17β-Estradiol Attenuates Intracerebral Hemorrhage-Induced Blood-Brain Barrier Injury and Oxidative Stress Through...

Area of Science:

• Neuroscience
• Endocrinology
• Cellular Biology

Background:

• Estrogen demonstrates neuroprotective properties in models of brain injury.
• Steroid receptor cofactor 3 (SRC3) is a key mediator of estrogen signaling pathways.
• Intracerebral hemorrhage (ICH) is a severe form of stroke with limited treatment options.

Purpose of the Study:

• To investigate the role of SRC3 in the neuroprotective effects of 17ß-estradiol (E2) following ICH.
• To elucidate the mechanisms by which E2 exerts neuroprotection in an ICH mouse model, focusing on SRC3 and the PI3K/Akt pathway.

Main Methods:

• Ovariectomized female mice underwent ICH induction via autologous blood injection and subsequent E2 treatment.
• Assessment of brain damage included neurological deficit scores, brain water content, and oxidative stress markers.
• Blood-brain barrier (BBB) integrity was evaluated using Evan's blue extravasation and key tight junction protein levels (claudin-5, ZO-1, occludin).
• SRC3 expression and PI3K/Akt signaling were analyzed in ICH mice treated with E2.
• Neurological outcomes in SRC3-deficient mice treated with E2 post-ICH were examined to determine SRC3's necessity.

Main Results:

• E2 treatment significantly reduced ICH-induced brain edema, neurological deficits, and oxidative stress.
• E2 administration preserved blood-brain barrier (BBB) integrity.
• E2 enhanced both SRC3 expression and the activation of the PI3K/Akt signaling pathway.
• SRC3 deficiency abrogated the neuroprotective effects of E2, including improvements in neurological deficits, brain edema, and BBB integrity.

Conclusions:

• 17ß-estradiol (E2) effectively mitigates brain injury associated with intracerebral hemorrhage (ICH).
• Steroid receptor cofactor 3 (SRC3) is essential for mediating the neuroprotective actions of E2 in the context of ICH.
• Targeting the E2-SRC3 pathway may represent a novel therapeutic strategy for managing ICH.