Early Phase Of Ischemic Stroke Research Articles

Association of Admission CRP Level with Short Term Outcome in Patients with Acute Ischemic Stroke

Acute ischemic stroke is very common in Bangladesh and one of the most common causes of physical disability and death. This study was performed to determine the prognostic value of CRP measured in the very early phase of ischemic stroke for short term functional outcome of patients with acute ischemic stroke. This observational study was carried out in the departments of Medicine and Neurology of Faridpur Medical College Hospital, Faridpur from July 2012 to December 2012. Total 100 patients of acute ischemic stroke were recruited in this study. Blood sample was collected for CRP level during the time of admission. In this study 26% of patients were in low CRP group (CRP <3 mg/L), 34% of patients were in medium CRP group (CRP 3-9.9 mg/L), 40% of patients were in high CRP group (CRP ≥10 mg/L). According to modified Rankin Scale (mRS) scoring system the high CRP group having a 44% risk for a poor outcome (mRS ≥3 ) vs 27% for the low CRP group ( p = 0.01). According to Barthel Index (BI) scoring system the high CRP group having a 45% risk for a poor outcome (BI <95) vs. 25% for the low CRP group (p = 0.002). Z test of proportion revealed significant association between high CRP level and poor short-term outcome of patients with acute ischemic stroke. Bangabandhu Sheikh Mujib Med. Coll. J. 2024;3(1):12-15

Salvianolic acid C attenuates cerebral ischemic injury through inhibiting neuroinflammation via the TLR4-TREM1-NF-κB pathway

BackgroundStroke is a leading cause of mortality and disability with ischemic stroke being the most common type of stroke. Salvianolic acid C (SalC), a polyphenolic compound found in Salviae Miltiorrhizae Radix et Rhizoma, has demonstrated therapeutic potential in the recovery phase of ischemic stroke. However, its pharmacological effects and underlying mechanisms during the early stages of ischemic stroke remain unclear. This study aimed to examine the potential mechanism of action of SalC during the early phase of ischemic stroke using network pharmacology strategies and RNA sequencing analysis.MethodsSalC effects on infarct volume, neurological deficits, and histopathological changes were assessed in a mouse model of transient middle cerebral artery occlusion (tMCAO). By integrating RNA sequencing data with a cerebral vascular disease (CVD)-related gene database, a cerebral ischemic disease (CID) network containing dysregulated genes from the tMCAO model was constructed. Network analysis algorithms were applied to evaluate the key nodes within the CID network. In vivo and in vitro validation of crucial targets within the identified pathways was conducted.ResultsSalC treatment significantly reduced infarct volume, improved neurological deficits, and reversed pathological changes in the tMCAO mouse model. The integration of RNA sequencing data revealed an 80% gene reversion rate induced by SalC within the CID network. Among the reverted genes, 53.1% exhibited reversion rates exceeding 50%, emphasizing the comprehensive rebalancing effect of SalC within the CID network. Neuroinflammatory-related pathways regulated by SalC, including the toll-like-receptor 4 (TLR4)- triggering receptor expressed on myeloid cells 1 (TREM1)-nuclear factor kappa B (NF-κB) pathway, were identified. Further in vivo and in vitro experiments confirmed that TLR4-TREM1-NF-κB pathway was down-regulated by SalC in microglia, which was essential for its anti-inflammatory effect on ischemic stroke.ConclusionsSalC attenuated cerebral ischemic injury by inhibiting neuroinflammation mediated by microglia, primarily through the TLR4-TREM1-NF-κB pathway. These findings provide valuable insights into the potential therapeutic benefits of SalC in ischemic stroke.

Advancing stroke therapy: A deep dive into early phase of ischemic stroke and recanalization.

Ischemic stroke, accounting for the majority of stroke events, significantly contributes to global morbidity and mortality. Vascular recanalization therapies, namely intravenous thrombolysis and mechanical thrombectomy, have emerged as critical interventions, yet their success hinges on timely application and patient-specific factors. This review focuses on the early phase pathophysiological mechanisms of ischemic stroke and the nuances of recanalization. It highlights the dual role of neutrophils in tissue damage and repair, and the critical involvement of the blood-brain barrier (BBB) in stroke outcomes. Special emphasis is placed on ischemia-reperfusion injury, characterized by oxidative stress, inflammation, and endothelial dysfunction, which paradoxically exacerbates cerebral damage post-revascularization. The review also explores the potential of targeting molecular pathways involved in BBB integrity and inflammation to enhance the efficacy of recanalization therapies. By synthesizing current research, this paper aims to provide insights into optimizing treatment protocols and developing adjuvant neuroprotective strategies, thereby advancing stroke therapy and improving patient outcomes.

Thrombo-inflammatory prognostic score can predict the outcome of stroke: a retrospective cohort study.

Inflammatory and thrombotic biomarkers are simple prognostic indicators of adverse clinical outcomes in patients with ischemic stroke (IS). However, isolated assessment of inflammatory or thrombus biomarkers in patients with IS is limited in clinical practice. This study aimed to evaluate the predictive value of a novel, simplified thrombo-inflammatory prognostic score (TIPS) that combines both inflammatory and thrombus biomarkers in the early phase of IS and to identify high-risk patients at the time of admission. The study population comprised 915 patients with a primary diagnosis of IS in the emergency departments of five grade A tertiary hospitals in China. Patients were divided into two groups based on the modified Rankin Scale (mRS): <3 and ≥3. TIPS with a value of "2" indicates biomarkers for high inflammation and thrombosis, "1" represents a biomarker, and "0" signals the absence of a biomarker. Multivariate logistic regression analysis was employed to identify the association between TIPS and clinical outcomes. TIPS was an independent predictor of unfavorable functional outcomes and mortality. It had a superior predictive value for clinical outcomes compared to the National Institutes of Health Stroke Scale (NIHSS) (effect ratio, 37.5%), D-dimer (effect ratio, 12.5%), and neutrophil-to-lymphocyte ratio (effect ratio, 25%). The survival probability of TIPS with a score of 0 is twice as high as that of TIPS with a score of 2. The survival rate for TIPS with a score of 1 is one time higher than that for TIPS with a score of 2. The predictive value of TIPS for unfavorable functional outcomes is represented by an AUC of 0.653. TIPS is associated with an increased risk of death and unfavorable functional outcomes in patients with IS and may be a useful tool for identifying high-risk patients at the time of admission.

Persistent High Pulse Pressure in Acute Non-Cardiogenic Ischemic Stroke as a Predictor of Neurological Deterioration and Recurrence of Ischemic Stroke: ADS Post-Hoc Analysis.

Studies investigating the relationship between pulse pressure (PP) and prognosis in acute ischemic stroke remain limited. Thus, in this study, we aim to determine whether changes in PP in the early phase of ischemic stroke are associated with neurological deterioration or stroke recurrence. Patients who participated in the Acute Aspirin Plus Cilostazol Dual Therapy for Non-cardiogenic Stroke Patients Within 48 Hours of Symptom Onset (ADS) trial were included in this study. We then divided the patients into four groups (low-low, low-high, high-low, high-high) according to low or high PP both on admission and 24 h after admission. The threshold PP calculated by receiver operating characteristic curve analysis of PP on admission for neurological deterioration within 14 days and recurrent ischemic stroke/transient ischemic attack (TIA) within 3 months was 69 mmHg. Neurological deterioration within 14 days was observed in 118 patients (10.6%), whereas recurrent ischemic stroke/TIA within 3 months was noted in 34 patients (3.2%). Among these four groups, both neurological deterioration within 14 days (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.12-3.91; p=0.0209) and recurrent ischemic stroke/TIA within 3 months (OR 4.80; 95% CI 1.62-14.86; p=0.0064) were significantly more frequent in the high-high group than in the low-low group as per the results of our multivariate analysis. In addition, neurological deterioration within 14 days was significantly higher in the high-low group than that in the low-low group (OR 2.70; 95% CI 1.44-5.05; p=0.0019). High PP during the acute phase of ischemic stroke appears to be associated with ischemic stroke recurrence and neurological deterioration, particularly if PP is elevated both on admission and 24 h later after admission.

Evaluation of a novel scoring system based on thrombosis and inflammation for predicting stroke-associated pneumonia: A retrospective cohort study.

Inflammation and thrombosis are involved in the development of stroke-associated pneumonia (SAP). Our aim was to evaluate the predictive value of a novel, simplified, thrombo-inflammatory prognostic score (TIPS) that combines both inflammatory and thrombus biomarkers in the early phase of ischemic stroke (IS). The study population consisted of 897 patients with a first diagnosis of IS admitted to the emergency department of five tertiary hospitals in China. Of these, the data from 70% of patients was randomly selected to derive the model and the other 30% for model validation. A TIPS of "2" was indicative of high inflammation and thrombosis biomarkers and "1" of one biomarker, with "0" indicative of absence of biomarkers. Multivariate logistic regression analyses were used to identify the association between TIPS and SAP. The TIPS was an independent predictor of SAP and 90-day mortality, with the incidence of SAP being significantly higher for patients with a high TIPS. The TIPS provided superior predictive value for SAP than clinical scores (A2DS2) and biomarkers currently used in practice, for both the derivation and validation sets. Mediation analysis revealed that TIPS provided a predictive value than either thrombotic (NLR) and inflammatory (D-dimer) biomarkers alone. The TIPS score may be a useful tool for early identification of patients at high-risk for SAP after IS.

Association of concomitant headache with hypoperfusion in ischemic stroke: A multimodal CT-based study.

Previous investigations indicate that vessel wall elasticity may contribute to the occurrence of an ischemic stroke-associated headache. In this prospective study, the association between radiologic parameters of intracranial hemodynamic changes and concomitant headaches during the early phase of ischemic stroke was examined. Consecutive patients with acute ischemic stroke (AIS) from the First Affiliated Hospital of Soochow University were recruited and divided into two groups according to their questionnaire results and the International Classification of Headache Disorder 3 criteria. Baseline data, including stroke sub-types and neurological function, at admission and discharge were collected. Non-contrast computed tomography (CT), CT angiography, and CT perfusion were performed to assess intracranial hemodynamic changes. Multiple adjusted logistic models were used and possible confounding factors were included in sequential models. A total of 190 patients with AIS (93 headaches and 97 non-headache) were recruited. There were significant differences between the two groups in gender, hypertension, Alberta stroke program early CT score, relative cerebral blood flow (rCBF), and relative cerebral blood volume (rCBV). Furthermore, rCBV (adjusted odds ratio [OR] 0.160; 95% confidence interval [CI], 0.055-0.461; p < 0.001) and rCBF (adjusted OR, 0.309; 95% CI, 0.113-0.844; p < 0.05) were significantly associated with concomitant headache during the early phase of AIS in fully adjusted models. After adjusting for sociodemographic characteristics and other confounding factors, p values for the ORs were robust and intensified. Patients with lower rCBV and rCBF tended to experience the concomitant headache during the early phase of AIS. Regional hypoperfusion and microcirculation might play an important role in this separate clinical entity.

Substance P Reduces Infarct Size and Mortality After Ischemic Stroke, Possibly Through the M2 Polarization of Microglia/Macrophages and Neuroprotection in the Ischemic Rat Brain.

Substance-P (SP) is an 11 amino acid neuropeptide that is known to stimulate the peripheral mobilization of bone marrow mesenchymal stem cells and M2 polarization in monocytes/macrophages in a variety of acute and chronic tissue injuries. To examine the role of SP in protection and recovery from acute ischemic brain injury, experimental ischemic stroke was induced by transient middle cerebral artery occlusion (tMCAo) in rats for 1h with subsequent reperfusion. Two injections of SP, immediately and one day post-tMCAo, resulted in approximately threefold lower mortality and 40% less infarct volume than those of saline-treated rats at seven days post-tMCAo. At 4.5h, SP markedly increased CD11b/c+CD163+/CD 206+ cells in the blood, which were concomitantly decreased in the bone marrow, suggesting that SP preferentially mobilized M2-polarized monocytes. After two days, SP increased the expression of neuroprotective and anti-inflammatory genes in the ischemic brain and induced neuronal survival in the brain penumbra. Additionally, SP markedly increased CD68+CD163+ and CD68+CD206+ M2 microglia/macrophages in the ischemic brain during seven days post-tMCAo. Furthermore, SP preserved the blood‒brain barrier in the ischemic brain, which was confirmed by the abundant levels of SMI71+ brain endothelial cells that colocalized with α-SMA+ pericytes. The beneficial effects of SP on functional recovery and tissue preservation were maintained for six weeks. Collectively, SP treatment in the early phase of ischemic stroke markedly suppressed the destructive inflammatory response and improved the microenvironment for tissue protection and repair.

3D transcranial ultrasound localization microscopy for discrimination between ischemic and hemorrhagic stroke in early phase

Early diagnosis is a critical part of the emergency care of cerebral hemorrhages and ischemia. A rapid and accurate diagnosis of strokes reduces the delays to appropriate treatments and a better functional recovery. Currently, CTscan and MRI are the gold standards with constraints of accessibility, availability, and possibly some contraindications. The development of Ultrasound Localization Microscopy (ULM) has enabled new perspectives to conventional transcranial ultrasound imaging with increased sensitivity, penetration depth, and resolution. The possibility of volumetric imaging has increased the field-of-view and provided a more precise description of the microvascularisation. In this study, rats (n = 9) were subjected to thromboembolic ischemic stroke or intracerebral hemorrhages prior to volumetric ULM at the early phases after onsets. Although the volumetric ULM performed in the early phase of ischemic stroke revealed a large hypoperfused area in the cortical area of the occluded artery, it showed a more diffused hypoperfusion in the hemorrhagic model. Respective computations of a Microvascular Diffusion Index highlighted different patterns of perfusion loss during the first 24 h of these two strokes’ subtypes. Our study provides the first proof that this methodology should allow early discrimination between ischemic and hemorrhagic stroke with a potential toward diagnosis and monitoring in clinic.

USP20 mitigates ischemic stroke in mice by suppressing neuroinflammation and neuron death via regulating PTEN signal

Ischemic stroke is a leading cause of death worldwide. The lack of effective pharmacotherapies for ischemic stroke is mainly attributed to the incomplete understanding of its pathogenesis. Deubiquitinase ubiquitin-specific protease 20 (USP20) plays an important role in regulating multiple cellular processes. However, its effects on cerebral ischemic stroke still remain unknown. In the present study, we found that USP20 expression was markedly increased in the early phase of ischemic stroke in mice with middle cerebral artery occlusion (MCAO) operation, and were then considerably decreased in mice with ischemia reperfusion (I/R) injury. Double immunofluorescence staining showed USP20 abundance in both microglial cells and neurons. We then found that promoting USP20 expression remarkably ameliorated MCAO-induced ischemic brain injury, along with significantly reduced infarct volume, neurological scores and brain water contents. In addition, cognitive impairments in MCAO-operated mice were considerably alleviated by USP20 over-expression. Furthermore, USP20 over-expression dramatically restrained microglial activation, inflammatory response and neuronal death in mice with ischemic stroke. Moreover, our results indicated that phosphatase and tensin homolog (PTEN) expression was highly decreased in the infarct areas of MCAO-treated mice, while being greatly rescued by USP20 over-expression. All these effects mediated by USP20 during cerebral I/R injury were confirmed in the cultured primary microglial cells and cortical neurons stimulated by oxygen-glucose deprivation and reoxygenation (OGD/R). Mechanistically, we found that USP20 directly interacted with PTEN. Notably, suppressing PTEN with its specific inhibitor dramatically abolished the function of USP20 to ameliorate neuroinflammation and neuron death induced by OGD/R. Collectively, our results illustrated that USP20 could effectively mitigate the severity of cerebral ischemic stroke and improve behavior deficits in MCAO-operated mice, and identified the USP20/PTEN axis as a promising therapeutic target for ischemic stroke treatment.

Abstract P777: Statistical Modeling of Proteomic Signaling During Stroke in Patients Undergoing Thrombectomy

Introduction: The previously published Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol (clinicaltrials.gov NCT03153683) utilizes mechanical thrombectomy to obtain tissue samples for banking. Peripheral blood proximal to the clot and intracranial blood distal from the clot were isolated. Proteomic and statistical analyses revealed normalized (intracranial-systemic) CCL19 expression was a predictor of infarct volume. Statistical modeling analyses were used determine the CCL19-associated proteomic signaling network occurring during ischemic stroke relating to infarct volume. Methods: Arterial intracranial and systemic blood samples underwent analysis for inflammatory proteins using Proximity Extension Assay (PEA) via Olink (Olink Proteomics, Boston, MA). Systemic expression was used as an internal control to normalize expression in the intracranial blood. Bivariate regression was used to examine the relationship between the intracranial normalized CCL19 expression and infarct volume. A backwards stepwise regression was then used to determine a model of predictability of infarct volume by CCL19 and associated inflammatory proteins. Results: 25 subjects (&gt;18 yrs) with a mean infarct volume of 8,172 ± 82,284 mm 3 and mean infarct time of 513 ± 246 minutes were included in this study. Their median age was 64 (24-91) and 10 (40%) were male. 16 subjects (64%) had hypertension, 15 (60%) had BMI &gt; 25, and 6 (24%) had a previous stroke. The stepwise regression model shows normalized expression of 16 proteins correlated with an increase in infarct volume (p&lt;0.005): CCL20, CXCL1, OSM, CD6, OSMR, TGF-alpha, TRANCE, CXCL10, LIF-R, CCL19, CDCP1, Flt3L, CCL23, CD244, TRAIL, NOTCH1. Conclusions: In our model, the expression of these proteins were consistently changed, though the directionality differed. LIF-R, NOTCH1, TRAIL, CD6, CCL23, TGF-alpha, and CCL20 were positively correlated, while the expressions of Flt3L, OSM, OSMR, TRANCE, CD244, CDCP1, CXCL1, CXCL10, and CCL19 were negatively correlated with infarct volume. This model depicts the proteomic signaling occurring during stroke in relationship to infarct volume, which reveals potential biomarkers and therapeutic targets for the early phase of ischemic stroke.

ACSL4 exacerbates ischemic stroke by promoting ferroptosis-induced brain injury and neuroinflammation

Acyl-CoA synthetase long-chain family member 4 (ACSL4) is an important isozyme for polyunsaturated fatty acids (PUFAs) metabolism that dictates ferroptosis sensitivity. The role of ACSL4 in the progression of ischemic stroke is unclear. Here, we found that ACSL4 expression was suppressed in the early phase of ischemic stroke and this suppression was induced by HIF-1α. Knockdown of ACSL4 protected mice against brain ischemia, whereas, forced overexpression of ACSL4 exacerbated ischemic brain injury. ACSL4 promoted neuronal death via enhancing lipid peroxidation, a marker of ferroptosis. Moreover, knockdown of ACSL4 inhibited proinflammatory cytokine production in microglia. These data identify ACSL4 as a novel regulator of neuronal death and neuroinflammation, and interventions of ACSL4 expression may provide a potential therapeutic target in ischemic stroke.

YTHDC1 mitigates ischemic stroke by promoting Akt phosphorylation through destabilizing PTEN mRNA

YTH Domain Containing 1 (YTHDC1) is one of the m6A readers that is essential for oocyte development and tumor progression. The role of YTHDC1 in neuronal survival and ischemic stroke is unknown. Here, we found that YTHDC1 was unregulated in the early phase of ischemic stroke. Knockdown of YTHDC1 exacerbated ischemic brain injury and overexpression of YTHDC1 protected rats against brain injury. Mechanistically, YTHDC1 promoted PTEN mRNA degradation to increase Akt phosphorylation, thus facilitating neuronal survival in particular after ischemia. These data identify YTHDC1 as a novel regulator of neuronal survival and modulating m6A reader YTHDC1 may provide a potential therapeutic target for ischemic stroke.

Interferon-β alleviates delayed tPA-induced adverse effects via modulation of MMP3/9 production in ischemic stroke

AbstractTissue plasminogen activator (tPA) is the only US Food and Drug Administration (FDA)–approved drug for ischemic stroke. However, delayed tPA administration is associated with increased risk of blood-brain barrier (BBB) disruption and hemorrhagic transformation (HT). Interferon-β (IFNβ), an FDA-approved drug for the treatment of multiple sclerosis, is a cytokine with immunomodulatory properties. Previous studies, including ours, demonstrated that IFNβ or type I IFN receptor signaling conferred protection against ischemic stroke in preclinical models, suggesting IFNβ might have translational therapeutic potential for the treatment of ischemic stroke. Currently, whether IFNβ could be coadministered with tPA to alleviate delayed tPA-induced adverse effects remains unknown. To elucidate that, IFNβ was coadministered with delayed tPA to ischemic stroke animals, and the severity and pathology of ischemic brain injury were assessed. We found delayed tPA treatment exacerbated ischemic brain injury, manifested by aggravated BBB disruption and HT. Notably, IFNβ ameliorated delayed tPA–exacerbated brain injury and alleviated adverse effects. Mechanistic studies revealed IFNβ suppressed tPA-enhanced neuroinflammation and MMP3/9 production in the ischemic brain. Furthermore, we identified IFNβ suppressed MMP9 production in microglia and attenuated tight junction protein degradation in brain endothelial cells. Moreover, we observed that peripheral immune cells may participate to a lesser extent in delayed tPA–exacerbated brain injury during the early phase of ischemic stroke. In conclusion, we provide the first evidence that IFNβ can be coadministered with tPA to mitigate delayed tPA–induced adverse effects of BBB disruption and HT that could potentially extend the tPA therapeutic window for the treatment of ischemic stroke.

Increased GABAergic inhibitory function against ischemic long-term potentiation in the CA1 region of the hippocampus

Potentiation of N-methyl-D-aspartate receptor (NMDAR)-mediated excitatory synaptic plasticity around 1 h after brief exposure to anoxia/aglycemia is called ischemic long-term potentiation (iLTP), which is considered a pathological form of synaptic response during the early phase of ischemic stroke. It is known that GABAergic inhibitory transmission is also an important molecular process involved in synaptic plasticity and learning memory. However, whether GABAergic transmission is involved in iLTP and early-phase plasticity in ischemic stroke remains unknown. In this study, iLTP was found to be induced in the hippocampal Schaffer-collateral pathway by exposure to oxygen glucose deprivation (OGD). Western blot analysis was conducted to analyze excitatory synaptic receptors and inhibitory synaptic receptors following OGD. The β3 subunit of the GABAA receptor (GABAAR) was markedly reduced, whereas the GluN2B subunit of the NMDAR was increased in the hippocampal area in the OGD group. Using extracellular recording, we demonstrated that application of GABAAR agonist midazolam could abolish the hippocampal iLTP. Moreover, midazolam had no significant effect on the increase in NMDAR subunit GluN2B, but ameliorated the reduction in the β3 subunit of GABAAR after OGD. In summary, our results indicated that hippocampal GABAAR reduction promoted synaptic potentiation after OGD. Activation of GABAergic inhibitory transmission function could inhibit iLTP; thus, modulation of GABAergic function is a protective treatment method in the acute phase of synaptic plasticity in ischemic stroke.

P3715Impact of sleep-disordered breathing on short-term functional outcomes in ischemic stroke patients: a cardiopulmonary coupling analysis using holter-monitoring

Abstract Background Sleep-disordered breathing (SDB) assessed by conventional polysomnography is reported to have close association with worsened clinical outcomes in patients with ischemic stroke. The cardiopulmonary coupling (CPC) analysis using Holter-monitoring is an easily assessable method to evaluate SDB. However, its prognostic impact needs to be investigated. Purpose The present study investigated the prognostic impact of SDB defined by CPC analysis using Holter-monitoring at early stage of ischemic stroke on the functional disability at 3-month follow-up. Methods Total 692 patients with acute ischemic stroke who underwent Holter-monitoring were enrolled. The CPC analysis was conducted and SDB was defined as the presence of narrow-band (NB) coupling during sleep time. We investigated the association between SDB and functional disability at 3-month measured by modified Rankin scale (mRS). Result The NB coupling was present in 216 (31.2%) of 692 patients with mean age of 64.2±12.8 years. The NB group showed significantly higher proportion of severe functional disability (mRS ≥3; 45.3% vs. 12.3%, p&lt;0.001) and persistent disability (ΔmRS≤0; 42.6% vs. 56.4%, p&lt;0.001) after 3-month. In multivariate analysis, the presence of NB coupling was an independent predictor of higher risk of both severe and persistent functional disability (HR: 3.97; 95% CI: 2.37–6.64; p&lt;0.001; and HR 1.92; 95% CI: 1.34–2.77; p&lt;0.001, respectively). The results were consistent after propensity-score matched analysis with 175 patient pairs (C-statistics=0.759). Parameters of functional disability Overall population (n=692) PSM population (n=350) no NB (n=476) NB (n=216) OR (95% CI) p-value no NB (n=175) NB (n=175) OR (95% CI) p-value Initial NIHSS ≥5 89 (18.6) 81 (37.5) &lt;0.001 52 (29.7) 52 (29.7) &gt;0.999 Discharge mRS ≥3 146 (30.6) 126 (58.3) &lt;0.001 90 (51.4) 89 (50.8) 0.915 3-month mRS ≥3 59 (12.3) 98 (45.3) 5.86 (4.00–8.60) &lt;0.001 38 (21.7) 72 (41.1) 2.52 (1.57–4.02) &lt;0.001 3-month ΔmRS ≤0 (persisent disability) 203 (42.6) 122 (56.4) 1.74 (1.26–2.41) 0.001 77 (44.0) 100 (57.1) 1.69 (1.11–2.58) 0.014 Data are expressed as n (%). mRS = modified Rankin's scale; NB = narrow-band; NIHSS = National Institutes of Health Stroke Scale; OR = odds ratio; PSM = propensity-score matched. Functional disabilities after 3-month Conclusion SDB assessed by CPC analysis at early phase of ischemic stroke was able to predict both greater and persistent functional disability at 3-month. The CPC analysis using Holter-monitoring is a useful modality for predicting functional disabilities in acute ischemic stroke.

P5744Sleep-disordered breathing assessed by holter-monitoring is associated to worsened one-year clinical outcomes in ischemic stroke patients: a cardiopulmonary coupling analysis

Abstract Background Sleep-disorder breathing (SDB) using polysomnography is closely associated to poor functional and clinical outcomes in ischemic stroke patients. The cardiopulmonary coupling analysis using Holter-monitoring (CPC-Holter analysis) is an emerging feasible modality to investigate SDB. Purpose We investigated the association between SDB defined by CPC-Holter analysis and one-year clinical outcome in patients with acute ischemic stroke. Methods Total 666 patients with acute ischemic stroke who underwent Holter-monitoring were enrolled. The CPC-Holter analysis was conducted and SDB was defined as the presence of narrow-band (NB) coupling during sleep time. Primary outcome was recurrent ischemic stroke, and secondary outcome was major adverse cerebrovascular event (MACE), a composite of recurrent ischemic stroke, transient ischemic attack, and all-cause mortality within one year since discharge. Result The NB coupling was present in 205 (30.8%) of 666 patients with mean age of 64.1±12.8 years. The NB group showed significantly higher incidence of both recurrent ischemic stroke (8.3% vs. 1.4%, p&lt;0.001) and MACE (14.9% vs. 3.0%, p&lt;0.001) within one-year. In multivariate analysis, presence of NB coupling remained as an independent predictor of both recurrent ischemic stroke and MACE (HR: 4.81; 95% CI: 1.73–13.4; p=0.003; and HR 4.17; 95% CI: 1.74–10.0; p&lt;0.001, respectively). The results were consistent after propensity-score matched analysis with 164 patient pairs (C-statistics=0.757). One-year clinical outcomes Overall population (n=666) PSM population (n=328) no NB (=461) NB (n=205) Log-rank p-value OR (95% CI) no NB (n=164) NB (n=164) Log-rank p-value OR (95% CI) Recurrent ischemic stroke 6 (1.4) 14 (8.3) &lt;0.001 5.73 (2.20–14.9) 3 (2.0) 11 (8.1) 0.026 3.85 (1.07–13.8) Transient ischemic attack 3 (0.7) 3 (1.7) 0.275 2 (1.3) 3 (2.1) 0.633 Hemorrhagic stroke 0 (0.0) 2 (1.2) 0.027 0 (0.0) 2 (1.5) 0.148 Total death 3 (0.7) 9 (4.8) 0.001 2 (1.3) 3 (1.9) 0.641 MACEs 12 (3.0) 25 (14.9) &lt;0.001 4.63 (2.06–10.4) 7 (5.2) 17 (13.1) 0.030 2.95 (1.06–8.21) Data are expressed as n (%). CI = confidence interval; MACE = major adverse cardiovascular event; NB = narrow-band; OR = odds ratio. One-year clinical outcomes Conclusion SDB assessed by CPC-Holter analysis at early phase of ischemic stroke is a powerful prognostic marker for predicting one-year adverse clinical outcomes. The CPC analysis using Holter-monitoring is a useful modality and could be easily applied to predict clinical outcomes in acute ischemic stroke patients.

Effects of Blood Pressure in the Early Phase of Ischemic Stroke and Stroke Subtype on Poststroke Cognitive Impairment.

Blood pressure (BP) control in the early phase of stroke is controversial to reduce the risk of poststroke cognitive impairment (PSCI). This study was to investigate the impact of BP levels in the early phase of ischemic stroke and stroke subtype on PSCI. Seven hundred and ninety-six patients with acute ischemic stroke were included. Cognitive function was assessed after stroke onset using the Montreal Cognitive Assessment. Patients were divided into quintiles according to systolic BP and diastolic BP levels in the early phase. Subtype analyses were according to Trial of ORG 10172 in Acute Stroke Treatment classification (infarct cause) and Oxfordshire Community Stroke Project classification (infarct location). After adjusting for multiple variables, the quintiles with the lowest systolic BP (Q1, 102-127 mm Hg) and with the highest systolic BP (Q5, 171-215 mm Hg) were associated with increased PSCI risk (odds ratio, 1.83; 95% confidence interval, 1.64-2.28; P=0.007 in Q1; odds ratio, 2.32; 95% confidence interval, 1.74-2.90; P<0.001 in Q5) at 3 months as compared with the middle quintile (Q3, 143-158 mm Hg). Similar association was found in diastolic BP quintiles. The analysis of cerebral infarction subtype demonstrated that both large artery atherosclerosis and total anterior circulation infarct were associated with increased risk of PSCI at 3 months after adjusting for multiple variables (large artery atherosclerosis: odds ratio, 1.42; 95% confidence interval, 1.06-1.90; P=0.031; total anterior circulation infarct: odds ratio, 1.68; 95% confidence interval, 1.32-2.15; P=0.001). Lower or higher BP in the early phase of ischemic stroke was correlated with increased PSCI risk at 3 months. Maintaining systolic/diastolic BP in the levels of 143 to 158/93 to 102 mm Hg might be beneficial to reduce the occurrence of PSCI. Moreover, large artery atherosclerosis subtype and total anterior circulation infarct subtype were correlated with increased PSCI risk at 3 months. URL: https://www.chictr.org. Unique identifier: ChiCTR-TRC-14004804.

Blood pressures immediately following ischemic strokes are associated with cerebral perfusion and neurologic function.

The optimal range of blood pressure levels in the early phase of ischemic stroke with hypertension is still controversial. Based on our stroke registry database, we explored the relationship between blood pressure levels and cerebral perfusion in the early phase of ischemic stroke with hypertension and neurofunctional recovery at 3months after stroke. Total 732 stroke patients with hypertension were finally analyzed. Patients were divided into quintiles according to systolic blood pressure (SBP) and diastolic blood pressure (DBP) to perform multivariable logistic regression to analyze their relation with neurofunctional recovery, respectively. The cerebral perfusion levels displayed a reverse "U" shape curve with the change of blood pressure levels. Sufficient estimated cerebral blood flow (ECBF) in the early phase of ischemic stroke was associated with good neurofunctional recovery at 3months after stroke. The best neurofunctional recovery was observed in the middle quintiles with SBP at 161 to 177mmHg and DBP at 103 to 114mmHg, respectively. So maintaining appropriate blood pressure levels in the early phase of ischemic stroke might be beneficial to cerebral perfusion and neurofunctional recovery.

Therapeutic window for YC‑1 following glutamate‑induced neuronal damage and transient focal cerebral ischemia.

3-(5′-Hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1), has been demonstrated to inhibit platelet aggregation, vascular contraction and hypoxia-inducible factor 1 activity in vitro and in vivo. The present study investigated the neuroprotective efficacy of YC-1 in cultured neurons exposed to glutamate-induced excitotoxicity and in an animal model of stroke. In a cortical neuronal culture model, YC-1 demonstrated neurotoxicity at a concentration >100 µM, and YC-1 (10–30 µM) achieved potent cytoprotection against glutamate-induced neuronal damage. Additionally, YC-1 (30 µM) effectively attenuated the increase in intracellular Ca2+ levels. Delayed treatment of YC-1 (30 µM) also protected against glutamate-induced neuronal damage and cell swelling in cultured neurons, though only at 4 h post-treatment. In addition, immediate treatment of YC-1 (30 µM) following the exposure of cortical neurons to glutamate (300 µM) produced a marked reduction in intracellular pH. Delayed treatment of YC-1 (25 mg/kg) protected against ischemic brain damage in vivo, though only when administered at 3 h post-insult. Thus, YC-1 exhibited neuroprotection against glutamate-induced neuronal damage and in mice subjected to transient focal cerebral ischemia. This neuroprotection may be mediated via its ability to limit the glutamate-induced excitotoxicity. However, the neuroprotective therapeutic window of YC-1 is only at 3 h in vivo and 4 h in vitro, which may, at least in part, be attributed to its ability to reduce the intracellular pH in the early phase of ischemic stroke. Although YC-1 provided the potential for clinical therapy, the treatment time point must be carefully evaluated following ischemia.