Cell-to-Cell Interactions Mediating Functional Recovery after Stroke.

Claudia Alia,Cristina Spalletti,Daniele Cangi,Matteo Caleo,Livia Vignozzi,Marco Salluzzo,Verediana Massa

doi:10.3390/cells10113050

Claudia Alia, Cristina Spalletti + Show 5 more

Open Access

https://doi.org/10.3390/cells10113050

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Abstract

Ischemic damage in brain tissue triggers a cascade of molecular and structural plastic changes, thus influencing a wide range of cell-to-cell interactions. Understanding and manipulating this scenario of intercellular connections is the Holy Grail for post-stroke neurorehabilitation. Here, we discuss the main findings in the literature related to post-stroke alterations in cell-to-cell interactions, which may be either detrimental or supportive for functional recovery. We consider both neural and non-neural cells, starting from astrocytes and reactive astrogliosis and moving to the roles of the oligodendrocytes in the support of vulnerable neurons and sprouting inhibition. We discuss the controversial role of microglia in neural inflammation after injury and we conclude with the description of post-stroke alterations in pyramidal and GABAergic cells interactions. For all of these sections, we review not only the spontaneous evolution in cellular interactions after ischemic injury, but also the experimental strategies which have targeted these interactions and that are inspiring novel therapeutic strategies for clinical application.

Highlights

Adult disability caused by stroke is still one of the major problems for public health organizations over the world
We discuss the controversial role of microglia in neural inflammation after injury and we conclude with the description of post-stroke alterations in pyramidal and GABAergic cells interactions
The 2021 Heart Disease & Stroke Statistical Update from the American Health Association states that in 2019, 6.6 million deaths were attributable to cerebrovascular disease worldwide and a total of 3.3 million individuals died of ischemic stroke [2]

Summary

Introduction

Adult disability caused by stroke is still one of the major problems for public health organizations over the world. Understanding cell-to-cell interactions, among different cellular counterparts, and molecular mechanisms mediating both neuroprotection and plasticity, is fundamental for designing effective pharmacological strategies to improve neural repair and widen the window of plasticity for functional recovery in the ischemic brain. According to the American Heart the American Stroke Association Guidelines for the Early Management of Patients with Acute Ischemic Stroke, up to now there are neither pharmacological nor non-pharmacological treatments recommended as neuroprotective agents [13] This evidence suggests the necessity to go deeper inside the substrate of post stroke plastic rearrangements to identify more effective cellular and molecular targets. Perilesional tissue, in particular, is the theatre of a fundamental reorganization that can be the key for an improved functional recovery, if properly guided This reorganization involves almost the entire variety of cell populations in the brain tissue, including excitatory and inhibitory neurons and glial cells. We focus on cell-to-cell interactions involving astrocytes, oligodendrocytes, microglia, neurovascular components and pyramidal cells/interneurons, mediating support, plasticity or toxic effects to neurons in the damaged brain

Cellular and Molecular Support from the Neurovascular Unit after Ischemia

Role of Oligodendrocytes in Neural Support and Sprouting Inhibition

Microglial-Mediated Inflammation in Stroke: A Double-Edged Sword

Findings

Pyramidal and GABA-Ergic Neural Interactions in Post-Stroke Plasticity