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@ARTICLE{Bernis:274029,
author = {Bernis, Maria E and Burkard, Hannah and Bremer, Anna-Sophie
and Grzelak, Kora and Zweyer, Margit and Maes, Elke and
Nacarkucuk, Efe and Kaibel, Hanna and Hakvoort, Charlotte
and Müller, Andreas and Sabir, Hemmen},
title = {{T}he {N}europrotective {E}ffects of {C}affeine in a
{N}eonatal {H}ypoxia-{I}schemia {M}odel are {R}egulated
through the {AMPK}/m{TOR} {P}athway.},
journal = {International journal of biological sciences},
volume = {21},
number = {1},
issn = {1449-2288},
address = {Lake Haven, N.S.W. [u.a.]},
publisher = {Ivyspring International Publ.},
reportid = {DZNE-2025-00010},
pages = {251 - 270},
year = {2025},
abstract = {Neonatal hypoxic-ischemic encephalopathy (HIE) is the most
common cause of death and long-term disabilities in term
neonates. Caffeine exerts anti-inflammatory effects and has
been used in neonatal intensive care units in recent
decades. In our neonatal rat model of hypoxic-ischemic (HI)
brain injury, we demonstrated that a single daily dose of
caffeine (40 mg/kg) for 3 days post-HI reduced brain tissue
loss and microgliosis compared to the vehicle group. The
AMPK/mTOR pathway plays an important role in sensing the
stress responses following brain injury. However, the role
of mTOR in HI-associated brain damage remains unclear. A
detailed analysis of the AMPK/mTOR pathway in our model
revealed that this pathway plays a key role in
hypoxia-regulated neuroprotection and can be significantly
influenced by caffeine treatment. Targeting HI with caffeine
might offer effective neuroprotection, reduce mortality, and
improve functional outcomes in patients with HIE, especially
in low- and middle-income countries, where neuroprotective
treatment is urgently needed.},
keywords = {Caffeine: pharmacology / Caffeine: therapeutic use /
Animals / Neuroprotective Agents: therapeutic use /
Neuroprotective Agents: pharmacology / TOR Serine-Threonine
Kinases: metabolism / Hypoxia-Ischemia, Brain: metabolism /
Hypoxia-Ischemia, Brain: drug therapy / Rats / Animals,
Newborn / Rats, Sprague-Dawley / AMP-Activated Protein
Kinases: metabolism / Signal Transduction: drug effects /
Disease Models, Animal / AMPK (Other) / Caffeine (Other) /
Hypoxia-Ischemia (Other) / Neonatal (Other) /
Neuroprotection (Other) / mTOR (Other) / Caffeine (NLM
Chemicals) / Neuroprotective Agents (NLM Chemicals) / TOR
Serine-Threonine Kinases (NLM Chemicals) / AMP-Activated
Protein Kinases (NLM Chemicals)},
cin = {AG Sabir / AG Salomoni},
ddc = {570},
cid = {I:(DE-2719)5000032 / I:(DE-2719)1013032},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39744433},
pmc = {pmc:PMC11667826},
doi = {10.7150/ijbs.101087},
url = {https://pub.dzne.de/record/274029},
}