scholarly journals Ischemic Stroke, Glucocorticoids, and Remote Hippocampal Damage: A Translational Outlook and Implications for Modeling

2021 ◽  
Vol 15 ◽  
Author(s):  
Natalia V. Gulyaeva ◽  
Mikhail V. Onufriev ◽  
Yulia V. Moiseeva
Keyword(s):  
Ischemic Stroke ◽  
Emotional Disorders ◽  
Hpa Axis ◽  
Brain Dysfunction ◽  
Emotional Disturbances ◽  
Stress Axis ◽  
Hippocampal Damage ◽  
Post Stroke ◽  
Hippocampal Dysfunction ◽  
Patients At Risk

Progress in treating ischemic stroke (IS) and its delayed consequences has been frustratingly slow due to the insufficient knowledge on the mechanism. One important factor, the hypothalamic-pituitary-adrenocortical (HPA) axis is mostly neglected despite the fact that both clinical data and the results from rodent models of IS show that glucocorticoids, the hormones of this stress axis, are involved in IS-induced brain dysfunction. Though increased cortisol in IS is regarded as a biomarker of higher mortality and worse recovery prognosis, the detailed mechanisms of HPA axis dysfunction involvement in delayed post-stroke cognitive and emotional disorders remain obscure. In this review, we analyze IS-induced HPA axis alterations and supposed association of corticoid-dependent distant hippocampal damage to post-stroke brain disorders. A translationally important growing point in bridging the gap between IS pathogenesis and clinic is to investigate the involvement of the HPA axis disturbances and related hippocampal dysfunction at different stages of SI. Valid models that reproduce the state of the HPA axis in clinical cases of IS are needed, and this should be considered when planning pre-clinical research. In clinical studies of IS, it is useful to reinforce diagnostic and prognostic potential of cortisol and other HPA axis hormones. Finally, it is important to reveal IS patients with permanently disturbed HPA axis. Patients-at-risk with high cortisol prone to delayed remote hippocampal damage should be monitored since hippocampal dysfunction may be the basis for development of post-stroke cognitive and emotional disturbances, as well as epilepsy.

scholarly journals MEKANISME IMUNODEPRESI PASCASTROKE

2019 ◽  
Vol 36 (3) ◽  
Author(s):  
Al Rasyid
Keyword(s):  
Immune Response ◽  
Nervous System ◽  
Ischemic Stroke ◽  
Immune System ◽  
Immune Responses ◽  
Functional Outcome ◽  
Hpa Axis ◽  
Post Stroke ◽  
Cholinergic Pathway

  POST-STROKE IMMUNODEPRESSION MECHANISMSABSTRACTImmunodepression refers to a condition when immune system has reduced capacity to fulfill its functions therefore leading to infection. Infections develop frequently after stroke, and have been associated with poor clinical and functional outcome. Several studies show ischemic stroke, leads to impairment of immune responses, which increases susceptibility of an infection. This review analyzes the mechanisms of post-stroke immunodepression involving nervous system, such as adrenergic pathway, cholinergic pathway, or HPA axis, comprehensively based on recent clinical and experimental evidences. A better understanding of immune system modification after stroke could encourage further studies regarding immunomodulation therapy use in fighting infection.Keywords: Immune response, infection, post-stroke immunodepressionABSTRAKImunodepresi merupakan suatu kondisi saat sistem imun tidak dapat menjalankan perannya dengan baik sehingga dapat menimbulkan suatu infeksi. Infeksi sendiri merupakan komplikasi yang umum terjadi pascastroke, dihubungkan dengan luaran klinis dan fungsional yang buruk pada pasien stroke. Berbagai studi klinis menyimpulkan kondisi iskemik pada stroke menyebabkan gangguan pada respons imun sehingga menimbulkan kerentanan terhadap infeksi. Tulisan ini membahas mekanisme imunodepresi pascastroke terkait sistem saraf, baik jalur adrenergik, kolinergik, dan aksis HPA, secara komprehensif berbasis bukti klinis maupun eksperimental. Pemahaman konsep modifikasi sistem imun pascastroke dapat mendorong studi-studi lanjutan terkait penggunaan terapi imunomodulasi untuk melawan komplikasi infeksi.Kata kunci: Imunodepresi pascastroke, infeksi, respons imun

scholarly journals Correction of post-stroke cognitive and motor disorders

2020 ◽  
Vol 4 (9) ◽  
pp. 584-549
Author(s):  
A.V. Chugunov ◽  
◽  
L.I. Pyshkina ◽  
Z.Kh. Osmayeva ◽  
◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Emotional Disorders ◽  
Developed Countries ◽  
Motor Disorders ◽  
Good Tolerability ◽  
Post Stroke ◽  
Complex Process ◽  
Increased Risk ◽  
Post Stroke Depression ◽  
Treatment Onset

Ischemic stroke (IS) is one of the main causes of fatal income and disability in most developed countries. Disability due to IS is primarily caused by motor (paresis, ataxia), cognitive and emotional disorders. Post-stroke depression and dementia are associated not only with low compliance to rehabilitation measures and their low efficacy, but also with an increased risk of repeated episodes of acute brain and coronary ischemia, and mortality from cardiovascular diseases. Correction of post-stroke disorders is a complex process; its effectiveness is ensured by timely detection of disorders, early treatment onset, and combined use of medications and non-medications. The article discusses methods to the treatment of patients who have experienced IS, receiving choline alfoscerate. The results of drug administration in both acute and longterm IS were analyzed. Improvement of motor, cognitive and emotional functions was noted. Good tolerability of the drug and the possibility of its simultaneous use with other drugs were emphasized. KEYWORDS: ischemic stroke, post-stroke depression, post-stroke cognitive impairment, hemiparesis, neurometabolic drugs, choline alfoscerate, treatment, rehabilitation. FOR CITATION: Chugunov A.V., Pyshkina L.I., Osmayeva Z.Kh. Correction of post-stroke cognitive and motor disorders. Russian Medical Inquiry. 2020;4(9):584–589. DOI: 10.32364/2587-6821-2020-4-9-584-589.

LncRNAs a New Target for Post-Stroke Recovery

2020 ◽  
Vol 26 (26) ◽  
pp. 3115-3121
Author(s):  
Jun Yang ◽  
Jingjing Zhao ◽  
Xu Liu ◽  
Ruixia Zhu
Keyword(s):  
Ischemic Stroke ◽  
Microglial Activation ◽  
Vital Role ◽  
Stroke Recovery ◽  
Biological Processes ◽  
Current Development ◽  
Post Stroke ◽  
Cascade Processes ◽  
Non Coding Rnas ◽  
Neuron Injury

LncRNAs (long non-coding RNAs) are endogenous molecules, involved in complicated biological processes. Increasing evidence has shown that lncRNAs play a vital role in the post-stroke pathophysiology. Furthermore, several lncRNAs were reported to mediate ischemia cascade processes include apoptosis, bloodbrain barier breakdown, angiogenesis, microglial activation induced neuroinflammation which can cause neuron injury and influence neuron recovery after ischemic stroke. In our study, we first summarize current development about lncRNAs and post-stroke, focus on the regulatory roles of lncRNAs on pathophysiology after stroke. We also reviewed genetic variation in lncRNA associated with functional outcome after ischemic stroke. Additionally, lncRNA-based therapeutics offer promising strategies to decrease brain damage and promote neurological recovery following ischemic stroke. We believe that lncRNAs will become promising for the frontier strategies for IS and can open up a new path for the treatment of IS in the future.

Red Blood Cell Indices in Relation to Post-stroke Psychiatric Disorders: A Longitudinal Study in a Follow-up Stroke Clinic

2020 ◽  
Vol 17 (3) ◽  
pp. 218-223
Author(s):  
Haichao Wang ◽  
Li Gong ◽  
Xiaomei Xia ◽  
Qiong Dong ◽  
Aiping Jin ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Ischemic Stroke ◽  
Blood Cell ◽  
Cox Regression ◽  
Depression And Anxiety ◽  
Cox Regression Analysis ◽  
Post Stroke ◽  
Rbc Indices ◽  
Post Stroke Depression

Background: Depression and anxiety after stroke are common conditions that are likely to be neglected. Abnormal red blood cell (RBC) indices may be associated with neuropsychiatric disorders. However, the association of RBC indices with post-stroke depression (PSD) and poststroke anxiety (PSA) has not been sufficiently investigated. Methods: We aimed to investigate the trajectory of post-stroke depression and anxiety in our follow- up stroke clinic at 1, 3, and 6 months, and the association of RBC indices with these. One hundred and sixty-two patients with a new diagnosis of ischemic stroke were followed up at 1, 3, and 6 months, and underwent Patient Health Questionnaire-9 (PHQ-9) and the general anxiety disorder 7-item (GAD-7) questionnaire for evaluation of depression and anxiety, respectively. First, we used Kaplan-Meier analysis to investigate the accumulated incidences of post-stroke depression and post-stroke anxiety. Next, to explore the association of RBC indices with psychiatric disorders after an ischemic stroke attack, we adjusted for demographic and vascular risk factors using multivariate Cox regression analysis. Results: Of the 162 patients with new-onset of ischemic stroke, we found the accumulated incidence rates of PSD (1.2%, 17.9%, and 35.8%) and PSA (1.2%, 13.6%, and 15.4%) at 1, 3, and 6 months, respectively. The incident PSD and PSA increased 3 months after a stroke attack. Multivariate Cox regression analysis indicated independent positive associations between PSD risk and higher mean corpuscular volume (MCV) (OR=1.42, 95% CI=1.16-1.76), older age (OR=2.63, 95% CI=1.16-5.93), and a negative relationship between male sex (OR=0.95, 95% CI=0.91-0.99) and PSA. Conclusion: The risks of PSD and PSA increased substantially 3 months beyond stroke onset. Of the RBC indices, higher MCV, showed an independent positive association with PSD.

scholarly journals The Relationship of Psychiatric Symptoms with Performance-Based and Self-Reported Cognitive Function After Ischemic Stroke

2021 ◽  
pp. 1-13
Author(s):  
Elisabeth Kliem ◽  
Elise Gjestad ◽  
Truls Ryum ◽  
Alexander Olsen ◽  
Bente Thommessen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Executive Function ◽  
Depressive Symptoms ◽  
Cognitive Function ◽  
Psychiatric Symptoms ◽  
Post Stroke ◽  
Cognitive Difficulties ◽  
Memory And Attention ◽  
Relationship Of ◽  
The Relationship

Abstract Objective: Findings on the relationship of psychiatric symptoms with performance-based and self-reported cognitive function post-stroke are inconclusive. We aimed to (1) study the relation of depression and anxiety to performance-based cognitive function and (2) explore a broader spectrum of psychiatric symptoms and their association with performance-based versus self-reported cognitive function. Method: Individuals with supratentorial ischemic stroke performed neuropsychological examination 3 months after stroke. For primary analyses, composite scores for memory and attention/executive function were calculated based on selected neuropsychological tests, and the Hospital Anxiety and Depression Scale (HADS) was used. Psychiatric symptoms and self-reported cognitive function for secondary aims were assessed using the Symptom-Checklist-90 – Revised (SCL-90-R). Results: In a sample of 86 patients [mean (M) age: 64.6 ± 9.2; Mini-Mental State Examination (MMSE), 3–7 days post-stroke: M = 28.4 ± 1.7; National Institutes of Health Stroke Scale (NIHSS) after 3 months: M = 0.7 ± 1.6] depressive symptoms (HADS) were associated with poorer memory performance after controlling for age, sex, and education (p ≤ .01). In a subsample (n = 41; Age: M = 65.7 ± 8.1; MMSE: M = 28.4 ± 1.8; NIHSS: M = 1.0 ± 1.9), symptoms of phobic anxiety (SCL-90-R) were associated with poorer performance-based memory and attention/executive function, and symptoms of anxiety (SCL-90-R) with lower attention/executive function. Higher levels of self-reported cognitive difficulties were associated with higher scores in all psychiatric domains (p ≤ .05). Conclusion: Even in relatively well-functioning stroke patients, depressive symptoms are associated with poorer memory. The results also suggest that various psychiatric symptoms are more related to self-reported rather than to performance-based cognitive function. Screening for self-reported cognitive difficulties may not only help to identify patients with cognitive impairment, but also those who need psychological treatment.

scholarly journals Effects of long-term anti-seizure medication monotherapy on all-cause death in patients with post-stroke epilepsy: a nationwide population-based study in Taiwan

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chia-Yu Hsu ◽  
Chun-Yu Cheng ◽  
Jiann-Der Lee ◽  
Meng Lee ◽  
Bruce Ovbiagele
Keyword(s):  
Valproic Acid ◽  
Ischemic Stroke ◽  
Cox Regression ◽  
Population Based ◽  
Primary Diagnosis ◽  
Research Database ◽  
Post Stroke ◽  
Risk Of Death ◽  
Index Stroke

Abstract Objective We aim to compare the effect of long-term anti-seizure medication (ASM) monotherapy on the risk of death and new ischemic stroke in patients with post-stroke epilepsy (PSE). Patients and methods We identified all hospitalized patients (≥ 20 years) with a primary diagnosis of ischemic or hemorrhagic stroke from 2001 to 2012 using the National Health Insurance Research Database in Taiwan. The PSE cohort were defined as the stroke patients (1) who had no epilepsy and no ASMs use before the index stroke, and (2) who had epilepsy and ASMs use after 14 days from the stroke onset. The patients with PSE receiving ASM monotherapy were enrolled and were categorized into phenytoin, valproic acid, carbamazepine, and new ASM groups. We employed the Cox regression model to estimate the unadjusted and adjusted hazard ratios (HRs) with 95 % confidence intervals (CIs) of death and new ischemic stroke within 5 years across all groups, using the new ASM group as the reference. Results Of 6962 patients with PSE using ASM monotherapy, 3917 (56 %) were on phenytoin, 1623 (23 %) on valproic acid, 457 (7 %) on carbamazepine, and 965 (14 %) on new ASMs. After adjusting for confounders, compared with new ASM users, phenytoin users had a higher risk of death in 5 years (HR: 1.64; 95 % CI: 1.06–2.55). On the other hand, all ASM groups showed a similar risk of new ischemic stroke in 5 years. Conclusions Among patients with PSE on first-line monotherapy, compared to new ASMs, use of phenytoin was associated with a higher risk of death in 5 years.

scholarly journals Genetic variation at the IGF1 locus shows association with post-stroke outcome and to circulating IGF1

2013 ◽  
Vol 169 (6) ◽  
pp. 759-765 ◽  
Author(s):  
N David Åberg ◽  
Sandra Olsson ◽  
Daniel Åberg ◽  
Katarina Jood ◽  
Tara M Stanne ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Ischemic Stroke ◽  
Stroke Severity ◽  
Stroke Outcome ◽  
Nucleotide Polymorphisms ◽  
Post Stroke ◽  
Index Stroke ◽  
Genetic Impact ◽  
Major Allele ◽  
Community Controls

ObjectiveIn humans, serum IGF1 (s-IGF1) is associated with outcome after ischemic stroke (IS). Therefore variation at the IGF1 locus could also associate with both IS and s-IGF1. We investigated whether genetic variation at the IGF1 locus is associated with i) s-IGF1, ii) IS occurrence, iii) IS severity, and iv) post-stroke outcome.Design/methodsPatients (n=844; 66% males, mean age 56 years) and community controls (n=668) were included from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Post-stroke outcome was evaluated with the modified Rankin Scale at 3 and 24 months after index stroke, and baseline stroke severity with the Scandinavian Stroke Scale. s-IGF1 was determined in patients and after random selection in 40 of the controls.ResultsEleven single nucleotide polymorphisms (SNPs) were selected in the IGF1 gene. In healthy controls the major allele of rs7136446 was associated with higher s-IGF1, whereas in patients no such association was found. No SNP was associated with IS, nor with stroke severity. After multivariate correction for presence of diabetes, smoking, and hypertension, the major allele of rs7136446 was associated with favorable functional outcome 24-months post-stroke (odds ratio 1.46; 95% CI 1.09–1.96).ConclusionVariation in rs7136446 of the IGF1 gene associates with post-stroke outcome in relatively young IS patients. Also, rs7136446 associates with s-IGF1 in controls but not in IS, which indicates that IS perturbs a normal genetic impact on s-IGF1 levels.

Abstract TP274: Orosomucoid-1 Protein Increases Following Ischemic Stroke in the Brain and Periphery

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Hetal Mistry ◽  
Madeline Levy ◽  
Meaghan Roy-O'Reilly ◽  
Louise McCullough
Keyword(s):  
Sex Differences ◽  
Ischemic Stroke ◽  
Rna Sequencing ◽  
Multiple Testing ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Stroke Patients ◽  
Post Stroke ◽  
Protein Levels ◽  
The Brain

Background and Purpose: Orosomucoid-1 (ORM-1) is an abundant protein with important roles in inflammation and immunosuppression. We utilized RNA sequencing to measure mRNA levels in human ischemic stroke patients, with confirmation by serum ORM-1 protein measurements. A mouse model of ischemic stroke was then used to examine post-stroke changes in ORM-1 within the brain itself. Hypothesis: We tested the hypothesis that ORM-1 levels increase following ischemic stroke, with sex differences in protein dynamics over time. Methods: RNA sequencing was performed on whole blood from ischemic stroke patients (n=23) and controls (n=12), with Benjamini-Hochberg correction for multiple testing. Enzyme-linked immunosorbent assay was performed on serum from ischemic stroke patients (n=28) and controls (n=8), with analysis by T-test. For brain analysis, mice (n=14) were subjected to a 90-minute middle cerebral artery occlusion (MCAO) surgery and sacrificed 6 or 24 hours after stroke. Control mice underwent parallel “sham” surgery without occlusion. Western blotting was used to detect ORM-1 protein levels in whole brain, with analysis by two-way ANOVA. Results: RNA sequencing showed a 2.8-fold increase in human ORM-1 at 24 hours post-stroke (q=.0029), an increase also seen in serum ORM-1 protein levels (p=.011). Western blot analysis of mouse brain revealed that glycosylated (p=0.0003) and naive (p=0.0333) forms of ORM-1 were higher in female mice compared to males 6 hours post-stroke. Interestingly, ORM-1 levels were higher in the brains of stroke mice at 6 hours (p=.0483), while at 24 hours ORM-1 levels in stroke mice were lower than their sham counterparts (p=.0212). In both human and mouse data, no sex differences were seen in ORM-1 levels in the brain or periphery at 24 hours post-stroke. Conclusion: In conclusion, ORM-1 is a sexually dimorphic protein involved in the early (<24 hour) response to ischemic stroke. This research serves as an initial step in determining the mechanism of ORM-1 in the ischemic stroke response and its potential as a future therapeutic target for both sexes.

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