Consistent with the above studies, herein, we found that when ICA was administered to HIBD newborn mice at the same time as intracerebroventricular injection of the ERα inhibitor MPP and ERβ inhibitor PHTPP, the neuroprotective effects of ICA pretreatment were significantly reversed; the cerebral infarct volume and brain water content were increased; the body weights were significantly reduced, and neurological impairment was significantly aggravated. This evidence concerns the gene ESR2 and cerebral infarction.