Neuroactive Steroids in Acute Ischemic Stroke: Association with Cognitive, Functional, and Neurological Outcomes

Abstract

Despite several scientific and technological advances, there is no single neuroprotective treatment that can reverse the brain damage after acute ischemic stroke (AIS). Neuroactive steroids are cholesterol-derived hormones that have the ability to modulate the normal and pathologic nervous system employing genomic and nongenomic mechanisms. In this work, we first investigated if AIS affects the plasma concentration of 5 neuroactive steroids (cortisol, estradiol, progesterone, testosterone, and 3α-androstenediol glucuronide). Second, we studied if levels of circulating steroids associate with neurological, cognitive, and functional outcome in a cohort of 60- to 90 year-old male and female patients with AIS. For this purpose, we recruited patients who were hospitalized at the Emergency Room of the Central Military Hospital within the first 24 h after stroke onset. We designed 2 experimental groups, each one composed of 30 control subjects and 30 AIS patients, both males and females. The assessment of neurological deficit was performed with the NIHSS and the tests used for the functional and cognitive status were: (1) modified Rankin Scale; (2) Photo test, and (3) abbreviated Pfeiffer's mental status questionnaire. We observed a significant difference in plasma concentration of cortisol and estradiol between both experimental groups. In the AIS group, higher levels of these neuroactive steroids were associated with more pronounced neurological, cognitive and functional deficits in women compared to men. We propose that in elderly patients, high levels of circulating neuroactive steroids like cortisol and estradiol could potentiate AIS-mediated neuropathology in the ischemic and penumbra areas.

Sex differences in steroid levels and steroidogenesis in the nervous system: Physiopathological role

“…Neuroactive steroid plasma levels are also affected by acute ischemic stroke in a sex specific way. Thus, an increase in 17β-E plasma levels occurs in women but not in men (Casas et al, 2017).…”

Neuroprotection - New Approaches and Prospects

“…Curcumin-solid lipid nanoparticles seem to be effective for MD and central oxidative stress [214]. In addition, curcumin and piperine co-loaded glycerol mono-oleate nanoparticles can interfere with Syn aggregation, reducing oxidative damage and apoptosis [215]. Curcumin was also taken in consideration for intranasal delivery to the central nervous system by nanoemulsions.…”

Serum Cortisol Is Associated With Cerebral Small Vessel Disease-Related Brain Changes and Cognitive Impairment

“…Exposure to high levels of cortisol also increases the risk and deteriorates the prognosis of acute cardiovascular associated with cerebral hypoperfusion, endothelial dysfunction and atherosclerosis such as stroke, transient ischemic attack and coronary heart disease (Walker, 2007;Everson-Rose et al, 2014;Casas et al, 2017). At present, endothelial dysfunction, bloodbrain barrier and amyloid deposition are widely considered to be important mechanisms leading to CSVD, which may result in the occurrence of CSVD together with genetic factors and chronic hypoperfusion (Wardlaw et al, 2013b).…”