Systemic inflammation affects reperfusion following transient cerebral ischaemia

Abstract

Reperfusion after stroke is critical for improved patient survival and recovery and can be achieved clinically through pharmacological (recombinant tissue plasminogen activator) or physical (endovascular intervention) means. Yet these approaches remain confined to a small percentage of stroke patients, often with incomplete reperfusion, and therefore there is an urgent need to learn more about the mechanisms underlying the no-reflow phenomenon that prevents restoration of adequate microvascular perfusion. Recent evidence suggests systemic inflammation as an important contributor to no-reflow and to further investigate this here we inject interleukin 1 (IL-1) i.p. 30 min prior to an ischaemic challenge using a remote filament to occlude the middle cerebral artery (MCA) in mice. Before, during and after the injection of IL-1 and occlusion we use two-dimensional optical imaging spectroscopy to record the spatial and temporal dynamics of oxyhaemoglobin concentration in the cortical areas supplied by the MCA. Our results reveal that systemic inflammation significantly reduces oxyhaemoglobin reperfusion as early as 3 h after filament removal compared to vehicle injected animals. CD41 immunohistochemistry shows a significant increase of hyper-coagulated platelets within the microvessels in the stroked cortex of the IL-1 group compared to vehicle. We also observed an increase of pathophysiological biomarkers of ischaemic damage including elevated microglial activation co-localized with interleukin 1α (IL-1α), increased blood brain barrier breakdown as shown by IgG infiltration and increased pyknotic morphological changes of cresyl violet stained neurons. These data confirm systemic inflammation as an underlying cause of no-reflow in the post-ischaemic brain and that appropriate anti-inflammatory approaches could be beneficial in treating ischaemic stroke.

Inflammation‐regulatory microRNAs: Valuable targets for intracranial atherosclerosis

“…These accumulated immune and inflammatory cells in the atherosclerotic arterial lesions can further secrete inflammatory cytokines that may cause the proliferation of smooth muscle cells (SMCs), thereby having a pro‐thrombotic influence on the endothelium (McColl, Allan, & Rothwell, ). Accordingly, growing evidence demonstrated that systemic inflammation throughout the whole period of ICAS dramatically affects the susceptibility to ICAS, as well as the outcomes (Anrather & Iadecola, ; Burrows et al, ; Murray et al, ).…”

Limb Remote Ischemic Conditioning: Mechanisms, Anesthetics, and the Potential for Expanding Therapeutic Options

“…These molecular events occur in the area of infarction called the “ischemic penumbra.” Though rendered functionally silent due to the decrease in blood flow, the penumbra remains metabolically active throughout this process, leading to the activation of apoptosis-like processes hours to days after the initial ischemic event ( 22 ). Multiple molecular consequences exist in the setting of reperfusion, including the no-reflow phenomenon ( 23 ), production of oxygen free radicals ( 24 ), lipid peroxidation, activation of neutrophils, formation of arachidonic acid metabolites, stimulation of NO, and activation of endothelin. Collectively, these mechanisms lead to I/R injury.…”

Berberine attenuates ischemia–reperfusion injury through inhibiting HMGB1 release and NF-κB nuclear translocation

“…Accordingly, a therapeutic strategy targeting HMGB1/NF-κB signaling may ameliorate cerebral stroke damage by restricting neuroinflammatory processes. Therefore, corresponding antiinflammatory drug development may be beneficial in treating ischemic stroke-induced brain injury [13,14].…”