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Updated: Jun 26, 2026
A Piglet Model of Neonatal Hypoxic-Ischemic Encephalopathy
Published on: May 16, 2015
Apelin-13 ameliorates hypoxic-ischemic brain damage and improves neurological function in neonatal rats by
Chenxu Miao1, Yue Li1, Chi Qin1
1Department of Radiology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Department of Clinical Research and Translational Medicine, Henan Joint International Research Laboratory of Neuroimaging, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Background:
Neonatal hypoxic-ischemic encephalopathy (HIE), caused by perinatal asphyxia, is a severe neurological disorder in which neuroinflammation contributes substantially to secondary brain injury and functional impairment. Although apelin-13 has demonstrated anti-inflammatory and neuroprotective effects in central nervous system injury models, its role in modulating neuroinflammation following HIE remains poorly understood. This study aimed to investigate the anti-inflammatory effects of apelin-13 in HIE and to elucidate the underlying mechanisms.
Methods:
Neonatal rats were subjected to hypoxic-ischemic (HI) injury and administered apelin-13 and/or the adenosine monophosphate-activated protein kinase (AMPK) inhibitor Compound C (CC) intraperitoneally at designated time points. At 24 h post-HI, cerebral damage was assessed by magnetic resonance imaging (MRI) and histopathological examination. Neurological function and white matter integrity were evaluated using neurobehavioral tests and diffusion tensor imaging (DTI). Molecular mechanisms involving inflammation and apoptosis were analyzed by Western blot and immunofluorescence.
Results:
Apelin-13 treatment reduced cerebral infarct volume, improved neurological function, and attenuated neuronal damage and apoptosis. It suppressed neuroglial activation and downregulated IL-1β, TNF-α, and caspase-3 expression. DTI revealed improved white matter microstructural integrity across multiple brain regions following apelin-13 intervention. Furthermore, these protective effects were mediated through AMPK phosphorylation and were reversed upon co-treatment with the AMPK inhibitor CC.
Conclusions:
Apelin-13 attenuated neuroinflammation, enhanced neurological function, and preserved white matter integrity in HI injury by promoting AMPK phosphorylation. These findings suggest that apelin-13 exerts potent neuroprotective effects against HI injury, identifying AMPK activation as a pivotal mechanism underlying this protection.
