The Neuroprotective Effects of Caffeine in a Neonatal Hypoxia-Ischemia Model are Regulated through the AMPK/mTOR Pathway

被引:1
作者
Bernis, Maria. E. [1 ,2 ]
Burkard, Hannah [1 ,2 ]
Bremer, Anna-Sophie [1 ,2 ]
Grzelak, Kora [1 ,2 ]
Zweyer, Margit [1 ,2 ]
Maes, Elke [1 ,2 ]
Nacarkucuk, Efe [1 ]
Kaibel, Hanna [1 ]
Hakvoort, Charlotte [1 ]
Mueller, Andreas [1 ]
Sabir, Hemmen [1 ,2 ]
机构
[1] Univ Bonn, Childrens Hosp, Dept Neonatol & Pediat Intens Care, Venusberg Campus 1, D-53127 Bonn, Germany
[2] Deutsch Zentrum Neurodegenerat Erkrankungen DZNE, Bonn, Germany
来源
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES | 2025年 / 21卷 / 01期
关键词
Neonatal; Hypoxia-Ischemia; AMPK; mTOR; Neuroprotection; Caffeine; ACTIVATED PROTEIN-KINASE; DEVELOPING RAT-BRAIN; FOCAL CEREBRAL-ISCHEMIA; WHITE-MATTER DAMAGE; THERAPEUTIC HYPOTHERMIA; NEURONAL APOPTOSIS; EARLY PHASE; AMPK; INJURY; INHIBITION;
D O I
10.7150/ijbs.101087
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:251 / 270
页数:20
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