Interleukin-1 in Stroke

Sobowale, Oluwaseun; Parry‐Jones, Adrian; Smith, Craig J.; Tyrrell, Pippa; Rothwell, Nancy J.; Allan, Stuart M.

doi:10.1161/strokeaha.115.010001

Cited by 102 publications

(50 citation statements)

References 71 publications

(85 reference statements)

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“…Further, there is evidence of progressive increase in perihematomal glucose metabolism in human ICH peaking at day 3, likely in response to increased perihematomal inflammatory cell infiltrate 34. It is therefore likely that hyperglycemia contributes to secondary neuronal injury by exacerbating the cerebral inflammatory milieu and oxidative stress,35 resulting in cellular injury in a process that is difficult to quantify clinically. The effects of hyperglycemia on brain injury are additive to primary injury resulting from the hematoma.…”

Section: Discussionmentioning

confidence: 99%

Persistent Hyperglycemia Is Associated With Increased Mortality After Intracerebral Hemorrhage

Putaala

Sharma

et al. 2017

JAHA

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BackgroundHyperglycemia may be associated with worse outcome after intracerebral hemorrhage (ICH). We assessed the association of early glycemic trajectory on ICH mortality and edema growth.Methods and ResultsWe included patients from the Helsinki ICH study with glucose measurements at least once between both 0 to 24 and 24 to 72 hours from onset. Hyperglycemia was defined as blood glucose ≥8 mmol/L (144 mg/dL) based on the local threshold for treatment. Glycemic trajectory was defined on maximum values 0 to 24 and 24 to 72 hours after ICH: (1) persistent normoglycemia in both epochs; (2) late hyperglycemia (only between 24 and 72 hours); (3) early hyperglycemia (only before 24 hours); and (4) persistent hyperglycemia in both epochs. Logistic regression with known predictors of outcome estimated the association of glycemic trajectory and 6‐month mortality. A generalized linear model assessed the association of glycemic trajectory and interpolated 72‐hour edema extension distance. A total of 576 patients met eligibility criteria, of whom 214 (37.2%) had persistent normoglycemia, 44 (7.6%) late hyperglycemia, 151 (26.2%) early hyperglycemia, and 167 (29.0%) persistent hyperglycemia. Six‐month mortality was higher in the persistent (51.1%) and early (26.3%) hyperglycemia groups than the normoglycemia (19.0%) and late hyperglycemia (3.6%) groups. Persistent hyperglycemia was associated with 6‐month mortality (odds ratio 3.675, 95% CI 1.989–6.792; P<0.001). Both univariate (P=0.426) and multivariable (P=0.493) generalized linear model analyses showed no association between glycemic trajectory and 72‐hour edema extension distance.ConclusionEarly hyperglycemia after ICH is harmful if it is persistent. Strategies to achieve glycemic control after ICH may influence patient outcome and need to be assessed in clinical trials.

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Section: Discussionmentioning

confidence: 99%

Persistent Hyperglycemia Is Associated With Increased Mortality After Intracerebral Hemorrhage

Putaala

Sharma

et al. 2017

JAHA

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“…During the propagation phase of inflammation, microglia and macrophages that are polarized towards the pro-inflammatory M1 phenotype secrete IL-1β and tumor necrosis factor alpha (TNF-α), which act to compromise the BBB (Rayasam et al, 2017). A small (n = 34) phase II randomized controlled trial provided promising results that IV delivery of a recombinant human IL-1 receptor antagonist (rhIL-1ra), over 72 h post-stroke might reduce plasma markers of inflammation (CRP and IL-6) and improve clinical outcome in those with cortical infarcts (Emsley et al, 2005; Sobowale et al, 2016). A larger (n=80) follow-up phase 2 randomized controlled trial showed that IL-1Ra was safe, well-tolerated, and reduced circulating inflammatory markers associated with worse clinical outcome (Smith et al, 2018).…”

Section: Recently Identified Therapeutic Aims and Therapiesmentioning

confidence: 99%

Targeting vascular inflammation in ischemic stroke: Recent developments on novel immunomodulatory approaches

Shekhar

Cunningham

Pabbidi

et al. 2018

European Journal of Pharmacology

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Ischemic stroke is a devastating and debilitating medical condition with limited therapeutic options. However, accumulating evidence indicates a central role of inflammation in all aspects of stroke including its initiation, the progression of injury, and recovery or wound healing. A central target of inflammation is disruption of the blood brain barrier or neurovascular unit. Here we discuss recent developments in identifying potential molecular targets and immunomodulatory approaches to preserve or protect barrier function and limit infarct damage and functional impairment. These include blocking harmful inflammatory signaling in endothelial cells, microglia/macrophages, or Th17/γδ T cells with biologics, third generation epoxyeicosatrienoic acid (EET) analogs with extended half-life, and miRNA antagomirs. Complementary beneficial pathways may be enhanced by miRNA mimetics or hyperbaric oxygenation. These immunomodulatory approaches could be used to greatly expand the therapeutic window for thrombolytic treatment with tissue plasminogen activator (t-PA). Moreover, nanoparticle technology allows for the selective targeting of endothelial cells for delivery of DNA/RNA oligonucleotides and neuroprotective drugs. In addition, although likely detrimental to the progression of ischemic stroke by inducing inflammation, oxidative stress, and neuronal cell death, 20-HETE may also reduce susceptibility of onset of ischemic stroke by maintaining autoregulation of cerebral blood flow. Although the interaction between inflammation and stroke is multifaceted, a better understanding of the mechanisms behind the pro-inflammatory state at all stages will hopefully help in developing novel immunomodulatory approaches to improve mortality and functional outcome of those inflicted with ischemic stroke.

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“…Beneficial effects of IL-1Ra in stroke are not fully cleared, but existing data suggest neuroprotective and vasculoprotective effects. In particular, neuroprotective effects are greater after co-administration with excitotoxins in the rat brain, whilst vasculoprotective effects are mainly linked to the prevention of BBB impairment and the blocking of neutrophil migration [254]. …”

Section: Anti-inflammatory Treatments In Is: Evidence From Pre-climentioning

confidence: 99%

Update on Inflammatory Biomarkers and Treatments in Ischemic Stroke

Bonaventura

Liberale

Vecchiè

et al. 2016

IJMS

125

100

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After an acute ischemic stroke (AIS), inflammatory processes are able to concomitantly induce both beneficial and detrimental effects. In this narrative review, we updated evidence on the inflammatory pathways and mediators that are investigated as promising therapeutic targets. We searched for papers on PubMed and MEDLINE up to August 2016. The terms searched alone or in combination were: ischemic stroke, inflammation, oxidative stress, ischemia reperfusion, innate immunity, adaptive immunity, autoimmunity. Inflammation in AIS is characterized by a storm of cytokines, chemokines, and Damage-Associated Molecular Patterns (DAMPs) released by several cells contributing to exacerbate the tissue injury both in the acute and reparative phases. Interestingly, many biomarkers have been studied, but none of these reflected the complexity of systemic immune response. Reperfusion therapies showed a good efficacy in the recovery after an AIS. New therapies appear promising both in pre-clinical and clinical studies, but still need more detailed studies to be translated in the ordinary clinical practice. In spite of clinical progresses, no beneficial long-term interventions targeting inflammation are currently available. Our knowledge about cells, biomarkers, and inflammatory markers is growing and is hoped to better evaluate the impact of new treatments, such as monoclonal antibodies and cell-based therapies.

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Interleukin-1 in Stroke

Cited by 102 publications

References 71 publications

Persistent Hyperglycemia Is Associated With Increased Mortality After Intracerebral Hemorrhage

Persistent Hyperglycemia Is Associated With Increased Mortality After Intracerebral Hemorrhage

Targeting vascular inflammation in ischemic stroke: Recent developments on novel immunomodulatory approaches

Update on Inflammatory Biomarkers and Treatments in Ischemic Stroke

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