AIM2 exacerbates hypoxic-ischemic brain damage in neonatal rats via promoting neuronal pyroptosis

IF 3.5 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin Pub Date : 2025-03-16 DOI:10.1016/j.brainresbull.2025.111305

Qianqian Li , Zengqin Wang , Fengli Li , Songlin Liu , Yuhong Ding , Junmei Yan , Xing Feng , Mei Li

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引用次数: 0

Abstract

Background

Pyroptosis has been reported to play a pathogenic role in neonatal hypoxic-ischemic brain damage (HIBD). Absence in melanoma 2 (AIM2) is an inflammasome involved in pyroptosis.

Objective

This study aimed to investigate the role of AIM2 in hypoxic-ischemia (HI)-induced pyroptosis and brain damage in a neonatal rat HIBD model.

Methods

In vivo, we injected a lentivirus that overexpressed or knocked down AIM2 into the lateral ventricle of rats within 24 h after birth and prepared a 7-day Sprague Dawley (SD) rat HIBD model. In vitro, we transfected lentiviruses overexpressing or knocking down AIM2 into cultured primary neurons and established an oxygen/glucose deprivation/reoxygenation (OGD/R) model. 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to determine infarct size. Hematoxylin and eosin and Nissl staining were used to evaluate morphological changes in the damaged brain. Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) assays were used to determine cell viability and toxicity. Pyroptosis was observed using transmission electron microscopy.

Results

AIM2 expression significantly increased in the HI-induced cortex of neonatal rats. Lentivirus-mediated overexpression of AIM2 significantly aggravates HI-induced brain injury and OGD/R-induced neuronal injury in vivo and in vitro. The lentivirus-mediated AIM2 knockdown significantly reversed these adverse effects. In addition, AIM2 overexpression increased HI-induced pyroptosis in neonatal rats in vivo and in vitro, whereas AIM2 knockdown suppressed HI-induced pyroptosis via the AIM2/Caspase-1/GSDMD pathway.

Conclusion

These findings show that the upregulation of AIM2 activates pyroptosis and plays a pathogenic role in neonatal HIBD.

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来源期刊

Brain Research Bulletin 医学-神经科学

CiteScore

6.90

自引率

2.60%

发文量

253

审稿时长

67 days

期刊介绍： The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.