Therapy In Ischemic Stroke Patients Research Articles

Building evidence on safety of endovascular thrombectomy for patients under anticoagulation with vitamin K antagonists.

A recent study by Brian Mac Grory and colleagues investigated the safety of endovascular thrombectomy (EVT) among patients under vitamin K antagonists (VKAs) use within 7 days prior to hospital admission. Through this retrospective, observational cohort study, they found prior VKA use did not increase the risk of symptomatic intracranial hemorrhage (sICH) overall. However, recent VKA use with a presenting international normalized ratio (INR) > 1.7 was associated with a significantly increased risk of sICH. Future large-scale randomized controlled trials should be conducted to further clarify the effects and feasibility of EVT therapy in ischemic stroke patients under anticoagulation.

Efficacy and safety of stem cells in the treatment of ischemic stroke: A meta-analysis.

Stem cell therapy on ischemic stroke has long been studied using animal experiments. The efficacy and safety of this treatment in ischemic stroke patients remain uncertain. We searched for all clinical randomized controlled trials published before October 2023, on PubMed, EMBASE, and the Cochrane Library using predetermined search terms, and performed a meta-analysis of the efficacy of stem cell therapy in ischemic stroke patients. 13 studies that included 592 ischemic stroke patients were reviewed. The mRS (MD -0.32, 95% CI -0.64 to 0.00, I2 = 63%, P = .05), NIHSS (MD -1.63, 95% CI -2.69 to -0.57, I2 = 58%, P = .003), and BI (MD 14.22, 95% CI 3.95-24.48, I2 = 43%, P = .007) showed effective stem cell therapy. The mortality (OR 0.42, 95% CI 0.23-0.79, I2 = 0%, P = .007) showed improved prognosis and reduce mortality with stem cell therapy. Stem cell therapy reduces mortality and improves the neurological prognosis of ischemic stroke patients. However, due to the different types of stem cells used and the limited data in the reported studies, the safety of clinical applications of stem cells in patients with ischemic stroke must be carefully evaluated. Future randomized controlled trials with large sample sizes from controlled cell sources are warranted to validate this finding.

Risk of intracranial hemorrhage in patients using anticoagulant therapy for atrial fibrillation after cerebral microbleeds combined with acute ischemic stroke: a meta-analysis.

To evaluate intracerebral hemorrhage (ICH) risk in patients with ischemic stroke (IS) and cerebral microbleeds (CMBs) undergoing anticoagulation therapy for non-valvular atrial fibrillation (AF). We conducted a comprehensive search across multiple databases, including Embase, PubMed, Cochrane, UpToDate, Scopus, WOS, and SinoMed. The search covered observational literature published from each database inception until February 1, 2023. We analyzed the prevalence of CMBs during the follow-up period, compared future ICH risk between patients with and without baseline CMBs (CMBs presence/absence, ≧5 CMBs), and examined factors influencing ICH occurrence in patients with CMBs. Also studied recurrent stroke during anticoagulation therapy, the risk of future ICH when white matter hyperintensity (WMH) and CMBs coexist, and the effects of anticoagulants vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) on future ICH. We included 7 articles involving 5,134 participants. The incidence of CMBs was 24%; baseline CMBs were associated with an increased ICH risk compared to patients without CMBs. ICH-risk was more significant in patients with baseline ≥5 CMBs. After anticoagulant therapy, ICH risk was higher than that of recurrent IS. The risk of future ICH was significantly increased with anticoagulant VKAs compared with NOAC. Anticoagulant therapy for ischemic stroke patients with non-valvular AF and CMBs increases future ICH risk. Discontinuing anticoagulation due to ICH risk should be avoided. NOACs are safe and effective for patients with CMBs and IS.

Exosome-like nanovesicles derived from Momordica charantia ameliorate delayed t-PA thrombolysis-induced hemorrhagic transformation by inhibiting the ONOO−/HMGB1/MMP-9 pathway

Hemorrhagic transformation (HT) and restrictive therapeutic time window are significant limitations of delayed t-PA (tissue-type plasminogen activator) thrombolytic therapy in ischemic stroke patients. Plant Momordica charantia-derived exosome-like nanovesicles (MC-ELNs) can protect the blood–brain barrier (BBB) and inhibit neuronal apoptosis in stroke rats by inhibiting matrix metalloproteinase 9(MMP-9) expression. This study explored the therapeutic function and underlying mechanisms of MC-ELNs in treating HT. In delayed t-PA-treated ischemia-reperfusion rats, MC-ELNs significantly reduced mortality, HT, and cell apoptosis; MC-ELNs improved neurological function and BBB's integrity. MC-ELNs reduced ONOO− and MMP-9 expression and inhibited the release of HMGB1 from intracellular to extracellular in vivo and in vitro. ONOO− donor SIN-1 directly induced extracellular secretion of HMGB1, MC-ELNs and FeTmPyP (ONOO− decomposition catalyst, PDC) significantly reduced the expression of HMGB1 and inhibited MMP-9 activation in vitro. These findings indicate that MC-ELNs could protect BBB integrity and improve t-PA-induced HT by inhibiting the ONOO−/HMGB1/MMP-9 pathway.

Gender Differences in Response to Statin Therapy in Ischemic Stroke Patients With SLCO1B1 388A>G Polymorphism: A Clinical Study

Background: Statins are widely used for the medical management of vascular conditions, including ischemic stroke. However, genetic factors and polymorphisms, including SLCO1B1 388A>G single-nucleotide polymorphism (SNP), have shown significant effects in response to statin therapy. To the best of our knowledge, gender-gene interaction in response to statin therapy, affected by the SLCO1B1 388 A>G SNP, has not been investigated yet. The current study describes the therapeutic outcomes of this variation in terms of clinical evaluations and laboratory parameters. Methods: Seventy patients diagnosed with acute ischemic stroke were recruited for this study. Blood samples were collected. The SLCO1B1 388A>G gene was genotyped using a polymerase chain reaction-restriction fragment length polymorphism method, and the three possible polymorphisms (388GG, 388GA, and 388AA) were detected accordingly. Statin treatment was prescribed at a dose of 40 mg of Atorvastatin or 20 mg of Rosuvastatin daily. Laboratory assessments, including a lipid profile, liver function tests, and lactate dehydrogenase, as well as clinical evaluations, including scores of stroke severity, were obtained at baseline and after a three-month follow-up. Results: Iranian ischemic stroke patients showed all three possible polymorphisms, including 30 patients with AA, 28 patients with AG, and 12 patients with GG. Significant SNP variations and gender-gene interactions for most measures of the lipid profile and some clinical trends were found in such a manner that the GG genotype was associated with relevant resistance to statin treatment, while the AA genotype, particularly in male patients, was associated with more response to statin treatment. Conclusion: This investigation adds influential gender differences to the previously reported SLCO1B1 388A>G SNP-induced variations of statin therapeutic response in stroke patients.

Literature Review: Drug Therapy in Ischemic Stroke Patients

Background: Ischemic stroke is the foremost common cause of stroke around the world, bookkeeping for 10 times more strokes than hemorrhagic strokes in higher pay nations. There are proof accessible for each antiplatelet sedate utilized in the treatment of ischemic stroke. The advertised recommendations for elective restorative choices when confronted with repetitive stroke. Aim: To know the use of antiplatelet in ischemic stroke patients. Method: This study used a systematic review that searched using the keyword Antiplatelet and Ischemic Stroke in Google Scholar, Crossref, and PubMed. Recent studies in English published in 2012-2022. Result: After the final screening, the author analyzed 4 articles that were published after the year 2012. Conclusion: In spite of the fact that great proof exists for the utilization of certain antiplatelet operators for postischemic stroke, there are significant openings for future investigation to examine personalized treatments. These incorporate screening patients for platelet polymorphisms that bestow antiplatelet resistance and for randomized trials counting more racially different populations.

Abstract 81: Shear-activated Nanoparticle Aggregates Containing Nitroglycerin Selectively Increase Collateral Perfusion During Experimental Ischemic Stroke

Introduction: Leptomeningeal collateral flow is a strong predictor of stroke outcome. Enhancing collateral flow is an appealing therapeutic approach. However, previous attempts to enhance collateral flow with vasodilators have failed, due to systemic hypotension and cerebrovascular steal from the penumbra. We have shown that during experimental stroke collaterals have fluid shear stress that is 3-7 times higher (100 dyne/cm 2 ) than other blood vessels. This unique feature of collateral vessels provides a way to selectively enhance flow, using nanoparticle aggregates loaded with nitroglycerin (NG-NPAs), that only release drug in areas of high shear stress (≥ 100 dyne/cm 2 ). Hypothesis: Shear-activated NG-NPAs will selectively enhance collateral perfusion and improve stroke outcome. Methods: Proximal occlusion of the middle cerebral artery (MCAo) was induced for 70 min in male Spontaneously Hypertensive Rats. Changes in cerebral blood flow in the collateral-supplied ischemic MCA territory, and in the contralateral homotypic region were measured by laser speckle contrast imaging. Animals were randomized to receive I.V. infusion of blank-NPA (B-NPA, control, 4mg in 2ml of saline, n=7) or NG-NPA (50μg NG in 4 mg NPA = 4μg/kg/min of NG, n=7), commencing 25 minutes after MCAo, until reperfusion. Infarct volume was measured at 24 h. Results: NG-NPA significantly increased collateral perfusion by 44% vs. 11% for B-NPA at 40 minutes post-infusion (p=0.026), without altering perfusion in the contralateral region (NG-NPA: +19%, B-NPA: +13% of pre-infusion baseline, p=0.99) and without reducing blood pressure (NG-NPA: 161 mmHg, B-NPA: 163 mmHg, p=0.99). NG-NPA significantly reduced infarct volume at 24 h (NG-NPA: 70 mm 3 , B-NPA: 121 mm 3 , p=0.005). Better collateral perfusion was correlated with smaller infarct volume (R 2 = 0.44, p=0.012). Conclusion: Shear-activated NG-NPA selectively enhanced collateral perfusion to penumbral tissue without inducing systemic side effects, which resulted in smaller infarcts in this model. Given the known importance of collateral flow, shear-activated NG-NPA show great promise as a potential therapy for ischemic stroke patients, both pre-reperfusion therapy and in those unsuitable for such therapies.

Atrial CARdiac Magnetic resonance imaging in patients with embolic stroke of unknown source without documented Atrial Fibrillation (CARM-AF): Study design and clinical protocol.

BackgroundInitiation of anticoagulation therapy in ischemic stroke patients is contingent on a clinical diagnosis of atrial fibrillation (AF). Results from previous studies suggest thromboembolic risk may predate clinical manifestations of AF. Early identification of this cohort of patients may allow early initiation of anticoagulation and reduce the risk of secondary stroke.ObjectiveThis study aims to produce a substrate-based predictive model using cardiac magnetic resonance imaging (CMR) and baseline noninvasive electrocardiographic investigations to improve the identification of patients at risk of future thromboembolism.MethodsCARM-AF is a prospective, multicenter, observational cohort study. Ninety-two patients will be recruited following an embolic stroke of unknown source (ESUS) and undergo atrial CMR followed by insertion of an implantable loop recorder (ILR) as per routine clinical care within 3 months of index stroke. Remote ILR follow-up will be used to allocate patients to a study or control group determined by the presence or absence of AF as defined by ILR monitoring.ResultsBaseline data collection, noninvasive electrocardiographic data analysis, and imaging postprocessing will be performed at the time of enrollment. Primary analysis will be performed following 12 months of continuous ILR monitoring, with interim and delayed analyses performed at 6 months and 2 and 3 years, respectively.ConclusionThe CARM-AF Study will use atrial structural and electrocardiographic metrics to identify patients with AF, or at high risk of developing AF, who may benefit from early initiation of anticoagulation.

Associations of CYP2C19 and F2R genetic polymorphisms with platelet reactivity in Chinese ischemic stroke patients receiving clopidogrel therapy.

Genetic variation has been considered a major contributor to the high variability in the response to dual antiplatelet therapy in patients with acute ischemic stroke or transient ischemic attack. Recently, incidences of ischemic stroke are increasing rapidly in China. We aimed to evaluate the influence of potential determinants on the response of antiplatelet therapy and adverse events in Chinese ischemic stroke patients receiving clopidogrel-aspirin treatment. Based on the clopidogrel drug response pathway and the coagulation and anticoagulation function, we systematically selected 34 genetic polymorphisms in 12 candidate genes. Three hundred and eight patients were divided into 2 groups according to their degree of inhibition of platelet aggregation. Multivariate analysis was then performed to assess the influence of demographic, clinical and genetic factors on platelet reactivity in Chinese ischemic stroke patients. We found that polymorphisms in CYP2C19 and F2R genes were still significantly associated with platelet reactivity in Chinese ischemic stroke patients (P = 0.037 and 0.015). The newly identified rs168753 in F2R gene may influence the efficacy to clopidogrel-aspirin therapy for ischemic stroke patients. We also found that ischemic stroke patients with low level of inhibition of platelet aggregation had higher risk of recurrent ischemic events (P = 0.001). Together, these results emphasized the necessity of genotype-directed antiplatelet therapy and facilitated to minimize adverse ischemic events.

Mechanisms of Preconditioning Exercise-Induced Neurovascular Protection in Stroke.

Ischemic stroke is a leading cause of death and disability. Tissue plasminogen activator is the only U.S. Food and Drug Administration approved thrombolytic therapy for ischemic stroke patients till date. However, its use is limited due to increased risk of bleeding and narrow therapeutic window. Most of the preclinically tested pharmacological agents failed to be translated to the clinic. This drives the need for alternative therapeutic approaches that not only provide enhanced neuroprotection, but also reduce the risk of stroke. Physical exercise is a sort of preconditioning that provides the body with brief ischemic episodes that can protect the body from subsequent severe ischemic attacks like stroke. Physical exercise is known to improve cardiovascular health. However, its role in providing neuroprotection in stroke is not clear. Clinical observational studies showed a correlation between regular physical exercise and reduced risk and severity of ischemic stroke and better outcomes after stroke. However, the underlying mechanisms through which prestroke exercise can reduce the stroke injury and improve the outcomes are not completely understood. The purpose of this review is to: demonstrate the impact of exercise on stroke outcomes and show the potential role of exercise in stroke prevention and recovery; uncover the underlying mechanisms through which exercise reduces the neurovascular injury and improves stroke outcomes aiming to develop novel therapeutic approaches.

Safety and Outcomes of Intravenous Thrombolytic Therapy in Ischemic Stroke Patients with COVID-19: CASCADE Initiative

BackgroundThere is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19. MethodsThis multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes. ResultsA total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054). ConclusionIV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.

Prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup.

To mitigate the incidence of recurrent stroke inpatients, dual antiplatelet therapy comprising aspirin andclopidogrel is usually administered. Clopidogrel is a prodrug and its bioactivation is catalyzed by cytochrome P450 (CYP)2C19. The main objective of this work was to determine the prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and assess the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup. This prospective (2018-2019) study was conducted on 256 patients (age 61±12.5) clinically diagnosed with ischemic stroke who were genotyped using Spartan RX CYP2C19 assay. From the total patient group (256), upon admission, 210 patients were prescribed either aspirin, clopidogrel or dual antiplatelet therapy. Of the 27 patients with the CYP2C19*2 allele who were prescribed clopidogrel (18) or dual antiplatelet therapy (9), only 21 patients could be followed up for a period of six months post stroke event, in addition to 21 age- and sex-matched patients with the normal allele. The CYP2C19*2 allele carriers had a statistically significant increased risk of recurrent stroke compared to patients carrying the normal allele. This study shows the suitability of using genotyping to guide antiplatelet therapy in ischemic stroke patients in a clinical setting.

Prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup.

To mitigate the incidence of recurrent stroke inpatients, dual antiplatelet therapy comprising aspirin andclopidogrel is usually administered. Clopidogrel is a prodrug and its bioactivation is catalyzed by cytochrome P450 (CYP)2C19. The main objective of this work was to determine the prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and assess the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup. This prospective (2018-2019) study was conducted on 256 patients (age 61±12.5) clinically diagnosed with ischemic stroke who were genotyped using Spartan RX CYP2C19 assay. From the total patient group (256), upon admission, 210 patients were prescribed either aspirin, clopidogrel or dual antiplatelet therapy. Of the 27 patients with the CYP2C19*2 allele who were prescribed clopidogrel (18) or dual antiplatelet therapy (9), only 21 patients could be followed up for a period of six months post stroke event, in addition to 21 age- and sex-matched patients with the normal allele. The CYP2C19*2 allele carriers had a statistically significant increased risk of recurrent stroke compared to patients carrying the normal allele. This study shows the suitability of using genotyping to guide antiplatelet therapy in ischemic stroke patients in a clinical setting.

Neuromodulatory Effect of Sensorimotor Network Functional Connectivity of Temporal Three-Needle Therapy for Ischemic Stroke Patients with Motor Dysfunction: Study Protocol for a Randomized, Patient-Assessor Blind, Controlled, Neuroimaging Trial

Background The clinical efficacy of temporal three-needle therapy for stroke dysfunction has been previously demonstrated in China. However, the central mechanism of temporal three-needle therapy remains unclear. Temporal three-needle projects the sensory cortex and the motor cortex, which may impact the cortex function. Current studies seldom focus on it. Hence, according to the “scalp-cortex corresponding theory,” the underlying mechanism of temporal three-needle remains a domain for further research. Methods This trial is designed to provide objective and visual evidence for the neuromodulatory effect and neuroimaging mechanism of temporal three-needle therapy for stroke patients. This ongoing study is a prospective, randomized, controlled, patient-assessor blind, single-center, neuroimaging trial involving two-parallel patient groups and a healthy control group. Forty eligible patients will be recruited from Shenzhen Nanshan District People's Hospital and randomized into either the experimental group or the control group. Twenty healthy volunteers will be recruited in the healthy control group and undergo baseline magnetic resonance imaging scans without any intervention. Patients in the control group will receive acupuncture at Dingnieqianxiexian (MS6), in addition to basic medicine and rehabilitative treatments. Patients in the experimental group will receive temporal three-needle therapy plus basic medicine and rehabilitative treatments 5 days per week, 10 sessions over two consecutive weeks. The primary outcome is resting-state functional connectivity, and the secondary outcomes are regional homogeneity, amplitude of low-frequency fluctuations, Fugl–Meyer assessment of the upper limb, and modified Barthel Index. All outcome measures will be assessed at baseline and after 2 weeks of intervention. Discussion. The results will explore the neuromodulatory effects and illustrate the central mechanism of temporal three-needle treatment from the network-level viewpoint of sensorimotor network functional plasticity and promote widespread application in real-world practice. This trial was registered at Chinese Clinical Trial Registry on 14 March 2018 with ChiCTR1800015209.

Diabetes Mellitus/Poststroke Hyperglycemia: a Detrimental Factor for tPA Thrombolytic Stroke Therapy.

Intravenous administration of tissue-type plasminogen activator (IV tPA) therapy has long been considered a mainstay in ischemic stroke management. However, patients respond to IV tPA therapy unequally with some subsets of patients having worsened outcomes after treatment. In particular, diabetes mellitus (DM) is recognized as a clinically important vascular comorbidity that leads to lower recanalization rates and increased risks of hemorrhagic transformation (HT). In this short-review, we summarize the recent advances in understanding of the underlying mechanisms involved in post-IV tPA worsening of outcome in diabetic stroke. Potential pathologic factors that are related to the suboptimal tPA recanalization in diabetic stroke include higher plasma plasminogen activator inhibitor (PAI)-1 level, diabetic atherogenic vascular damage, glycation of the tPA receptor annexin A2, and alterations in fibrin clot density. While factors contributing to the exacerbation of HT in diabetic stroke include hyperglycemia, vascular oxidative stress, and inflammation, tPA neurovascular toxicity and imbalance in extracellular proteolysis are discussed. Besides, impaired collaterals in DM also compromise the efficacy of IV tPA therapy. Additionally, several tPA combination approaches developed from experimental studies that may help to optimize IV tPA therapy are also briefly summarized. In summary, more research efforts are needed to improve the safety and efficacy of IV tPA therapy in ischemic stroke patients with DM/poststroke hyperglycemia.

Thrombolytic therapy in ischemic stroke patients with pre-stroke depression in the telestroke vs non-telestroke

Background and PurposeThrombolysis therapy remains the gold standard in acute ischemic stroke treatment, and rates of treatment with rtPA in ischemic stroke patients with comorbid depression has yet to be fully investigated. This study aims to examine clinical risk factors associated with inclusion or exclusion for rtPA in acute ischemic stroke populations with pre-stroke depression in the telestroke versus a non-telestroke setting. MethodsWe collected retrospective data from a regional stroke registry for pre-stroke depressed ischemic stroke patients from January 2010 to June 2016. Logistic regression was used to determine demographic and baseline clinical risk factors associated with inclusion and exclusion from rtPA. Results. In the adjusted analysis, increasing age (OR = 1.064, 95% CI, 1.006-1.125, P = 0.029), improved ambulation (OR = 3.513, 95% CI, (0.855–14.436, P = 0.018) and sleep apnea (OR = 4.458, 95% CI, 0.731–27.182, P = 0.05) were associated with inclusion for rtPA, while Caucasian race (OR = 0.119, 95% CI, 0.0168–0.908, P = 0.040), systolic blood pressure (OR = 0.945, 95% CI, 0.906–0.985, P = 0.008), and direct admission (OR = 0.028, 95% CI, 0.003–0.317, P = 0.004) were associated with exclusion from rtPA. In the telestroke setting, INR (OR = 1.016, 95% CI, 0–5.393, P = 0.163) was not significantly associated with rtPA inclusion or exclusion. ConclusionIdentifying contraindicators associated with exclusion from rtPA is significant to improve the use thrombolytic therapy in the telestroke and non telestroke settings.

Characterization of the TNF and IL-1 systems in human brain and blood after ischemic stroke

Preclinical and clinical proof-of-concept studies have suggested the effectiveness of pharmacological modulation of inflammatory cytokines in ischemic stroke. Experimental evidence shows that targeting tumor necrosis factor (TNF) and interleukin (IL)-1 holds promise, and these cytokines are considered prime targets in the development of new stroke therapies. So far, however, information on the cellular expression of TNF and IL-1 in the human ischemic brain is sparse.We studied 14 cases of human post-mortem ischemic stroke, representing 21 specimens of infarcts aged 1 to > 8 days. We characterized glial and leukocyte reactions in the infarct/peri-infarct (I/PI) and normal-appearing tissue (NAT) and the cellular location of TNF, TNF receptor (TNFR)1 and TNFR2, IL-1α, IL-1β, and IL-1 receptor antagonist (IL-1Ra). The immunohistochemically stained tissue sections received a score reflecting the number of immunoreactive cells and the intensity of the immunoreactivity (IR) in individual cells where 0 = no immunoreactive cells, 1 = many intermediately to strongly immunoreactive cells, and 2 = numerous and intensively immunoreactive cells. Additionally, we measured blood TNF, TNFR, and IL-1 levels in surviving ischemic stroke patients within the first 8 h and again at 72 h after symptom onset and compared levels to healthy controls.We observed IL-1α and IL-1β IR in neurons, glia, and macrophages in all specimens. IL-1Ra IR was found in glia, in addition to macrophages. TNF IR was initially found in neurons located in I/PI and NAT but increased in glia in older infarcts. TNF IR increased in macrophages in all specimens. TNFR1 IR was found in neurons and glia and macrophages, while TNFR2 was expressed only by glia in I/PI and NAT, and by macrophages in I/PI. Our results suggest that TNF and IL-1 are expressed by subsets of cells and that TNFR2 is expressed in areas with increased astrocytic reactivity. In ischemic stroke patients, we demonstrate that plasma TNFR1 and TNFR2 levels increased in the acute phase after symptom onset compared to healthy controls, whereas TNF, IL-1α, IL-1β, and IL-1Ra did not change.Our findings of increased brain cytokines and plasma TNFR1 and TNFR2 support the hypothesis that targeting post-stroke inflammation could be a promising add-on therapy in ischemic stroke patients.

The Impact of Loading Dose on Outcome in Stroke Patients Receiving Low-Dose Tissue Plasminogen Activator Thrombolytic Therapy.

BackgroundIntravenous tissue plasminogen activator (tPA) (0.9 mg/kg, maximum 90 mg) with a bolus of 10% of the total dose given within 1–2 mins is the standard therapy for patients receiving thrombolytic therapy. Low-dose (0.6 mg/kg) tPA is also approved for thrombolytic therapy for ischemic stroke patients. Low-dose tPA is associated with a low bolus dose. It is unknown whether increasing the bolus dose in patients receiving low-dose tPA thrombolysis may improve outcomes or increase the risk of hemorrhagic transformation (HT).AimThis study investigated the impact of the bolus dose on the outcome in ischemic stroke patients receiving low-dose tPA thrombolytic therapy.MethodsIn this retrospective, observational study, we enrolled 214 ischemic stroke patients receiving low-dose tPA thrombolytic therapy. Of these 214 patients, 107 patients received 10% of the total dose as a bolus dose, and 107 patients received 15% of the total dose as a bolus dose. The National Institutes of Health Stroke Score (NIHSS) were evaluated before tPA infusion, 24 h after thrombolytic therapy, and at discharge. Stroke severity was categorized as mild (0–5), moderate (6–14), severe (15–24), or very severe (≥25). Neurological improvement (NI) was defined as an improvement of 6 or more points in the NIHSS, and no response (NR) was defined as an increase in the NIHSS of ≤4 points or a decrease ≤6 points. Neurological deterioration (ND) was defined as an increase in the NIHSS >4 points. A good outcome was defined as a modified Ranking Score (mRS) of 0 or 1. We compared the NI, NR, and ND rates at 24 hrs after thrombolytic therapy and discharge between the 15% and 10% bolus dose groups.ResultsIn patients with mild and moderate stroke, there was no significant difference in the NI, NR, ND, and HT rates and 6-month outcomes between the 15% and 10% bolus groups. In patients with severe and very severe stroke, outcomes at 6 months were significantly better in the 15% bolus group than in the 10% bolus group. The factors affecting the outcomes of severe and very severe stroke patients are hypertension and bolus dose.ConclusionIn severe and very severe stroke patients receiving low-dose tPA thrombolytic therapy, a bolus dose of 15% of the total dose can improve outcomes.

High-flow Nasal Cannula Oxygen Therapy for Ischemic Stroke Patients With Dysphagia and Obstructive Sleep Apnea

High-flow Nasal Cannula Oxygen Therapy for Ischemic Stroke Patients With Dysphagia and Obstructive Sleep Apnea

From the Lab to Patients: a Systematic Review and Meta-Analysis of Mesenchymal Stem Cell Therapy for Stroke.

There may be the potential to improve stroke recovery with mesenchymal stem cells (MSCs); however, questions about the efficacy and safety of this treatment remain. To address these issues and inform future studies, we performed a preclinical and clinical systematic review of MSC therapy for subacute and chronic ischemic stroke. MEDLINE, Embase, the Cochrane Register of Controlled Trials, and PubMed were searched. For the clinical review, interventional and observational studies of MSC therapy in ischemic stroke patients were included. For the preclinical review, interventional studies of MSC therapyusing in vivo animal models of subacute or chronic stroke were included. Measures of safety and efficacy were assessed. Eleven clinical and 76 preclinical studies were included. Preclinically, MSC therapy was associated with significant benefits for multiple measures of motor and neurological function. Clinically, MSC therapy appeared to be safe, with no increase in adverse events reported (with the exception of self-limited fever immediately following injection). However, the efficacy of treatment was less apparent, with significant heterogeneity in both study design and effect size being observed. Additionally, in the only randomized phase II study to date, efficacy of MSC therapy was not observed. Preclinically, MSC therapy demonstrated considerable efficacy. Although MSC therapy demonstrated safety in the clinical setting, efficacy has yet to be determined. Future studies will need to address the discordance in the continuity of evidence as MSC therapy has been translated from "bench-to-bedside".