Neuroactive Steroids in Acute Ischemic Stroke (Cortisol)
2017年8月7日 更新者:Sebastian Casas、Hospital Militar Central, Argentina
Changes in Plasma Cortisol, Brain-derived Neurotrophic Factor, and Nitrites in Patients With Acute Ischemic Stroke
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.
調査の概要
詳細な説明
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.
研究の種類
観察的
入学 (実際)
40
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
60年~90年 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
サンプリング方法
確率サンプル
調査対象母集団
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.
説明
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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか?
デザインの詳細
- 観測モデル:ケースコントロール
- 時間の展望:見込みのある
コホートと介入
グループ/コホート |
介入・治療 |
---|---|
Control group
A control group composed of subjects without physical or psychiatric disease.
|
We observed relationship between plasma levels of cortisol and neurological, cognitive, functional and emotional outcomes in patients with acute ischemic stroke.
他の名前:
|
Acute Ischemic Stroke group
An AIS group composed of subjects within the first 24 hours of the neurovascular event.
|
We observed relationship between plasma levels of cortisol and neurological, cognitive, functional and emotional outcomes in patients with acute ischemic stroke.
他の名前:
|
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Neurological déficit
時間枠:Into 24 hours of Acute Ischemic Stroke
|
The neurological state during AIS was quantified by the National Institute of Health stroke scale at the time of hospitalization (NIHSS,available at http://www.ninds.nih.gov/doctors/NIH_Stroke_Scale.pdf
|
Into 24 hours of Acute Ischemic Stroke
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Cognition
時間枠:Into 24 hours of Acute Ischemic Stroke
|
The cognitive test used was the Montreal Cognitive Assessment (MoCA test).
|
Into 24 hours of Acute Ischemic Stroke
|
Emotional state
時間枠:Into 24 hours of Acute Ischemic Stroke
|
Patients with AIS were evaluated on the Montgomery-Asberg depression scale (MADRS)
|
Into 24 hours of Acute Ischemic Stroke
|
Functional dependency of daily life activities
時間枠:Into 24 hours of Acute Ischemic Stroke
|
The functional state of the AIS patients was assessed by the modified Rankin scale at the time of entering the admission floor.
|
Into 24 hours of Acute Ischemic Stroke
|
Cortisol
時間枠:Into 24 hours of Acute Ischemic Stroke
|
Plasma cortisol concentration was determined by chemiluminescent microparticle immunoassay (CMIA), using Team Architect i1000, Abbott Laboratories, Middletown, USA.
|
Into 24 hours of Acute Ischemic Stroke
|
Quantification of nitrites concentration (NO-2)
時間枠:Into 24 hours of Acute Ischemic Stroke
|
Levels of NO-2, nitric oxide soluble metabolite (ON.) in water, were measured spectrophotometrically at 543 nm absorbance by the Griess reactio
|
Into 24 hours of Acute Ischemic Stroke
|
BDNF quantification in plasma
時間枠:Into 24 hours of Acute Ischemic Stroke
|
Plasma BDNF concentration was measured by enzyme-linked immunosorbent assay (ELISA)
|
Into 24 hours of Acute Ischemic Stroke
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
捜査官
- 主任研究者:Sebastian M Casas, Ph.D., MD.、Hospital Militar Central Cir My ¨Dr. Cosme Argerich¨
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- Casas S, Giuliani F, Cremaschi F, Yunes R, Cabrera R. Neuromodulatory effect of progesterone on the dopaminergic, glutamatergic, and GABAergic activities in a male rat model of Parkinson's disease. Neurol Res. 2013 Sep;35(7):719-25. doi: 10.1179/1743132812Y.0000000142. Epub 2013 Mar 5.
- Yunes R, Casas S, Gaglio E, Cabrera R. Progesterone Exerts a Neuromodulatory Effect on Turning Behavior of Hemiparkinsonian Male Rats: Expression of 3 alpha -Hydroxysteroid Oxidoreductase and Allopregnanolone as Suggestive of GABAA Receptors Involvement. Parkinsons Dis. 2015;2015:431690. doi: 10.1155/2015/431690. Epub 2015 Mar 31.
- Escudero C, Casas S, Giuliani F, Bazzocchini V, Garcia S, Yunes R, Cabrera R. Allopregnanolone prevents memory impairment: effect on mRNA expression and enzymatic activity of hippocampal 3-alpha hydroxysteroid oxide-reductase. Brain Res Bull. 2012 Feb 10;87(2-3):280-5. doi: 10.1016/j.brainresbull.2011.11.019. Epub 2011 Dec 6. Erratum In: Brain Res Bull. 2012 Nov 1;89(3-4):150.
- Casas S, Garcia S, Cabrera R, Nanfaro F, Escudero C, Yunes R. Progesterone prevents depression-like behavior in a model of Parkinson's disease induced by 6-hydroxydopamine in male rats. Pharmacol Biochem Behav. 2011 Oct;99(4):614-8. doi: 10.1016/j.pbb.2011.06.012. Epub 2011 Jun 15.
- Casas S, Gonzalez Deniselle MC, Gargiulo-Monachelli GM, Perez AF, Tourreilles M, Mattiazzi M, Ojeda C, Lotero Polesel D, De Nicola AF. Neuroactive Steroids in Acute Ischemic Stroke: Association with Cognitive, Functional, and Neurological Outcomes. Horm Metab Res. 2017 Jan;49(1):16-22. doi: 10.1055/s-0042-119201. Epub 2016 Nov 3.
- Ghersi MS, Casas SM, Escudero C, Carlini VP, Buteler F, Cabrera RJ, Schioth HB, de Barioglio SR. Ghrelin inhibited serotonin release from hippocampal slices. Peptides. 2011 Nov;32(11):2367-71. doi: 10.1016/j.peptides.2011.07.015. Epub 2011 Jul 27.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2016年4月1日
一次修了 (実際)
2016年12月1日
研究の完了 (実際)
2016年12月1日
試験登録日
最初に提出
2017年8月2日
QC基準を満たした最初の提出物
2017年8月7日
最初の投稿 (実際)
2017年8月8日
学習記録の更新
投稿された最後の更新 (実際)
2017年8月8日
QC基準を満たした最後の更新が送信されました
2017年8月7日
最終確認日
2017年8月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
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