Neuroactive Steroids in Acute Ischemic Stroke
Condition: Ischemic Stroke; Cortisol; Hypersecretion
MeSH terms: Stroke; Ischemic Stroke; Cerebral Infarction; Ischemia
Study type: Observational

Summary: 
      Acute ischemic stroke (AIS) represents an economical challenge for health systems all over
      the globe. Despite increasing knowledge of the pathophysiology of AIS, there is no
      satisfactory treatment to revert the resulting brain damage. Changes of neuroactive steroids
      have been found in different neurological diseases. In this regard, the investigators have
      previously demonstrated that old patients with AIS show changes of plasma cortisol and
      estradiol concentrations, in that increased steroid levels are associated with a
      deterioration of neurological status and a worse cognitive decline. The present study
      assessed in patients with AIS if changes of behavior, brain-derived neurotrophic factor
      (BDNF) and nitrites (NO-2) (nitric oxide soluble metabolite) bear a relationship with the
      degree of hypercortisolism. To this purpose, the investigators recruited patients
      hospitalized at the Central Military Hospital emergency room within the first 24 hours of
      AIS. Subjects were divided into two groups, each one composed of 40 control subjects and 40
      AIS patients, including men and women. The neurological condition was assessed using the
      NIHSS and the cognitive status with the Montreal Cognitive Assessment (MoCA test). The
      emotional status was evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS),
      whereas the Modified Rankin Scale (MRS) was used to determine the functional condition. BDNF
      and NO-2 plasma levels were measured by ELISA and the Griess reaction method, respectively.
    

Detailed description: 
      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.
    

Intervention name(s): Behavioral tests
Intervention type(s): Other
Intervention description(s): We observed relationship between plasma levels of cortisol and neurological, cognitive, functional and emotional outcomes in patients with acute ischemic stroke.
Other intervention name(s): Plasma cortisol levels quantification; Plasma nitrites levels quantification; Plasma Brain Derived Neurotrophic Factor quantification
Intervention MeSH terms: Hydrocortisone
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        The subjects were between 60 and 90 years old, and were recruited randomly and distributed
        in two experimental groups: 1) a control group composed of subjects without physical or
        psychiatric disease, 2) an AIS group composed of subjects within the first 24 hours of the
        neurovascular event. The individuals were distributed in such a way that each experimental
        group contained 10 men and 10 women. Table 1 show the inclusion and exclusion criteria used
        for the AIS group.