Neuroactive Steroids in Acute Ischemic Stroke

Acute Ischemic Stroke (AIS) is one of the main causes of functional deterioration all over the world. Thus, 26% of patients older than 65 years still show limitations of daily activities 6 months after AIS, and 46% of these patients present cognitive deficiency of variable severity. AIS impose a burden on the way of living of patients and their families' in which depression emerges as a frequent neuropsychiatric disorder after the ischemic event. However, the occurrence of depression and other functional abnormalities on the first day following AIS is largely unknown. Neuroactive steroids have the capability to modulate in a positive or negative way the function of the nervous system. Changes in neuroactive steroid concentrations in plasma and nervous system have been described in degenerative diseases (Parkinson's disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis), autoimmune diseases (multiple sclerosis), epilepsy, and psychiatric disorders (depression and schizophrenia). In vulnerable regions such as the hippocampus and prefrontal cortex, high cortisol exposure damages the pyramidal neurons, decreases neurogenesis and impairs memory and learning. In a previous report, the investigators have demonstrated that old patients with AIS show changes in the plasma levels of cortisol and estradiol, which associate with low cognition, worse neurological status, and poor functional performance. The present report investigated changes of cortisol, brain-derived neurotrophic factor (BDNF) and nitrites (NO-2, nitric oxide soluble metabolites) after AIS. BDNF is a neurotrophin classically associated with learning and memory and negatively modulated by glucocorticoids, old age, and neurodegenerative diseases. In plasma, platelets are the major source of peripheral BDNF and levels of this neurotrophin are decreased in Alzheimer´s disease and depression. These disorders also show hypercortisolism and changes of cortisol dynamics suggesting that steroids, neurotrophins, and behavioral deficits may be functionally related. Regarding nitrites, cortisol treatment of human subjects significantly reduced plasma nitrate/nitrite concentrations. Therefore, considering that opposite changes occur in cortisol vs. BDNF and nitrites, the investigators aimed to determine in acute AIS patients (a) changes in plasma cortisol; (b) development of clinical, behavioral and functional deficits; (c) changes in plasma BDNF and nitrites, which may predict a neurotoxic effect of the excess cortisol in the ischemic nervous system.

Inclusion criteria

• Age between 60 and 90 years.
• Agreeing to participate in the study.
• Acute Ischemic Stroke of anterior vascular territory and/or posterior vascular territory whithin 24 hours of onset.
• Nine or more points in the Glasgow Coma Scale.
• Female patients in menopause.
• Patients without cognitive impairment before AIS according to family reference.
• Acceptance of the next of kin proxy in case the participant has sensory impairment.

Exclusion criteria

• Age <60 or > 90 years.
• Hemorrhagic Stroke.
• Transient ischemic attack (TIA).
• Acute Ischemic Stroke after 24 hours of onset.
• Hormonal replacement therapy.
• Immunosuppressive therapy in the last month before AIS (example corticosteroids).
• Acute infection (Example, pneumonia, urinary tract infection).
• Diagnosis of oncologic disease in the last month before AIS.
• Diagnosis of endocrinologic disease in the last month before AIS.
• Acute or long-term psychiatric illness.
• No agreement to participate in the study.
• Eight or less points in the Glasgow Coma Scale.
• Female patients with menstrual cycle or in the perimenopause.
• Patients with kidney or hepatic illness.
• Patients with cognitive impairment before AIS.