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

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.