MRI Monitoring of Neuroinflammation in Mouse Focal Ischemia

Wiart, Marlène; Davoust, Nathalie; Pialat, Jean‐Baptiste; Desestret, Virginie; Moucharrafie, S.; Cho, Tae-Hee; Mutin, M; Langlois, Jean‐Baptiste; Beuf, Olivier; Honnorat, Jérôme; Nighoghossian, Norbert; Berthezène, Yves

doi:10.1161/01.str.0000252159.05702.00

Cited by 93 publications

(91 citation statements)

References 34 publications

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“…Recently, several studies have reported the use of magnetic nanoparticles to identify inflammatory regions in stroke (4,(23)(24)(25). However, magnetic nanoparticles detect only macrophages/ microglia, which are thought to be less associated with acute inflammatory damage in stroke and do not correlate with infarct size, whereas neutrophil infiltration and MPO correlated well with infarct size (5).…”

Section: Discussionmentioning

confidence: 99%

Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase

Breckwoldt

Chen

Stangenberg³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

284

240

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Inflammation can extend ischemic brain injury and adversely affect outcome in experimental animal models. A key difficulty in translating animal studies to humans is the lack of a definitive method to confirm and track inflammation in the brain in vivo. Myeloperoxidase (MPO), a key inflammatory enzyme secreted by activated neutrophils and macrophages/microglia, can generate highly reactive oxygen species to cause additional damage in cerebral ischemia. We report here that a functional, enzyme-activatable MRI agent can accurately track the oxidative activity of MPO noninvasively in stroke in living animals. We found that MPO is widely distributed in ischemic tissues, correlates positively with infarct size, and is detected even 3 weeks postinfarction. The peak level of MPO activity, determined by activation of the MPO-sensing agent in vivo and confirmed by MPO activity and quantitative RT-PCR assays, occurred on day 3 after ischemia. Both neutrophils and macrophages/microglia contribute to secrete MPO in the ischemic brain, although neutrophils peak earlier (days 1-3) whereas macrophages/microglia are most abundant later (days 3-7). In contrast to the conventional MRI agent diethylenetriaminepentatacetate gadolinium, which reports blood-brain barrier disruption, MPO imaging is able to additionally track MPO activity and confirm inflammation on the molecular level in vivo, information that was previously only possible to obtain on ex vivo brain sections and impossible to assess in living human patients. Our findings could allow efficient noninvasive serial screening of therapies targeting inflammation and the use of MPO imaging as an imaging biomarker to risk-stratify patients.inflammation ͉ ischemia ͉ molecular imaging ͉ MRI ͉ brain

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Section: Discussionmentioning

confidence: 99%

Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase

Breckwoldt

Chen

Stangenberg³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

284

240

View full text Add to dashboard Cite

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“…The presence of these hyperintensities is also associated with weakened effect of antidepressant treatment, as well as long-term disability and neuro-cognitive decline (79). While the inflammatory response around the site of stroke is a well-known clinical observation (80) an animal model of focal ischemia demonstrated that inflammation extends far beyond the original site of ischemic injury, predominantly mediated by microglia (81). This is exactly the same manner by which stress has been attributed to the cause of neuroinflammation in various animal models (82), which has led to formulation of a neuroinflammatory hypothesis of depressive illness (83).…”

Section: Neuroinflammation and Its Implication In The Pathophysiologymentioning

confidence: 99%

Role of inflammatory cytokines in depression: Focus on interleukin-1β

et al. 2016

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Abstract. According to the World Health Organization, major depression will become the leading cause of disability worldwide by the year 2030. Despite extensive research into the mechanisms underlying this disease, the rate, prevalence and disease burden has been on the rise, particularly in the industrialized world. Epidemiological studies have shown biological and biochemical differences in disease characteristics and treatment responses in different age groups. Notable differences have been observed in the clinical presentation, co-prevalence with other diseases, interaction with the immune system and even in the outcome. Thus, there is an increased interest in characterizing these differences, particularly in terms of contribution of different factors, including age, cytokines and immunotherapy. Research into the possible mechanisms of these interactions may reveal novel opportunities for future pharmacotherapy. The aim of the present review is to document recent literature regarding the impact of inflammatory mechanisms on the pathophysiology of the depressive disorder.

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“…Another application for T 2 *-weighted images is the detection of susceptibility agents such as contrast agents. Systemic intravenous administration of ultrasmall superparamagnetic iron oxide nanoparticles for phagocytosis by activated blood-borne macrophages as a method to image the peripheral inflammatory response after stroke is one such application (Rausch et al, 2002;Wiart et al, 2007). However, evidence indicates this technique may not be so robust (Desestret et al, 2009;Henning et al, 2009), and more variability has been observed in the clinical setting Nighoghossian et al, 2007;Saleh et al, 2007).…”

Section: Relaxometrymentioning

confidence: 99%

Use of Magnetic Resonance Imaging to Predict Outcome after Stroke: A Review of Experimental and Clinical Evidence

Farr

Wegener

2010

J Cereb Blood Flow Metab

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Despite promising results in preclinical stroke research, translation of experimental data into clinical therapy has been difficult. One reason is the heterogeneity of the disease with outcomes ranging from complete recovery to continued decline. A successful treatment in one situation may be ineffective, or even harmful, in another. To overcome this, treatment must be tailored according to the individual based on identification of the risk of damage and estimation of potential recovery. Neuroimaging, particularly magnetic resonance imaging (MRI), could be the tool for a rapid comprehensive assessment in acute stroke with the potential to guide treatment decisions for a better clinical outcome. This review describes current MRI techniques used to characterize stroke in a preclinical research setting, as well as in the clinic. Furthermore, we will discuss current developments and the future potential of neuroimaging for stroke outcome prediction.

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MRI Monitoring of Neuroinflammation in Mouse Focal Ischemia

Cited by 93 publications

References 34 publications

Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase

Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase

Role of inflammatory cytokines in depression: Focus on interleukin-1β

Use of Magnetic Resonance Imaging to Predict Outcome after Stroke: A Review of Experimental and Clinical Evidence

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