, IL-1β, IL-18, and IFN-γ). Finally, the main anti-inlammatory cytokines, IL-33, IL-10, IL-6, and IL-4, will be discussed in the context of both TBI and AIS. It should be noted that the role of these cytokines is diverse and the dichotomization of classically pro-versus anti-inlammatory cytokines is being re-examined, as many of these cytokines have been found to play dual roles in TBI and AIS brain injury.Keywords: traumatic brain injury, ischemic stroke, cytokines, interleukins, inlammasome Pathophysiology of traumatic brain injuryTraumatic brain injury (TBI) is a major cause of death and disability worldwide [1,2]. It is one of the most commonly diagnosed neurological disorders in the United States, impacting people of a variety of ages and segments of society [3]. In Europe, the economic cost of © 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.TBI is over 33 billion euros per year [4]. Continued surveillance and research is being done to reduce primary and secondary TBI [as well as acute ischemic stroke(AIS)]-induced brain injury [1].The pathophysiology of TBI begins with the initial brain trauma (i.e., the primary injury). This primary injury results from mechanical damage that disrupts the blood-brain barrier (BBB), alters the vasculature and damages brain tissue. The resulting injured glia and neurons release their intracellular contents (i.e., damage-associated molecular paterns; (DAMPs)) into the extracellular space and activate neighboring glia and neurons. Activated glia and neurons then produce molecular signals that can both exacerbate and mend the acute injury and contribute to long-term recovery [5][6][7][8][9]. These downstream molecular and cellular processes (i.e., the secondary injury in TBI) are the focus of many pre-clinical and clinical therapeutic studies. Secondary injury in TBI involves a host of molecular and cellular responses to the The pathophysiology of AIS and TBI share common mechanisms. The initial insult in AIS, an occlusion of blood low resulting in a core infarct zone surrounded by a poorly perfused penumbra, versus the initial primary physical impact in TBI both result in pe...

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Minocycline Prevents IL-6 Increase after Acute Ischemic Stroke

Cited by 29 publications

References 15 publications

Sex differences in stroke therapies

Sex differences in stroke therapies

Targeting the Peripheral Inflammatory Response to Stroke: Role of the Spleen

Roles of Pro- and Anti-inflammatory Cytokines in Traumatic Brain Injury and Acute Ischemic Stroke

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