Glial Cells as Therapeutic Approaches in Brain Ischemia-Reperfusion Injury

 What is your stroke hospital doing with this?

Glial Cells as Therapeutic Approaches in Brain Ischemia-Reperfusion Injury

Ivó H. Hernández 1,2,3 , 

Mario Villa-González 2,4 , 

Gerardo Martín 4, 

Manuel Soto 2,5
and María José Pérez-Álvarez 2,4,*





Citation: Hernández, I.H.;
Villa-González, M.; Martín, G.; Soto,
M.; Pérez-Álvarez, M.J. Glial Cells as
Therapeutic Approaches in Brain
Ischemia-Reperfusion Injury. Cells
2021, 10, 1639. https://doi.org/
10.3390/cells10071639
Academic Editors:
Antonio Rodríguez-Sinovas,
Marisol Ruiz-Meana and
Javier Inserte
Received: 29 May 2021
Accepted: 26 June 2021
Published: 30 June 2021
Publisher’s Note: MDPI stays neutral
with regard to jurisdictional claims in
published maps and institutional affiliations.
Copyright: © 2021 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
1 Genomic Instability Group, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain;
ihernandezh@cnio.es
2 Center for Molecular Biology “Severo Ochoa” (CBMSO) UAM/CSIC, 28049 Madrid, Spain;
mario.villa@uam.es (M.V.-G.); msoto@cbm.csic.es (M.S.)
3 Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III,
28031 Madrid, Spain
4 Departamento de Biología (Fisiología Animal), Facultad de Ciencias, Universidad Autónoma de Madrid,
28049 Madrid, Spain; gerardo.martin@estudiante.uam.es
5 Departamento de Biología Molecular, Facultad de Ciencias, Universidad Autónoma de Madrid,
28049 Madrid, Spain
* Correspondence: mj.perez@uam.es; Tel.: +34-91-497-2819

Abstract: 

Ischemic stroke is the second cause of mortality and the first cause of long-term disability constituting a serious socioeconomic burden worldwide. Approved treatments include thrombectomy and rtPA intravenous administration, which, despite their efficacy in some cases, are not suitable for a great proportion of patients. Glial cell-related therapies are progressively overcoming inefficient neuron-centered approaches in the preclinical phase. Exploiting the ability of microglia to naturally switch between detrimental and protective phenotypes represents a promising therapeutic treatment, in a similar way to what happens with astrocytes. However, the duality present in many of the roles of these cells upon ischemia poses a notorious difficulty in disentangling the precise pathways to target. Still, promoting M2/A2 microglia/astrocyte protective phenotypes and inhibiting M1/A1 neurotoxic profiles is globally rendering promising results in different in vivo models of stroke. On the other hand, described oligodendrogenesis after brain ischemia seems to be strictly beneficial, although these cells are the less studied players in the stroke paradigm and negative effects could be described for oligodendrocytes in the next years. Here, we review recent advances in understanding the precise role of mentioned glial cell types in the main pathological events of ischemic stroke, including inflammation, blood brain barrier integrity, excitotoxicity, reactive oxygen species management, metabolic support, and neurogenesis, among others, with a special attention to
tested therapeutic approaches.