Supplementary Material for: Pretreatment with 17β-Estradiol Attenuates Cerebral Ischemia-Induced Blood-Brain Barrier Disruption in Aged Rats: Involvement of Antioxidant Signaling

Background/Aims: Blood-brain barrier (BBB) disruption is often induced in brain injury and particularly associated with cerebral ischemia in stroke. Estradiol (17β-estradiol 3-benzoate, E2), an endogenous steroid hormone, has been reported to play a protective role against cerebrovascular pathologies. Here we aimed to determine the potential effects of E2 on the integrity of BBB and brain damage following middle cerebral artery occlusion (MCAO). Methods: Aged (24- month-old) ovariectomized female rats were administered E2 for 2 months through daily intraperitoneal injections prior to induction of MCAO. Results: Compared to vehicle controls, E2 had a dose-dependent effect in reducing the severity of brain injuries while maintaining the integrity of the BBB in aged rats. The neuroprotective effects of E2 were associated with the rescued tight junction loss, decreased oxidative stress, and attenuated ERK activation in the ischemic brains. Conclusion: Our data suggest a beneficial role of E2 in aged stroke patients, associated with a protective effect of E2 against BBB disruption in aging-related brain ischemia.