Estradiol protects against hippocampal damage and impairments in fear conditioning resulting from transient global ischemia in mice

Abstract

Estradiol protects against hippocampal damage and some learning impairments resulting from transient global ischemia in rats. Here, we seek to validate a mouse model of transient global ischemia and evaluate the effects of estradiol on ischemia-induced hippocampal damage and behavioral impairments. Female C57Bl6/J mice were ovariectomized and implanted with estradiol-or oil-secreting capsules. One week later, mice experienced 15-min of 2-vessel occlusion (2-VO) or sham surgical procedures. Five days later, mice were exposed to a fear conditioning protocol in which a specific context and novel tone were paired with mild footshock. Twenty-four hours following conditioning, contextual fear was assessed by measuring freezing behavior in the conditioned context (in the absence of the tone). This was followed by assessment of cue fear by measuring freezing behavior to the conditioned tone presented in a new context. When tested in the conditioned context, oil-treated mice that experienced 2-VO exhibited a significant reduction in freezing behavior whereas estradiol-treated mice that experienced 2-VO showed no disruption in freezing behavior. Freezing behavior when presented with the conditioned tone was unaffected by either surgery or hormone treatment. These findings suggest that global ischemia causes impairments in performance on the hippocampally-dependent contextual fear task but not conditioned cue-based fear. Furthermore, estradiol prevented the ischemia-induced impairment in contextual fear conditioning. Fluoro-Jade (FJ) staining revealed neuronal degeneration throughout the dorsal hippocampus of mice that experienced 2-VO. Estradiol treatment reduced the number of FJ+ cells in CA1 and CA2, but not in CA3 or in the dentate gyrus. Together, these findings suggest that 15 min of global ischemia causes extensive hippocampal neurodegeneration and disrupts contextual fear conditioning processes in mice and that estradiol protects against these adverse effects.

Pre- and post-estrogen administration in global cerebral ischemia reduces blood-brain barrier breakdown in ovariectomized rats

“…However, estrogen treatment before and after ischemia-reperfusion following ovariectomy was seen to markedly restore the impairment to the BBB. In the same vein, previous studies demonstrated that estrogen treatment played a protective role against the hippocampus damage inflicted during global ischemia, and this result lends support to ours (4,12).…”

Inflammatory Response of Ischemic Tolerance in Circulating Plasma: Preconditioning-Induced by Transient Ischemic Attack (TIA) Phenomena in Acute Ischemia Patients (AIS)

“…Although, MMPs act as proinflammatory factor, they are also important for normal physiological function such as neuronal regeneration, cell proliferation, angiogenesis, and apoptosis (51). In addition, in our study previous TIA was related to cytokines downregulation implicated in molecular functions and biological processes previously described in the preconditioning phenomena like heat shock proteins (6,52), receptor of protein tyrosine kinase activity (53,54), and the response to estradiol (55).…”

A sex difference in oxidative stress and behavioral suppression induced by ethanol withdrawal in rats

“…E2-treated ovariectomized female rats performed the eye-blink test better than vehicle-treated ovariectomized rats during EW (our unpublished observation). E2 treatment significantly improved Rotarod performance of ischemic rats [59], suggesting that E2 exerts a protective role in cerebellar neurons.…”