TY  - JOUR
AU  - Bernis, Maria E
AU  - Burkard, Hannah
AU  - Bremer, Anna-Sophie
AU  - Grzelak, Kora
AU  - Zweyer, Margit
AU  - Maes, Elke
AU  - Nacarkucuk, Efe
AU  - Kaibel, Hanna
AU  - Hakvoort, Charlotte
AU  - Müller, Andreas
AU  - Sabir, Hemmen
TI  - The Neuroprotective Effects of Caffeine in a Neonatal Hypoxia-Ischemia Model are Regulated through the AMPK/mTOR Pathway.
JO  - International journal of biological sciences
VL  - 21
IS  - 1
SN  - 1449-2288
CY  - Lake Haven, N.S.W. [u.a.]
PB  - Ivyspring International Publ.
M1  - DZNE-2025-00010
SP  - 251 - 270
PY  - 2025
AB  - 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.
KW  - Caffeine: pharmacology
KW  - Caffeine: therapeutic use
KW  - Animals
KW  - Neuroprotective Agents: therapeutic use
KW  - Neuroprotective Agents: pharmacology
KW  - TOR Serine-Threonine Kinases: metabolism
KW  - Hypoxia-Ischemia, Brain: metabolism
KW  - Hypoxia-Ischemia, Brain: drug therapy
KW  - Rats
KW  - Animals, Newborn
KW  - Rats, Sprague-Dawley
KW  - AMP-Activated Protein Kinases: metabolism
KW  - Signal Transduction: drug effects
KW  - Disease Models, Animal
KW  - AMPK (Other)
KW  - Caffeine (Other)
KW  - Hypoxia-Ischemia (Other)
KW  - Neonatal (Other)
KW  - Neuroprotection (Other)
KW  - mTOR (Other)
KW  - Caffeine (NLM Chemicals)
KW  - Neuroprotective Agents (NLM Chemicals)
KW  - TOR Serine-Threonine Kinases (NLM Chemicals)
KW  - AMP-Activated Protein Kinases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39744433
C2  - pmc:PMC11667826
DO  - DOI:10.7150/ijbs.101087
UR  - https://pub.dzne.de/record/274029
ER  -