Inflammation in Ischemic Stroke and Novel Therapeutic Strategies for Stroke Treatment

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Background

Inflammation in Ischemic Stroke and Novel Therapeutic Strategies for Stroke Treatment

Stroke is one of most frequent causes of death and long-term disability in the world. An ischemic stroke occurs due to a blockage in a major cerebral blood vessel, starving downstream tissue of oxygen and nutrients, which leads to cell death within minutes in the core of the infarct. Dying cells release pro-inflammatory signals that activate resident astrocytes/microglia and initiate immune cell infiltration from the periphery into the damaged tissue, contributing to blood-brain barrier disruption and exacerbating cell death in a process known as secondary inflammation that persists days to weeks after the initial insult. Understanding the molecular components of repair and damage mechanisms can be used as potential biomarkers in current and future treatment for stroke. Stem cell therapy is currently regarded as a hot research area, promising clinical therapeutic modality for ischemic stroke. The advent of cell-engineering approaches is expected to provide a new generation of stem cell-based therapies, greatly expanding their therapeutic utility for different traumatic and neurodegenerative diseases including ischemic stroke.

Increasing evidence has demonstrated the significance of the inflammatory response exacerbating brain injury in ischemic stroke and anti-inflammatory strategies are effective in ameliorating damage from experimental stroke, although it has yet to be explored at the clinical level. Targeting the inflammatory cascade offers a promising alternative to tissue plasminogen activator (tPA) or mechanical thrombectomy. These two strategies, approved by FDA for stroke treatment, have potential limitations or complications of their own including a narrow treatment time window (<4.5 hours) and risk of hemorrhagic transformation. More recently, derivatives of pluripotent stem cells are used with the aim of increasing the functional recovery of damaged brain tissue following post-ischemic stroke. These next-generation stem cells are being engineered with different therapeutic molecules to accelerate the repair of damaged tissues. The goal of this Research Topic is to collect manuscripts that elucidate the underlying roles of neuroinflammation in ischemic stroke and report novel therapeutic strategies, especially stem cell therapies, to improve stroke outcomes from experimental stroke models to clinical trials. This Research Topic is expected to provide deep understanding the role of neuroinflammation in the acute and recovery phases of ischemic stroke and gather research on the development of novel strategies for stroke treatment.

We therefore welcome submissions of Original Research, Systematic Reviews, Clinical Trials or Brief Research Reports, which explore the role of inflammation in the context of ischemic stroke or identify novel strategies to reduce stroke injuries. Potential topics include, but are not limited to:

• Role of astroglial/microglial activation and neutrophil and macrophage infiltration in ischemic brain

• Role of inflammatory mediators such as matrix metalloproteinases (MMPs), inducible nitric oxide synthase (iNOS), cytokines/chemokines and oxidative stress in ischemic stroke

• Transcriptional regulation of inflammation in ischemic stroke

• Effects of neuroinflammation on blood-brain barrier function in ischemic stroke

• Dual roles of inflammatory factors in the acute and recovery phases of ischemic stroke

• Assessment of novel approaches or therapeutic strategies for the treatment of ischemic stroke, and the potential use of different types of stem cells for cell-based therapy for ischemic stroke. Special consideration will be given to new engineering approaches and areas in which they will help broaden the utility and clinical application of stem cell therapy for ischemic stroke.

Keywords: ischemic stroke, neuroinflammation, blood-brain barrier, matrix metalloproteinases, oxidative stress, stem cells

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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