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NEUROLOGY / EXPERIMENTAL RESEARCH
Overexpression of PGC-1α reduces inflammation
and protects against focal cerebral ischaemia/reperfusion injury
1
Department of Rehabilitation Therapy, School of Rehabilitation Medicine, Gannan Medical University, Ganzhou, Jiangxi, China
2
Department of Rehabilitation Therapy, Third Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
Submission date: 2020-03-05
Final revision date: 2020-07-05
Acceptance date: 2020-07-05
Online publication date: 2020-09-16
Publication date: 2026-04-12
Corresponding author
Youliang Wen
Department of Rehabilitation Therapy School of Rehabilitation Medicine Gannan Medical University Ganzhou, Jiangxi 341000 China
Department of Rehabilitation Therapy School of Rehabilitation Medicine Gannan Medical University Ganzhou, Jiangxi 341000 China
Arch Med Sci 2026;22(3):1849-1855
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Cerebral ischaemia and subsequent reperfusion can cause brain damage. Herein we investigate the impact of PGC-1α expression following I/R injury with overexpressed PGC-1α versus wild-type mice.
Material and methods:
Focal cerebral I/R was performed in the wild-type and transgenic mouse models. In both mouse groups we evaluated the redox status by measuring reactive oxygen species (ROS) content, infarct volumes, neurological scoring, protein (western blot analysis), and cytokine (enzyme-linked immunosorbent assay) expression.
Results:
The results showed that PGC-1α expression was significantly down-regulated in I/R injury compared to the sham mice. I/R injury increased ROS levels and further up-regulated apoptosis. PGC-1α-overexpressed mice down-regulated I/R injury-induced neurological deficit scores and infarct volume. In addition, compared to WT mice during I/R injury, PGC-1α-overexpressed mice significantly down-regulated inflammatory proteins (NF-κB, COX-2, NLRP3) and cytokine (TNF-α, IL-1β, IL-6) expressions. I/R injured mice showed severe decline in Nrf-2, HO-1, and NQO1 expressions.
Conclusions:
Importantly, PGC-1α/Nrf-2 suppression during cerebral I/R injury causes overall brain damage through increased oxidative stress, neuro-inflammation, and apoptosis. PGC-1α-overexpressed mice promoted cytoprotection through Nrf-2 regulation during cerebral ischaemia/reperfusion (I/R) injury. Thus, PGC-1α overexpression leads to lesser injury following ischaemia, thereby preserving mitochondrial activity. PGC-1α might act as therapeutic target protein and thereby protect against cerebral damage during I/R injury.
Cerebral ischaemia and subsequent reperfusion can cause brain damage. Herein we investigate the impact of PGC-1α expression following I/R injury with overexpressed PGC-1α versus wild-type mice.
Material and methods:
Focal cerebral I/R was performed in the wild-type and transgenic mouse models. In both mouse groups we evaluated the redox status by measuring reactive oxygen species (ROS) content, infarct volumes, neurological scoring, protein (western blot analysis), and cytokine (enzyme-linked immunosorbent assay) expression.
Results:
The results showed that PGC-1α expression was significantly down-regulated in I/R injury compared to the sham mice. I/R injury increased ROS levels and further up-regulated apoptosis. PGC-1α-overexpressed mice down-regulated I/R injury-induced neurological deficit scores and infarct volume. In addition, compared to WT mice during I/R injury, PGC-1α-overexpressed mice significantly down-regulated inflammatory proteins (NF-κB, COX-2, NLRP3) and cytokine (TNF-α, IL-1β, IL-6) expressions. I/R injured mice showed severe decline in Nrf-2, HO-1, and NQO1 expressions.
Conclusions:
Importantly, PGC-1α/Nrf-2 suppression during cerebral I/R injury causes overall brain damage through increased oxidative stress, neuro-inflammation, and apoptosis. PGC-1α-overexpressed mice promoted cytoprotection through Nrf-2 regulation during cerebral ischaemia/reperfusion (I/R) injury. Thus, PGC-1α overexpression leads to lesser injury following ischaemia, thereby preserving mitochondrial activity. PGC-1α might act as therapeutic target protein and thereby protect against cerebral damage during I/R injury.
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