Anti-inflammatory treatments for stroke: from bench to bedside

Abstract

So far, intravenous tissue-type plasminogen activator (tPA) and mechanical removal of arterial blood clot (thrombectomy) are the only available treatments for acute ischemic stroke. However, the short therapeutic window and the lack of specialized stroke unit care make the overall availability of both treatments limited. Additional agents to combine with tPA administration or thrombectomy to enhance efficacy and improve outcomes associated with stroke are needed. Stroke-induced inflammatory processes are a response to the tissue damage due to the absence of blood supply but have been proposed also as key contributors to all the stages of the ischemic stroke pathophysiology. Despite promising results in experimental studies, inflammation-modulating treatments have not yet been translated successfully into the clinical setting. This review will (a) describe the timing of the stroke immune pathophysiology; (b) detail the immune responses to stroke sift-through cell type; and (c) discuss the pitfalls on the translation from experimental studies to clinical trials testing the therapeutic pertinence of immune modulators.

Selective Apheresis of C-Reactive Protein for Treatment of Indications with Elevated CRP Concentrations

“…Other anti-inflammatory therapies have been investigated in AMI and ischemic stroke, such as colchicine [ 100 ], anti-CD18 agents [ 101 ] and agents targeting IL-1 or IL-6 [ 102 , 103 , 104 ]. CRP removal intends to stop the destruction of tissue already during the acute event.…”

Filling the gaps on stroke research: Focus on inflammation and immunity

“…A secondary huge cascade of inflammatory responses is orchestrated within minutes and persists among days or even weeks after. This process, especially during the first 48 h hours after stroke onset, has been deeply studied and reviewed during the last decades ( Anrather and Iadecola, 2016 , Shi et al, 2019 , Chamorro et al, 2016 , Drieu et al, 2018 ). The immune response is initiated immediately after the cell injury, by the release of different damage-associated molecular patterns (DAMPS), such as heat shock proteins, high mobility group box 1 and interleukin-33, purines (ATP, UTP, and their catabolites), peroxiredoxins, and mitochondrial-derived N-formyl peptides.…”

Elevated Tumor Necrosis Factor-a-induced Protein 8-like 2 mRNA from Peripheral Blood Mononuclear Cells in Patients with Acute Ischemic Stroke

“…Acute ischemic stroke is a multiple complex condition due to an abrupt loss of blood volume to the brain which will result in the rapid death of the brain tissue1. Stroke associated immunity and inflammation are demonstrated to play critical roles in all the stages of disease progression, including acute event of stroke and long term recovery after stroke2. Usually, the post-stroke inflammatory responses can be classified into three phases: the acute phase refers to the clearance of dead cells and the brain tissue injury accompanied by the activation of microglia or macrophages in the first hours after the onset of stroke; the subacute phase refers to the infiltration of leukocytes into the brain and the resolution of inflammation in the first days.…”

“…Usually, the post-stroke inflammatory responses can be classified into three phases: the acute phase refers to the clearance of dead cells and the brain tissue injury accompanied by the activation of microglia or macrophages in the first hours after the onset of stroke; the subacute phase refers to the infiltration of leukocytes into the brain and the resolution of inflammation in the first days. The later phase refers to tissue repair and glial scar by astrocytes and microglia in days and weeks after stroke 2-4. When ischemic stroke happens, the brain injury would be initiated by hypoxia inducible factor-1α and Notch intracellular domain, which can lead to the production of pro-inflammatory cytokines and the activation of apoptotic signaling pathways5.…”