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Astrocytes: Therapeutic targets for stroke
Jingxiu Li, Keyuan Gao, Lili Wang, Jiayue Wang, Mian Qin, Xinrui Wang, Kai Lian, Chao Li, Shan’e Gao, Chenxi Sun
2026, 21 (3):
1074-1088.
doi: 10.4103/NRR.NRR-D-24-01062
Stroke is the leading cause of mortality globally, ultimately leading to severe, lifelong neurological
impairments. Patients often suffer from a secondary cascade of damage, including neuroinflammation,
cytotoxicity, oxidative stress, and mitochondrial dysfunction. Regrettably, there is a paucity of
clinically available therapeutics to address these issues. Emerging evidence underscores the pivotal
roles of astrocytes, the most abundant glial cells in the brain, throughout the various stages of
ischemic stroke. In this comprehensive review, we initially provide an overview of the fundamental
physiological functions of astrocytes in the brain, emphasizing their critical role in modulating
neuronal homeostasis, synaptic activity, and blood–brain barrier integrity. We then delve into the
growing body of evidence that highlights the functional diversity and heterogeneity of astrocytes in
the context of ischemic stroke. Their well-established contributions to energy provision, metabolic
regulation, and neurotransmitter homeostasis, as well as their emerging roles in mitochondrial
recovery, neuroinflammation regulation, and oxidative stress modulation following ischemic injury,
are discussed in detail. We also explore the cellular and molecular mechanisms underpinning
these functions, with particular emphasis on recently identified targets within astrocytes that offer
promising prospects for therapeutic intervention. In the final section of this review, we offer a detailed
overview of the current therapeutic strategies targeting astrocytes in the treatment of ischemic
stroke. These astrocyte-targeting strategies are categorized into traditional small-molecule drugs,
microRNAs (miRNAs), stem cell-based therapies, cellular reprogramming, hydrogels, and extracellular
vesicles. By summarizing the current understanding of astrocyte functions and therapeutic targeting
approaches, we aim to highlight the critical roles of astrocytes during and after stroke, particularly
in the pathophysiological development in ischemic stroke. We also emphasize promising avenues
for novel, astrocyte-targeted therapeutics that could become clinically available options, ultimately
improving outcomes for patients with stroke.
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