Our main findings include the following: (1) HI-induction in neonatal rats increased m6a methylation and reduced FTO expression; (2) FTO overexpression destabilized PTEN mRNA to modulate autophagy post-HI in neonatal rat hippocampi; and (3) hippocampal FTO overexpression attenuates HI-induced synaptic loss and cognitive impairment in neonatal rats. Here, PTEN is linked to Cognitive impairment.