scholarly journals Astrocyte-secreted chordin-like 1 regulates spine density after ischemic stroke

2020 ◽  
Author(s):  
Elena Blanco-Suarez ◽  
Nicola J Allen
Keyword(s):  
Ischemic Stroke ◽  
Neuronal Survival ◽  
Clear Understanding ◽  
Spine Density ◽  
Morphological Alterations ◽  
Post Stroke ◽  
Infarct Area ◽  
Vital Functions ◽  
Underlying Mechanisms ◽  
Volume Characteristics

AbstractIschemic stroke occurs when the brain is deprived of blood flow, preventing cells from receiving nutrients necessary to perform basic vital functions. In the peri-infarct area neurons undergo an acute loss of dendritic spines along with morphological alterations, which ultimately modify synaptic plasticity and determine neuronal survival. Astrocytes have been shown to play protective or detrimental roles in neuronal survival post-stroke, depending on the specific stage, yet we lack a clear understanding of the underlying mechanisms triggered at these different time points. Recently chordin-like 1 (Chrdl1) was identified as an astrocyte-secreted protein that promotes synaptic maturation and limits experience-dependent plasticity in the mouse visual cortex, leading us to ask if Chrdl1 regulates spine density and recovery from stroke. Using photothrombosis to model ischemic stroke, we studied Chrdl1 KO mice during the acute and subacute phases post-stroke (1 and 7 days after injury, respectively) to assess the potential of Chrdl1 to regulate spine density, glial reactivity and injury volume, characteristics that are involved in functional recovery after ischemia. We find that the absence of Chrdl1 prevents ischemia-induced spine loss in the peri-infarct area, a feature that indicates an important role of astrocytes in recovery from ischemic stroke.

Abstract TMP121: Gender Differences in Functional Outcomes After Acute Ischemic Stroke: The Role of White Matter Structural Integrity

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Mark Etherton ◽  
Ona Wu ◽  
Pedro Cougo ◽  
Anne-Katrin Giese ◽  
Lisa Cloonan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Acute Ischemic Stroke ◽  
Functional Recovery ◽  
Stroke Subtype ◽  
Post Stroke ◽  
Significant Difference ◽  
Acute Infarct ◽  
Underlying Mechanisms ◽  
Microstructural Integrity

Background: Women are known to have worse post-stroke outcomes; however, the underlying mechanisms remain unclear. We evaluated sex-specific clinical and neuroimaging characteristics linked to cerebrovascular brain health in association with functional recovery after acute ischemic stroke (AIS). Methods: We reviewed 316 AIS patients with acute MRI (<48 hours from symptom onset) and modified Rankin scale score (mRS) assessed at 3-6 months post-stroke. Acute infarct volume on diffusion-weighted imaging (DWIv) and white matter hyperintensity volume (WMHv) on FLAIR sequences were determined using a validated semi-automated method. Mean diffusivity (MD) and fractional anisotropy (FA) of normal appearing white matter (NAWM) were derived from the contralesional hemisphere. Wilcoxon rank sum, Spearman correlation, and Fisher’s exact tests were used at p-value <0.05, as appropriate. Results: Women comprised 41.1% of this AIS cohort, and as compared to men, they were older (68 vs. 62.8 years, p = 0.002), had higher prevalence of atrial fibrillation (21.5% vs. 12.4%, p = 0.04), and less tobacco use (21.1% vs. 36.3%, p = 0.03). There was no statistically significant difference between men and women in admission stroke severity, TOAST stroke subtype distribution, DWIv or WMHv. However, women were significantly less likely to have a favorable outcome (mRS <2), as compared to men (53.7% vs. 68.5%, p = 0.01). Both FA (ρ -0.18, p=0.04) and MD (ρ 0.28, p=0.002) values in NAWM correlated with follow-up mRS in women, but only MD (ρ 0.26, p=0.0004) in men. Conclusion: Despite no differences in admission NIHSS, acute infarct size, WMH burden or stroke subtype, women with AIS had significantly worse post-stroke outcomes in our cohort. Our findings suggest that microstructural integrity, as assessed by NAWM diffusivity anisotropy measurements, may represent a neuroimaging correlate of worse outcomes in women. The correlation between markers of white matter microstructural integrity and long-term mRS provides insight into the underlying mechanisms of disease that may influence functional recovery after stroke.

Abstract 112: Recrudescence of Neurological Deficits After Stroke: Clinical-imaging Phenotype, Triggers and Risk Factors

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Aneesh B Singhal ◽  
Esen Saka ◽  
Scott B Silverman ◽  
Lee H Schwamm ◽  
Mehmet A Topcuoglu
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Vascular Lesion ◽  
Neurological Deficits ◽  
Imaging Features ◽  
Clinical Imaging ◽  
Stroke Registry ◽  
Post Stroke ◽  
Benzodiazepine Use ◽  
Underlying Mechanisms

Background: Re-emergence of prior stroke-related deficits or post-stroke recrudescence ( PSR ) has not been adequately studied. Methods: Using preliminary criteria for PSR (transient recurrence or worsening of residual post-stroke deficits; chronic brain infarct or hemorrhage but no acute vascular lesion on MRI including DWI; no severe ipsilateral cerebral artery stenosis; no evidence for seizure), we identified 153 patients (145 prior infarcts, 8 hypertensive ICH) with 164 admissions for PSR from 2000-2015. Clinical-imaging features of PSR were characterized. Triggers of PSR were identified by comparing PSR admissions to adjacent admissions without PSR (n=65). Risk factors for PSR were identified by comparing PSR cases to 1861 controls without PSR in our prospective institutional stroke registry. Results: PSR occurred 3.9±0.6y after stroke, lasted 18.4±20.4 hrs, and 69% resolved on Day 1. Mean age 67±16y, 60% women. Neuro-worsening was usually abrupt, mild, with motor-sensory or language dysfunction. No patient had isolated gaze paresis, hemianopia or neglect. During PSR the NIHSS worsened by mean 2.5±1.9 points; deficits were limited to a single subscale NIHSS item in 38%. The underlying chronic strokes were variably-sized, predominantly affected white-matter tracts, and 73% involved the MCA territory. Infection, hypotension, hyponatremia, insomnia/stress and benzodiazepine use were higher (p<0.05) during PSR as compared to adjacent admissions without PSR. As compared to the ischemic stroke registry controls, the subgroup of 145 cases with PSR after ischemic stroke had more women, African-American and Other races, diabetes, dyslipidemia, smoking, and more severe NIHSS scores at the time of index stroke (all p<0.05). The PSR group had more small-vessel infarcts and more strokes from “other definite” causes. Six patients with PSR received iv tPA without hemorrhagic complications. Conclusion: This detailed characterization of PSR should enable prompt diagnosis and distinguish PSR from mimics such as TIA, migraine, Todd’s paralysis, Uhthoff’s phenomenon, and others. This is the first large comprehensive study of PSR. Prospective studies are required to validate our proposed diagnostic criteria and decipher underlying mechanisms.

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 Congenital hypothyroidism impairs spine growth of dentate granule cells by downregulation of CaMKIV

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Qingying Tang ◽  
Shuxia Chen ◽  
Hui Wu ◽  
Honghua Song ◽  
Yongjun Wang ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Granule Cells ◽  
Spine Density ◽  
Drug Induced ◽  
Distinct Cell Type ◽  
Cognitive Behaviors ◽  
Dentate Granule Cells ◽  
Rat Pups ◽  
Cognitive Deficiency ◽  
Underlying Mechanisms

AbstractCongenital hypothyroidism (CH), a common neonatal endocrine disorder, can result in cognitive deficits if delay in diagnose and treatment. Dentate gyrus (DG) is the severely affected subregion of the hippocampus by the CH, where the dentate granule cells (DGCs) reside in. However, how CH impairs the cognitive function via affecting DGCs and the underlying mechanisms are not fully elucidated. In the present study, the CH model of rat pups was successfully established, and the aberrant dendrite growth of the DGCs and the impaired cognitive behaviors were observed in the offspring. Transcriptome analysis of hippocampal tissues following rat CH successfully identified that calcium/calmodulin-dependent protein kinase IV (CaMKIV) was the prominent regulator involved in mediating deficient growth of DGC dendrites. CaMKIV was shown to be dynamically regulated in the DG subregion of the rats following drug-induced CH. Interference of CaMKIV expression in the primary DGCs significantly reduced the spine density of dendrites, while addition of T3 to the primary DGCs isolated from CH pups could facilitate the spine growth of dendrites. Insights into relevant mechanisms revealed that CH-mediated CaMKIV deficiency resulted in the significant decrease of phosphorylated CREB in DGCs, in association with the abnormality of dendrites. Our results have provided a distinct cell type in hippocampus that is affected by CH, which would be beneficial for the treatment of CH-induced cognitive deficiency.

scholarly journals The neuropathological impact of COVID-19: a review

2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Ghadha Ibrahim Fouad
Keyword(s):  
Main Body ◽  
Respiratory Dysfunction ◽  
Behavior Understanding ◽  
Vital Functions ◽  
Global Issue ◽  
The Central Nervous System ◽  
Underlying Mechanisms ◽  
Neural Disorders ◽  
High Adaptation ◽  
Viral Outbreak

Abstract Background The Coronavirus disease 2019 (COVID-19) outbreak has become a challenging global issue after its emergence in December 2019. Due to the high adaptation of the virus, COVID-19 demonstrated a high transmission and infectivity potentials. Several studies demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induce deleterious neurological manifestations through interacting with the central nervous system (CNS). Main body The neuroinvasive potential of SARS-CoV-2 might contribute to its fatal behavior. Understanding the underlying mechanisms of this novel neuropathogen might contribute to the development of effective therapeutic strategies. The manifestations of neural damage in COVID-19 patients ranged from headache to severe encephalopathy and progression of preexisting neural disorders, it is speculated that neuroinvasion is strongly linked to the fatal respiratory dysfunction. The underlying neuropathological impact of emerging pneumonia (COVID-19) is still unclear. Conclusion This review demonstrated the urgent need to understand the neuropathology of COVID-19, to manage the current borderless viral outbreak of SARS-CoV-2 and its comorbidities. Moreover, SARS-CoV-2 could be regarded as an opportunistic neuropathogen that affects several vital functions in the human body.

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 Activation of Adenosine A1 Receptor in Ischemic Stroke: Neuroprotection by Tetrahydroxy Stilbene Glycoside as an Agonist

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1112
Author(s):  
Lingyu Ruan ◽  
Guanghui Li ◽  
Wenlong Zhao ◽  
Huihui Meng ◽  
Qi Zheng ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Glutamate Release ◽  
Chinese Herb ◽  
Adenosine A1 Receptor ◽  
Polygonum Multiflorum ◽  
Stroke Treatment ◽  
Cardiovascular Side Effects ◽  
Adenosine A1 ◽  
A1 Receptor ◽  
Underlying Mechanisms

Ischemic stroke is the main cause of death/disability, posing a great menace to human health. Though efforts to search for therapeutic drugs are ongoing, few of them have succeeded. Adenosine A1 receptor (A1R) activation could ameliorate ischemic injury, representing a very tempting target for stroke treatment. Tetrahydroxy stilbene glycoside (TSG), a potent antioxidant from the well-known Chinese herb Polygonum multiflorum Thunb., has been reported to have notable neuroprotective activities but the underlying mechanisms are elusive. This study investigated the mechanism of TSG focusing on A1R. TSG markedly decreased mortality, neurological deficit score, cerebral infarct size and brain water content of MCAO rats, and ameliorated the disorders in purine metabolism, energy metabolism and antioxidative defense system. TSG helped the survival of SH-SY5Y cells in OGD/R by alleviating oxidative stress and glutamate release, and by maintaining calcium homeostasis. TSG effects were abolished by A1R antagonist DPCPX. Docking and binding assays confirmed the binding of TSG with A1R. In addition, TSG upregulated the A1R level lowered by MCAO and OGD/R. The downstream signals of A1R activation, ERK1/2, HIF-1α and NF-κB contributed to the neuroprotection of TSG. Moreover, void of “well-known” cardiovascular side effects of classical A1R agonists, TSG showcased its great potential for stroke treatment.

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.

Sign in / Sign up

Export Citation Format

Share Document