Hypoxia-inducible factor-1: A new neuroprotective agent for the treatment of hyperglycemia after stroke

Acute hyperglycemia in ischemic stroke occurs in almost half of cases, inducing a worsening of the underlying pathophysiology. Hence, the management of acute hyperglycemia during the first hours following ischemic stroke requires well-defined strategies. Furthermore, the effect of hyperglycemia on stroke remains an unresolved paradoxical process whose possible causes are still unknown. The ischemic process involves the activation of multiple signaling pathways related to cell death and survival, which can be acutely altered by hyperglycemia, causing subsequent worsening of the ischemic process. In search of potential biological targets to combat this medical burden, the role of hypoxia-inducible factor appears as a novel neuroprotective agent that needs further investigation. Furthermore, hypoxia-inducible factor protein targets multiple pathways changing depending on factors such as the severity of hypoxia, the time elapsed after reperfusion and the specific cell type. In fact, the poor prognosis of ischemic stroke associated with acute hyperglycemia has been linked to alterations in hypoxia-inducible factor-1α protein function. Together, these findings support this transcription factor as a new therapeutic target to prevent the negative effect of hyperglycemia, opening new avenues for treatment in stroke.

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Publication Details

Journal
Neural Regeneration Research
Published
2026-01-02
DOI
https://doi.org/10.4103/nrr.nrr-d-25-00794
Primary Topic
Cancer, Hypoxia, and Metabolism
Type
article
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article

Hypoxia-inducible factor-1: A new neuroprotective agent for the treatment of hyperglycemia after stroke

José L. Zugaza, María Isabel Hernández, Abraham Martin
Neural Regeneration Research
Cancer, Hypoxia, and Metabolism
article

Hypoxia-inducible factor-1: A new neuroprotective agent for the treatment of hyperglycemia after stroke

José L. Zugaza, María Isabel Hernández, Abraham Martin
article en

Abstract

Acute hyperglycemia in ischemic stroke occurs in almost half of cases, inducing a worsening of the underlying pathophysiology. Hence, the management of acute hyperglycemia during the first hours following ischemic stroke requires well-defined strategies. Furthermore, the effect of hyperglycemia on stroke remains an unresolved paradoxical process whose possible causes are still unknown. The ischemic process involves the activation of multiple signaling pathways related to cell death and survival, which can be acutely altered by hyperglycemia, causing subsequent worsening of the ischemic process. In search of potential biological targets to combat this medical burden, the role of hypoxia-inducible factor appears as a novel neuroprotective agent that needs further investigation. Furthermore, hypoxia-inducible factor protein targets multiple pathways changing depending on factors such as the severity of hypoxia, the time elapsed after reperfusion and the specific cell type. In fact, the poor prognosis of ischemic stroke associated with acute hyperglycemia has been linked to alterations in hypoxia-inducible factor-1α protein function. Together, these findings support this transcription factor as a new therapeutic target to prevent the negative effect of hyperglycemia, opening new avenues for treatment in stroke.

Neural Regeneration Research
Ikerbasque (ES), Achucarro Basque Center for Neuroscience (ES), Universidad de León (ES)
Good health and well-being
Openalex Percentile: Top 95%
Cancer, Hypoxia, and Metabolism
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Hypoxia-inducible factor-1: A new neuroprotective agent for the treatment of hyperglycemia after stroke — José L. Zugaza, María Isabel Hernández, et al. · Neural Regeneration Research (2026) | TGRS Research Map | TGRS