scholarly journals Neuroinflammatory Triangle Presenting Novel Pharmacological Targets for Ischemic Brain Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Zaib A. Shaheryar ◽  
Mahtab A. Khan ◽  
Ch. Sherjeel Adnan ◽  
Awais Ali Zaidi ◽  
Daniel Hänggi ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Intracellular Signaling ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Post Stroke ◽  
Intracellular Signaling Pathways ◽  
Pharmacological Targets ◽  
Specific Receptors ◽  
Ros Burst

Ischemic stroke is one of the leading causes of morbidity and mortality globally. Hundreds of clinical trials have proven ineffective in bringing forth a definitive and effective treatment for ischemic stroke, except a myopic class of thrombolytic drugs. That, too, has little to do with treating long-term post-stroke disabilities. These studies proposed diverse options to treat stroke, ranging from neurotropic interpolation to venting antioxidant activity, from blocking specific receptors to obstructing functional capacity of ion channels, and more recently the utilization of neuroprotective substances. However, state of the art knowledge suggests that more pragmatic focus in finding effective therapeutic remedy for stroke might be targeting intricate intracellular signaling pathways of the ‘neuroinflammatory triangle’: ROS burst, inflammatory cytokines, and BBB disruption. Experimental evidence reviewed here supports the notion that allowing neuroprotective mechanisms to advance, while limiting neuroinflammatory cascades, will help confine post-stroke damage and disabilities.

scholarly journals Post-Stroke Thalamic Syndrome (Review)

2019 ◽  
Vol 15 (5) ◽  
pp. 88-105
Author(s):  
S. A. Perepelitsa ◽  
T. A. Tumilovich ◽  
A. A. Shcherbakova
Keyword(s):  
Pain Management ◽  
Ischemic Brain Injury ◽  
Stroke Patients ◽  
Successful Management ◽  
Physiological Mechanisms ◽  
Ischemic Brain ◽  
Post Stroke ◽  
Comprehensive Rehabilitation

Pain management is a foreground task of physicians specializing in various disciplines. Special attention is paid to the issues of early comprehensive rehabilitation of post-stroke patients and prophylaxis of probable long-term complications related to injuries of different brain structures.Post-stroke thalamic syndrome is the most frequent multiform complication that requires multidisciplinary efforts. Understanding of the morbid physiology of pain thalamic syndrome is the cornerstone of successful management providing higher quality of patients’ life. Currently, profound changes have taken place in the prophylaxis, diagnosis, and management of post-stroke thalamic syndrome. This review highlights the most common types of pain experienced by patients after thalamic stroke, presents morbid physiological mechanisms of pain development depending on the location of ischemic brain injury, and discusses the issues of up-to-date management and rehabilitation of post-stroke thalamic syndrome patients.

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.

Abstract T MP18: In Vivo Expansion of Regulatory T cells with Interleukin-2/Interleukin-2-antibody Complex Protects against Transient Ischemic Stroke

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Haiyue Zhang ◽  
Peiying Li ◽  
Yanqin Gao ◽  
Jun Chen ◽  
Xiaoming Hu
Keyword(s):  
T Cells ◽  
Ischemic Stroke ◽  
Brain Injury ◽  
Regulatory T Cells ◽  
Interleukin 2 ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Treg Population ◽  
Antibody Complex

Background and Purpose: Our previous work documents the transfer of regulatory T cells (Tregs) in rodent models of ischemic stroke protects acute ischemic brain injury by regulating poststroke inflammatory response and thereby ameliorating BBB disruption. However, the low number of Tregs restricts the clinical feasibility of Treg transfer. Recently, in vivo expansion of Tregs with IL-2/IL-2-antibody complex (IL-2/IL-2Ab) was validated protective in autoimmune diseases model,renal ischemia reperfusion model and atherosclerosis. Here we investigate the beneficial effect of IL-2/IL-2Ab on ischemic stroke and decipher the underlying mechanisms. Methods: IL-2/IL-2Ab or isotype IgG was ip injected into C57/BL6 mice for 3 consecutive days. The mice are then subjected to 60-minute middle cerebral artery occlusion (MCAO) or sham operation. Brain infarction, inflammation and neurological performance was assessed up to 7 days after reperfusion. Results: Flow cytometry analysis reveals a marked increase of CD4+CD25+Foxp3+ Tregs in the blood, lymph nodes and spleens collected from IL-2/IL-2Ab-treated mice as compared to those from isotype-treated controls. Such Treg elevation could be observed since 3 days after IL-2/IL-2Ab injection and lasts until 7 days after MCAO. Immunochemistry staining confirms the increased number of Foxp3+ cells in the spleen at 3 days after MCAO in IL-2/IL-2Ab-treated mice. IL-2/IL-2Ab promotes function recovery up to 7 days after stroke, as revealed by significantly improved performance in corner test (n=6-9, ***p<0.001), rotarod test (n=8, **p<0.01), cylinder test (n=8, **p<0.01) and adhesive removal test (n=3, *p<0.05). Quantification of TTC staining and microtubule-associated protein (MAP2) staining shows reductions in brain infarct volume at 3 days (n=5-9,*p<0.05) and 7 days (n=7-9,*p<0.01), respectively, after MCAO. Meanwhile, we observed reduced infiltration of peripheral immune cells (CD3+ T cells, MPO+ neutrophils and F4/80+ macrophages) into the ischemic brain. Conclusions: Our finding suggests that IL-2/IL-2Ab treatment is a novel and clinical feasible immune therapy to expand Treg population in vivo, reduce post-stroke inflammatory responses and protect against ischemic brain injury.

Abstract TP319: Risk Factors of Post-stroke Epilepsy

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Tatyana Danilova ◽  
Dina Khasanova
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Functional Neuroimaging ◽  
Cerebral Arteries ◽  
Transcranial Doppler Sonography ◽  
Epileptic Seizures ◽  
Brain Lesions ◽  
Control Group ◽  
Ischemic Brain ◽  
Post Stroke

Purpose: The aim of the study was to identify the risk factors for seizures in patients with ischemic stroke using clinical, functional, neuroimaging research methods. Materials and methods: The results of the complex survey of 468 patients suffering from ischemic stroke (256 patients experienced epileptic seizures and 203 experienced no epileptic seizures) are presented. The diagnostic procedures included clinical evaluation, magnetic resonance imaging, electroencephalography, extracranial and transcranial Doppler sonography. In addition the assessment of the rate of sodium lithium countertransport (the marker of genetically determined on transport mechanisms of cell membranes) in patients with c ischemic stroke with the development of epileptic seizures and no seizures was carried out. Results: The focal seizures are the most common (92,5%). Cortical ischemic brain lesions prevailed in patients with seizures (81,1%), whereas in the control group cortex was affected in 38,9% patients (χ2=89.2, <0,001). Stenosis of cerebral arteries was more common in patients with epilepsy (82.3%) compared to patients without seizures (74.4%, <0.05). Reduced cerebrovascular reactivity (CVR) in vertebro-basilar basin was more frequently detected in patients with seizures (85.9%, p<0.001) compared to controls (71.6%). CVR < 10% was registered in 33.8% patients with seizures versus 13.4% controls (p<0.001). Patients with epileptic seizures showed cerebral perfusion reduction mostly in vertebro-basilar basin (85.9%) rather than in carotid basin (61.2%, p<0.001). Patients experienced epileptic seizures had high rates of sodium-lithium antitransport (> 346 μmol/liter cells x hour) more often than patients without epileptic seizures (52,6% and 35,5%, respectively, <0,05). Patients experienced epileptic seizures with high rates of sodium-lithium antitransport had a higher seizure frequency than patients with low rates of sodium-lithium antitransport. Conclusion: Thus, cortical ischemic brain lesions, significant stenosis of cerebral arteries, predominant perfusion reserve reduction in the posterior cerebral circulation, as well as a high rate of sodium lithium countertransport may be considered as risk factors for post-stroke epilepsy.

Abstract TP269: Lncrna-u90926 Aggravates Ischemic Brain Injury via Promoting Neutrophils Infiltration After Experimental Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Jian Chen ◽  
Yun Xu
Keyword(s):  
Ischemic Stroke ◽  
Brain Injury ◽  
Expression Level ◽  
Neurological Deficits ◽  
Neurological Injury ◽  
Experimental Stroke ◽  
Ischemic Brain Injury ◽  
Triphenyltetrazolium Chloride ◽  
Ischemic Brain ◽  
Severity Scores

Background: Long non-coding RNAs (LncRNAs) are expressed at high levels in the brain in a variety of neuropathologic conditions, including stroke. However, the potential role of LncRNAs in ischemic stroke-associated microglial biological function and neurological injury remains largely unknown. Methods: Oxygen-glucose deprivation and transient middle cerebral artery occlusion (MCAO) in C57BL/6 mice were used as in vitro and in vivo ischemic stroke models. Microarray analysis was performed to explore the overall expression level changes of LncRNAs. Real-time polymerase chain reaction (RT-qPCR) was used to detect expression level of LncU90926 in brain, plasma and microglia. ShRNA-LncU90926 in lentivirus and microglia specific Adeno-associated virus (AAV) were used to knockdown LncU90926 in vitro and in vivo separately. Infarct volumes and neurological impairments were assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining, Neurological Severity Scores (NSS), rotarod test and grip strength respectively. Immunofluorescence staining and flow cytometry were performed to detect the number of neutrophils recruited to brain. RT-qPCR was used to detect the level of chemokines (CXCL, CCL2) and inflammatory mediators associated with neutrophils (MPO, MMP3 and TIMP1). Results: (1). LncU90926 was markedly up-regulated in the infarcted brain and plasma after MCAO. Both MCAO and OGD treatment induced remarkable up-regulation of LncU90926 in microglia. (2). LncU90926 knockdown definitely attenuated brain infarct size and neurological deficits after ischemic stroke. (3). LncU90926 knockdown in microglia reduced the number of neutrophils recruited to brain, and CXCL1 and CCL2 were down-regulated in both MCAO and OGD models. LncU90926 knockdown also induced reduction of MPO, MMP3 and TIMP1 in the infarcted brain. Conclusions: LncU90926 was up-regulated in microglia after experimental stroke, and aggravates ischemic brain injury through facilitating neutrophils infiltration via up-regulating microglial chemokine.

scholarly journals Revisiting Stem Cell-Based Clinical Trials for Ischemic Stroke

2020 ◽  
Vol 12 ◽  
Author(s):  
Joy Q. He ◽  
Eric S. Sussman ◽  
Gary K. Steinberg
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Cell Types ◽  
Complex Problem ◽  
Review Article ◽  
Ischemic Brain ◽  
Cell Lineages ◽  
Ischemic Brain Tissue

Stroke is the leading cause of serious long-term disability, significantly reducing mobility in almost half of the affected patients aged 65 years and older. There are currently no proven neurorestorative treatments for chronic stroke. To address the complex problem of restoring function in ischemic brain tissue, stem cell transplantation-based therapies have emerged as potential restorative therapies. Aligning with the major cell types found within the ischemic brain, stem-cell-based clinical trials for ischemic stroke have fallen under three broad cell lineages: hematopoietic, mesenchymal, and neural. In this review article, we will discuss the scientific rationale for transplanting cells from each of these lineages and provide an overview of published and ongoing trials using this framework.

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