ArticleScientific reports2025
S100A8-CAMKK2-AMPK axis confers the protective effects of mild hypothermia against cerebral ischemia-reperfusion injury in rats.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Artificial hibernation: A new technique for protecting neural tissue and organs.Neural regeneration research · 2026Article
- Downregulation of Lgals3 Alleviates Inflammatory Response and Apoptosis in a Mouse Model of Cerebral Ischemia/Reperfusion Injury.Brain and behavior · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
To investigate the neuroprotective mechanism of mild hypothermia (MH) in ameliorating cerebral ischemia reperfusion (IR) injury. The Pulsinelli's four-vessel ligation method was utilized to establish a rat model of global cerebral IR injury. To investigate the role of S100A8 in MH treatment of cerebral IR injury, hippocampus-specific S100A8 loss or gain of function was achieved using an adeno-associated virus system. We examined the effect of S100A8 over-expression or knock-down on the function of the SH-SY5Y cell line subjected to oxygen-glucose deprivation reoxygenation (OGDR) injury under MH treatment and delved into the underlying mechanisms. MH significantly ameliorates IR-induced neurological injury in the brain. Similarly to MH, knock-down of S100A8 significantly reduced neuronal oxidative stress, attenuated mitochondrial damage, inhibited apoptosis, and improved cognitive function in IR rats. Conversely, over-expression of S100A8 attenuated MH's protective effect and aggravated brain IR injury. In vitro, low expression of S100A8 significantly inhibited the decline in mitochondrial membrane potential induced by OGDR, reduced oxidative stress response, and decreased cell apoptosis, acting as a protective agent nearly equivalent to MH in SH-SY5Y cells. However, over-expression of S100A8 significantly inhibited these protective effects of MH. Mechanistically, MH down-regulated S100A8 expression, enhancing mitochondrial function via activation of the CAMKK2/AMPK signaling pathway. Moreover, with MH treatment, the administration of CAMKK2 and AMPK inhibitors STO-609 and Dorsomorphin significantly increased oxidative stress, mitochondrial damage, and cell apoptosis, thereby diminishing MH's neuroprotective effect against cerebral IR injury. Our study identified S100A8 as a master regulator that enables MH to ameliorate neurological injury during the early stage of cerebral IR injury by enhancing mitochondrial function. By targeting the S100A8-initiated CAMKK2/AMPK signaling pathway, we may unlock a novel therapeutic intervention or develop a refined MH therapeutic strategy against cerebral IR injury.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.