Acute Phase Of Stroke Research Articles

Inhibition of PCSK9 Protects against Cerebral Ischemia‒Reperfusion Injury via Attenuating Microcirculatory Dysfunction.

Proprotein convertase substilin/kexin type 9 (PCSK9), a pivotal protein regulating lipid metabolism, has been implicated in promoting microthrombotic formation and inflammatory cascades, thereby contributing to cardiovascular ischemia/reperfusion (I/R) injury. However, its involvement in cerebral I/R injury and its potential role in microcirculation protection remain unexplored. In this investigation, we utilized a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to simulate ischemic stroke. Different concentrations of evolocumab (1, 5, 10mg/kg, i.v.), a PCSK9 inhibitor, were administered to assess its impact. Immunofluorescence staining was employed to analyze changes in the expression of occludin, claudin-5, thrombocyte, ICAM-1, VCAM-1, and CD45, providing insights into blood-brain barrier integrity, platelet adhesion, and immune cell infiltration. Moreover, the Morris water maze and elevated plus maze were utilized to evaluate neurological and behavioral functions in MCAO/R mice, shedding light on the effects of PCSK9 inhibition. Our findings revealed a surge in plasma PCSK9 levels post-MCAO/R, peaking at 24h post-reperfusion. Evolocumab (10mg/kg) treatment significantly mitigated brain infarction and neurological deficits, evidenced by enhanced locomotor function and reduced post-stroke anxiety. However, it did not ameliorate cognitive impairment following MCAO/R. Additionally, evolocumab administration led to diminished leakage of evans blue solution and upregulated expression of occludin and claudin-5. Thrombocyte, ICAM-1, VCAM-1, and CD45 levels were notably reduced in the penumbral area post-evolocumab treatment. These protective effects are speculated to be mediated through the inhibition of the ERK/NF-κB pathway. The PCSK9 inhibitor evolocumab holds promise as a therapeutic agent during the acute phase of stroke, exerting its beneficial effects by modulating the ERK/NF-κB signaling pathway.

Functional Outcome Prediction of Acute Ischemic Stroke Based on the Oral and Gut Microbiota.

Although several studies have identified a distinct gut microbiota in individuals with acute ischemic stroke (AIS), there is a limited amount of research that has simultaneously investigated alterations in the oral and intestinal microbiota in AIS patients and their correlation with clinical prognosis. This was a prospective and observational single-center cohort study in which we included 160 AIS patients who were admitted within 24h after a stroke event. We collected oral and rectal swab samples for analysis using 16S rRNA high-throughput sequencing. Our study revealed that patients with unfavorable outcomes after AIS showed early disruptions in their oral and intestinal microbiota. Rectal swabs showed increased levels of facultatively anaerobic bacteria in patients with a poor prognosis, while the oral cavity exhibited higher levels of anaerobic and opportunistic pathogenic bacteria. By employing machine learning analysis, we found that the microbiota composition at both rectal and oral sites could predict early and long-term outcomes. Moreover, patients with a poor prognosis displayed increased oral bacterial colonization in the rectal microbiota and altered interactions between the oral and gut microbiota. This study reveals distinct rectal and oral bacteria that could predict unfavorable outcomes for AIS patients. Monitoring the microbiota of various body sites during the early stages after admission may hold prognostic value and inform personalized treatment strategies. The presence of oral bacteria colonizing the intestines during the acute phase of stroke could serve as an early indication of poor outcomes for AIS patients.

Rodent ischemic stroke models and their relevance in preclinical research

AbstractStroke is a leading cause of death and disability worldwide, with ischemic stroke caused by an occluded vessel accounting for the majority of cases. Current treatments are limited to recanalization, either through thrombectomy or thrombolysis. Approved pharmacological interventions to suppress stroke‐associated excitotoxicity and neuroinflammatory events, leading to brain tissue death, are still lacking. Although numerous preclinical studies have been performed, they have yet to be translated into clinically relevant interventions. First‐line preclinical in vivo studies include the use of rodent ischemic stroke models, which vary in terms of how well they replicate human stroke pathophysiology and phenotype (including the formation of blood clot, blood–brain barrier disruption, neuroinflammation, and edema generation). Thus, rodent ischemic stroke models must be carefully chosen according to the specific pharmacological intervention to be tested. In this review, we aimed to provide an overview of the five most commonly used rodent ischemic stroke models and critically assess their advantages and limitations, with a primary focus on the acute phases of stroke.

A parallel-group randomized controlled trial of blue light versus red light for improving sleep, fatigue, and cognition following stroke: Pilot results and recommendations for further study

BackgroundDisordered sleep and fatigue are common in the acute phase of stroke and can impede recovery. ObjectiveA randomized parallel group placebo-controlled pilot study compared daily morning exposure to blue light or red light (placebo) for improving daytime sleepiness, fatigue, nocturnal sleep, and cognition in patients receiving inpatient rehabilitation for acute stroke. Methods43 patients with disordered sleep secondary to first episode stroke (n = 34 ischemic, n = 9 hemorrhagic; aged 66.2 ± 14.1 years) were randomized to receive 25 min of blue or red light for 5 or more days depending on inpatient rehabilitation length of stay (blue-light n = 21, red-light n = 22). At baseline and study discharge, daytime sleepiness was measured with the Karolinska Sleepiness Scale and Wits Pictorial Sleepiness Scale, fatigue with a visual analogue scale, and cognitive function with the Rey Auditory Verbal Learning Test and Trail Making Test (TMT). Wrist actigraphs measured nocturnal sleep parameters. Effect sizes were used to estimate sample sizes for larger studies. ResultsBlue light exposure led to significant improvements in daytime sleepiness, fatigue, auditory verbal learning, and time to sleep onset (all p < .05) relative to red light exposure (effect size range 0.75 to 1.83). Change in TMT, minutes of nocturnal sleep, and number of awakenings after sleep onset were not statistically significant (effect sizes range 0.38 to 0.57). ConclusionMorning blue light exposure for 5 or more days after acute stroke led to greater improvements than red light exposure. Effect sizes suggest a larger study is warranted to confirm generalizability of pilot findings.Trial Registration:ClinicalTrials.govNCT03125967 (Registered 01/01/2017).

Near Complete Reversal Of Large Diffusion-Weighted Imaging Lesion After Thrombectomy: A Case Report And Literature Review.

Diffusion-Weighted Imaging (DWI) plays a crucial role in acute ischemic stroke (AIS), as it is used to evaluate the ischemic lesions that are irreversibly damaged. The reversibility of DWI ischemic lesions has been noted in patients with AIS who undergo revascularization therapy. In addition, the occurrence of this phenomenon in large ischemic regions remains rare, particularly the near-complete reversal of large DWI lesion cases. A 58-year-old male presented with a generalized tonic-clonic seizure. Emergent magnetic resonance imaging (MRI) revealed an extremely large infarction lesion in the right hemisphere with an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) value of 2 and occlusion of the terminal right internal carotid artery. The patient was immediately transferred to the Digital Subtraction Angiography (DSA) Unit for endovascular treatment with a stent retriever. After a rapid successful reperfusion with expanded treatment in cerebral infarction (eTICI) score of 3, the patient promptly recovered 24 hours after the procedure. A brain MRI was repeated after 8 days of admission, and interestingly, the DWI lesion showed significant reversal. The modified Rankin scale (mRS) at discharge was 2 and 1 at 90-day follow-up, respectively. Our case shows that the reversibility of DWI ischemic lesions can occur during the acute stroke phase, even in patients with extremely large regions, if rapid and successful reperfusion is achieved. The clinical implications of this phenomenon indicate that using DWI to evaluate the infarct core should be interpreted with caution.

Baseline Blood Pressure Was Associated with Hemispheric Cerebral Blood Flow in Acute Small Subcortical Infarcts

Introduction: While increased baseline blood pressure (BP) is a prevalent comorbidity in the acute phase of ischemic stroke, the association between baseline BP and the state of hemispheric perfusion in patients with acute small subcortical infarcts (SSIs) has not been studied in detail. The aim of this study was to investigate the relationship between baseline BP and hemispheric cerebral blood flow (CBF) in acute SSIs. Methods: This retrospective study included 101 patients with acute SSIs. Baseline hemispheric CBF was assessed through co-registration of baseline CT perfusion imaging and follow-up diffusion-weighted imaging. The association between baseline BP, CBF, and different cerebral small vessel disease (CSVD) biomarkers was assessed. Results: Baseline systolic BP (SBP) and diastolic BP (DBP) were negatively associated with contralateral hemispheric CBF after multivariate-adjusted linear analysis (SBP: β = −0.001, 95% CI: −0.002 to 0.000, p = 0.030; DBP: β = −0.002, 95% CI: −0.003∼0.001, p = 0.006). Among other CSVD biomarkers, the presence of any cerebral microbleeds showed a significant association with lower CBF in the contralateral hemisphere of the infarct lesion (r = −0.270, p = 0.035). Conclusion: In patients with acute SSIs, increased baseline BP was associated with reduced CBF in the contralateral hemisphere of the infarct lesion, which probably could be interpreted by the exacerbation of the CSVD burden, suggesting a potential mechanistic link between BP autoregulation dysfunction and the aggravation of neurovascular impairment in SSIs.

Prediction of Ischemic Stroke Functional Outcomes from Acute-Phase Noncontrast CT and Clinical Information.

Background Clinical outcome prediction based on acute-phase ischemic stroke data is valuable for planning health care resources, designing clinical trials, and setting patient expectations. Existing methods require individualized features and often involve manually engineered, time-consuming postprocessing activities. Purpose To predict the 90-day modified Rankin Scale (mRS) score with a deep learning (DL) model fusing noncontrast-enhanced CT (NCCT) and clinical information from the acute phase of stroke. Materials and Methods This retrospective study included data from six patient datasets from four multicenter trials and two registries. The DL-based imaging and clinical model was trained by using NCCT data obtained 1-7 days after baseline imaging and clinical data (age; sex; baseline and 24-hour National Institutes of Health Stroke Scale scores; and history of hypertension, diabetes, and atrial fibrillation). This model was compared with models based on either NCCT or clinical information alone. Model-specific mRS score prediction accuracy, mRS score accuracy within 1 point of the actual mRS score, mean absolute error (MAE), and performance in identifying unfavorable outcomes (mRS score, >2) were evaluated. Results A total of 1335 patients (median age, 71 years; IQR, 60-80 years; 674 female patients) were included for model development and testing through sixfold cross validation, with distributions of 979, 133, and 223 patients across training, validation, and test sets in each of the six cross-validation folds, respectively. The fused model achieved an MAE of 0.94 (95% CI: 0.89, 0.98) for predicting the specific mRS score, outperforming the imaging-only (MAE, 1.10; 95% CI: 1.05, 1.16; P < .001) and the clinical information-only (MAE, 1.00; 95% CI: 0.94, 1.05; P = .04) models. The fused model achieved an area under the receiver operating characteristic curve (AUC) of 0.91 (95% CI: 0.89, 0.92) for predicting unfavorable outcomes, outperforming the clinical information-only model (AUC, 0.88; 95% CI: 0.87, 0.90; P < .001) and the imaging-only model (AUC, 0.85; 95% CI: 0.84, 0.87; P < .001). Conclusion A fused DL-based NCCT and clinical model outperformed an imaging-only model and a clinical-information-only model in predicting 90-day mRS scores. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Lee in this issue.

Investigating the effects of excitatory and inhibitory somatosensory rTMS on somatosensory functioning in the acute and subacute phases of stroke: a preliminary double-blind and randomized trial.

Repetitive transcranial magnetic stimulation (rTMS) targeting the primary somatosensory cortex (S1) has a potential effect on somatosensory functioning following a stroke. However, S1-rTMS was combined with peripheral therapies in previous trials. Moreover, these studies have commonly targeted the ipsilesional S1 with excitatory rTMS paradigms. This double-blind, randomized trial (registration number: ChiCTR2200059098) investigated two forms of paradigms, that is ipsilesional excitatory and contralesional inhibitory rTMS, as a stand-alone treatment in post-stroke somatosensation. Patients in the acute and subacute phases of stroke were randomly assigned to either contralesional 1-Hz or ipsilesional 10-Hz rTMS group and received 10 daily sessions of treatment in two consecutive weeks. Results indicate that the contralesional inhibitory and ipsilesional excitatory stimulation were equally effective in improving somatosensory functioning. Moreover, this effect was most prominent in deep sensations and subjective sensations. Using single-pulse EMG recordings, our data also revealed an increased MEP amplitude in the ipsilesional motor cortex following ipsilesional excitatory treatment. This preliminary study demonstrates the primary somatosensory cortex as an effective rTMS target in somatosensory recovery following stroke. https://www.chictr.org.cn/showproj.html?proj=166474, ChiCTR2200059098.

Effects of motor imagery-based brain-computer interface-controlled electrical stimulation on lower limb function in hemiplegic patients in the acute phase of stroke: a randomized controlled study.

Lower limb motor dysfunction is one of the most serious consequences of stroke; however, there is insufficient evidence for optimal rehabilitation strategies. Improving lower limb motor function through effective rehabilitation strategies is a top priority for stroke patients. Neuroplasticity is a key factor in the recovery of motor function. The extent to which neuroplasticity-based rehabilitation therapy using brain-computer interface (BCI) is effective in treating lower limb motor dysfunction in acute ischemic stroke patients has not been extensively investigated. This study aimed to assess the impact of BCI rehabilitation on lower limb motor dysfunction in individuals with acute ischemic stroke by evaluating motor function, walking ability, and daily living activities. This study was conducted in a randomized controlled trial, involving 64 patients with acute ischemic stroke who experienced lower limb motor dysfunction. All patients were divided into two groups, with 32 patients assigned to the control group was given conventional rehabilitation once a day for 70 min, 5 times a week for 2 weeks, and the experimental group (n = 32) was given BCI rehabilitation on top of the conventional rehabilitation for 1 h a day, 30 min of therapy in the morning and an additional 30 min in the afternoon, for a total of 20 sessions over a two-week period. The primary outcome was lower extremity motor function, which was assessed using the lower extremity portion of the Fugl-Meyer Rating Scale (FMA-LE), and the secondary endpoints were the Functional Ambulation Scale (FAC), and the Modified Barthel index (MBI). After 20 sessions of treatment, both groups improved in motor function, walking function, and activities of daily living, and the improvements in FMA-LE scores (p < 0.001), FAC (p = 0.031), and MBI (p < 0.001) were more pronounced in the experimental group compared with the control group. Conventional rehabilitation therapy combined with BCI rehabilitation therapy can improve the lower limb motor function of hemiplegic patients with stroke, enhance the patient's ability to perform activities of daily living, and promote the improvement of walking function, this is an effective rehabilitation policy to promote recovery from lower extremity motor function disorders.

The Alteration of Circulating Invariant Natural Killer T, γδT, and Natural Killer Cells after Ischemic Stroke in Relation to Clinical Outcomes: A Prospective Case-Control Study.

The adaptive response occurs only after 7-10 days of antigen presentation. Nevertheless, the autoreactive T cells infiltrate the stroke lesion within the first 48 h. Thus, we hypothesized that the unconventional lymphocytes as invariant natural killer T cells (iNKT) and γδT cells that share immediate innate and delayed adaptive response features are involved in acute stroke pathophysiology. We assessed prospectively the quantity of circulating iNKT cells, γδT cells, and NK cells with flow cytometry in 52 subjects within three months after stroke, and we compared the results with those obtained in age-, sex-, and vascular risk factor-matched controls. We studied lymphocyte parameters regarding clinical outcomes, infarct volume, stroke-associated infection (SAI), and burden risk factors. The reduced number of circulating γδT cells and decreased percentage of the Vδ2 subset in the acute phase of stroke correlated with worse neurological status in the recovery phase. In subjects treated with thrombolysis and those who developed SAI, a lower percentage of γδT cells in the 90-day follow-up was observed. An increased percentage of iNKT cells in the acute and subacute phases of stroke was observed, and it was related to the worse clinical status. The circulating NK cells do not change temporarily or affect the outcomes after stroke. It seems that γδT cells play a long-lasting role in ischemic stroke, mainly related to the Vδ2 subset. The role of iNKT cells appears to be detrimental, especially in the acute and subacute phases of stroke. The effect of circulating NK cells on the outcome after stroke seems negligible.

Translatome analysis in acute ischemic stroke: Astrocytes and microglia exhibit differences in poststroke alternative splicing of expressed transcripts.

Astrocytes and microglia undergo dynamic and complex morphological and functional changes following ischemic stroke, which are instrumental in both inflammatory responses and neural repair. While gene expression alterations poststroke have been extensively studied, investigations into posttranscriptional regulatory mechanisms, specifically alternative splicing (AS), remain limited. Utilizing previously reported Ribo-Tag-seq data, this study analyzed AS alterations in poststroke astrocytes and microglia from young adult male and female mice. Our findings reveal that in astrocytes, compared to the sham group, 109 differential alternative splicing (DAS) events were observed at 4 h poststroke, which increased to 320 at day 3. In microglia, these numbers were 316 and 266, respectively. Interestingly, the disparity between DAS genes and differentially expressed genes is substantial, with fewer than 10 genes shared at both poststroke time points in astrocytes and microglia. Gene ontology enrichment analysis revealed the involvement of these DAS genes in diverse functions, encompassing immune response (Adam8, Ccr1), metabolism (Acsl6, Pcyt2, Myo5a), and developmental cell growth (App), among others. Selective DAS events were further validated by semiquantitative RT-PCR. Overall, this study comprehensively describes the AS alterations in astrocytes and microglia during the hyperacute and acute phases of ischemic stroke and underscores the significance of certain hub DAS events in neuroinflammatory processes.

Validity of evaluation scales for post-stroke depression: a systematic review and meta-analysis

BackgroundPost-stroke depression (PSD) is closely associated with poor stroke prognosis. However, there are some challenges in identifying and assessing PSD. This study aimed to identify scales for PSD diagnosis, assessment, and follow-up that are straightforward, accurate, efficient, and reproducible.MethodsA systematic literature search was conducted in 7 electronic databases from January 1985 to December 2023.ResultsThirty-two studies were included, the Patient Health Questionnaire-9 (PHQ-9) and Hamilton Depression Scale (HDRS) had higher diagnostic accuracy for PSD. The sensitivity, specificity, and diagnostic odds ratio of PHQ-9 or diagnosing any depression were 0.82, 0.87, and 29 respectively. And for HDRS, used for diagnosing major depression, the scores were 0.92, 0.89, and 94. Furthermore, these two scales also had higher diagnostic accuracy in assessing depressive symptoms during both the acute and chronic phases of stroke. In patients with post-stroke aphasia and cognitive impairment, highly diagnostic scales have not been identified for assessing depressive symptoms yet.ConclusionsThe PHQ-9 and HDRS scales are recommended to assess PSD. HDRS, which demonstrates high diagnostic performance, can replace structured interviews based on diagnostic criteria.

Optimizing serum electrolyte levels in stroke patients: a multimodal approach with soymilk supplementation.

Electrolyte imbalances are common in stroke patients and can significantly impact their overall health, potentially leading to severe complications and even fatal outcomes. In this study, we investigated the impact of combining multiple exercise training modalities (METM) with soymilk supplementation on serum electrolyte levels in stroke patients. In a single-blind, four-arm randomized clinical trial, 120 stroke patients were randomly assigned to one of the following groups: (1) the METM group, (2) the soymilk group, (3) the METM plus soymilk group, and (4) the control group. Changes in serum electrolyte levels were compared both within and across groups over four consecutive weeks. Upon admission, 38.3% of the participants presented with hyponatremia, 26.7% hypokalemia, and 73.3% hypocalcemia. Over time, there was an overall improvement in serum electrolyte imbalances across all study groups compared to the baseline. Between-group comparisons revealed that the METM plus soymilk group exhibited statistically significant improvements compared to the other groups with absolute reductions in the proportion of participants with hyponatremia, hypokalemia, and hypocalcemia by 43.3%, 33.3%, and 73.4%, respectively. The study findings substantiate the common occurrence of hyponatremia, hypokalemia, and hypocalcemia during the acute phase of stroke. Implementation of the METM alongside soymilk intake demonstrated potential in rectifying electrolyte imbalances among stroke patients, hinting at a promising intervention strategy.

Transcranial ultrasound with electrical stimulation of the cerebello-parietal nucleus on cerebral blood flow and limb function in patients with stroke.

To investigate the efficacy of transcranial ultrasound stimulation (TUS) combined with Fastigial nucleus stimulation (FNS) on cerebral blood flow and limb function in patients in the acute phase of ischemic stroke. A total of 90 patients in the acute phase of ischemic stroke were randomly divided into an FNS, TUS, and TUS + FNS group (30 patients each), and all patients also received conventional treatment. The FNS group was treated with FNS alone. The TUS group was treated with TUS alone. The TUS + FNS group was treated with both TUS and FNS. The three groups were treated once a day for 6 days a week. The simplified Fugl-Meyer Assessment (FMA) and Barthel index scores (BI), and the peak systolic blood flow velocity (Vs) and the mean blood flow velocity (Vm) of the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery, were significantly higher in all three groups compared with before treatment (P < 0.05). The scores for the TUS group were higher than for the FNS group (P < 0.05), and the scores of the TUS + FNS group were higher than the TUS and FNS groups, respectively (P < 0.05). The total effective rate was 63.3%, 70.0%, and 90.0% in the FNS, TUS, and TUS + FNS groups, respectively, and the difference between the three groups was statistically significant (P < 0.05). The FNS and TUS treatments improved the function of and accelerated cerebral blood flow in patients with acute ischemic stroke to different degrees, and the combined use of both treatment types was overall more effective.

Cortical compensation mechanism for swallowing recovery in patients with medullary infarction-induced dysphagia.

This study aims to examine brain activity during different swallowing actions in patients with dysphagia caused by medullary infarction (MI) before and after treatment using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. Fifteen patients were enrolled in this study. Brain activation during saliva swallowing and effortful saliva swallowing was observed using BOLD imaging in the acute phase of stroke and after 4 weeks of rehabilitation training. Differences in the activation of brain regions during saliva swallowing before and after treatment, during effortful saliva swallowing before and after treatment, and between the two swallowing actions before and after treatment were compared. In the acute phase of stroke, only the bilateral precentral and left lingual gyrus were partially activated during saliva swallowing, and there was no obvious activation in the insula. Effortful saliva swallowing activated more brain regions than saliva swallowing before treatment, including the bilateral supplementary motor area (SMA), postcentral gyrus, and right insular cortex. The number of brain regions activated during saliva swallowing increased after treatment, including the bilateral precentral gyrus, postcentral gyrus, insula, thalamus, and SMA. Cortical activation increases after recovery from dysphagia, and the increased activation of the postcentral gyrus might play a functional compensatory role. Effortful saliva swallowing is a more effective rehabilitation training method for patients with dysphagia caused by MI.

Morphological characteristics of the cerebral cortex of a mini-pig under conditions of gene therapy after experimental stroke

Aim. To study the effectiveness of preventive gene therapy (within 2 days) and gene therapy in the acute phase (after 4 hours) of ischemic stroke in mini-pigs using an autologous leucoconcentrate (AutoLeuc) enriched with recombinant genes of vascular endothelial growth factor (VEGF165), glial cell line-derived neurotrophic factor (GDNF) and neural cell adhesion molecule 1 (NCAM1), as well as the migration of leukocytes transduced with a chimeric adenoviral vector serotype 5 with fiber 35 serotype (Ad5/F35) and the green fluorescent protein (GFP) genome into immune defense organs.Materials and methods. The experiment was conducted on 8-month-old Vietnamese lop-bellied mini-pigs (n=16). An ischemic stroke was created by occlusion of the distal branches of the left middle cerebral artery and the right common carotid artery. Genetically modified AutoLeuc was administered preventively intravenously 2 days before or in the acute phase 4 hours after stroke modelling; the control group was injected with 30 ml of saline solution. The morphology of the cerebral cortex was assessed using histological methods in the areas bordering the infarction and peri-infarction after 21 days. The migration of genetically modified Ad5/F35-GFP leukocytes into the brain, spleen, and submandibular lymph nodes was studied a week after stroke modelling.Results. In the peri-infarction zone, the content of pyknotic neurons in control animals was higher, while the number of capillaries was lower than in the gene therapy groups. In the latter, neurons had a typical morphology with preserved outgrowths; in the control group, the outgrowths were tortuous and fragmented. Fluorescence microscopy after injection of AutoLeuc with Ad5/F35-GFP revealed GFP-positive cells in the spleen and submandibular lymph nodes.Conclusion. 21 days after modeling a stroke in mini-pigs against the background of preventive gene therapy or gene therapy in the acute phase using VEGF165/GDNF/NCAM1 AutoLeuc, greater preservation of neurons and a higher density of capillaries in the peri-infarction zone of ischemic brain damage were established. Leukocytes with Ad5/ F35-GFP were found in the spleen and submandibular lymph nodes.

Stroke Evaluation in the Interventional Suite Using Dual-Layer Detector Cone-Beam CT: aFirst-in-human Prospective Cohort Study (the Next GenerationX-ray Imaging System Trial).

Cone-beam CT in the interventional suite could be an alternative to CT to shorten door-to-thrombectomy time. However, image quality in cone-beam CT is limited by artifacts and poor differentiation between gray and white matter. This study compared non-contrast brain dual-layer cone-beam CT in the interventional suite to reference standard CT in stroke patients. Aprospective single-center study enrolled consecutive participants with ischemic or hemorrhagic stroke. The hemorrhage detection accuracy, per-region ASPECTS accuracy and subjective image quality (Likert scales for gray-white matter differentiation, structure perception and artifacts) were assessed by three neuroradiologists blinded to clinical data on dual-layer cone-beam CT 75 keV monoenergetic images compared to CT. Objective image quality was assessed by region-of-interest metrics. Non-inferiority for hemorrhage detection and ASPECTS accuracy was determined by the exact binomial test with aone-sided lower performance boundary prospectively set to 80% (98.75% CI). 27participants were included (74years ± 9; 19female) in the hyperacute or acute stroke phase. One reader missed asmall bleeding, but all hemorrhages were detected in the majority analysis (100% accuracy, CI lower boundary 86%, p = 0.002). ASPECTS majority analysis showed 90% accuracy (CI lower boundary 85%, p < 0.001). Sensitivity was 66% (individual readers 67%, 69%, and 76%), specificity was 97% (97%, 96%, 89%). Subjective and objective image quality were inferior to CT. In asmall single-center cohort, dual-layer cone-beam CT showed non-inferior hemorrhage detection and ASPECTS accuracy to CT. Despite inferior image quality, the technique may be useful for stroke evaluation in the interventional suite. NCT04571099 (clinicaltrials.gov). Prospectively registered 2020-09-04.

Flow augmentation therapies preserve brain network integrity and hemodynamics in a canine permanent occlusion model

The acute phase of ischemic stroke presents a critical window for therapeutic intervention, where novel approaches such as hyper-acute cerebral flow augmentation offer promising avenues for neuroprotection. In this study, we investigated the effects of two such therapies, NEH (a combination of norepinephrine and hydralazine) and Sanguinate (pegylated bovine carboxyhemoglobin), on resting-state functional connectivity, global mean signal (GMS), and blood oxygen level-dependent (BOLD) time lag in a pre-clinical canine model of stroke via permanent occlusion of the middle cerebral artery (total of n = 40 IACUC-approved mongrel canines randomly split into control/natural history and two treatment groups). Utilizing group independent component analysis (ICA), we identified and examined the integrity of sensorimotor and visual networks both pre- and post-occlusion, across treatment and control groups. Our results demonstrated that while the control group exhibited significant disruptions in these networks following stroke, the treatment groups showed remarkable preservation of network integrity. Voxel-wise functional connectivity analysis revealed less pronounced alterations in the treatment groups, suggesting maintained neural connections. Notably, the treatments stabilized GMS, with only minimal reductions observed post-occlusion compared to significant decreases in the control group. Furthermore, BOLD time-lag unity plots indicated that NEH and Sanguinate maintained consistent hemodynamic response timing, as evidenced by tighter clustering around the line of unity, suggesting a potential neuroprotective effect. These findings were underscored by robust statistical analyses, including paired T-tests and Mann–Whitney U tests, which confirmed the significance of the connectivity changes observed. The correlation of BOLD time-lag variations with neuroimaging functional biomarkers highlighted the impact of stroke and the efficacy of early therapeutic interventions. Our study supports the further study of flow augmentation therapies such as NEH and Sanguinate in stroke treatment protocols and suggests flow augmentation therapies should be further explored in an effort to improve patient outcomes.

Evaluating Serum Copeptin as a Promising Biomarker for Predicting Acute Ischaemic Stroke Severity: A Hospital-Based Study on Strokes.

Stroke is the second cause of mortality and the foremost leading cause of disability globally. Many potential biomarkers have been described to contribute to prognosticating the severity in the acute phase of stroke as well as help with risk stratification. Copeptin, an inactive peptide that is produced in an equimolar ratio to arginine vasopressin and adequately mirrors an individual's stress response to acute illnesses like acute ischaemic stroke as evidenced by elevated or increasing levels is being explored in this study to determine its relationship with acute stroke severity and infarct size on admission. This is a cross-sectional study of 80 neuroimaging-confirmed acute ischaemic patients who presented within seven days of symptom onset and 80 control subjects. The ischaemic stroke cases had stroke severity and infarct volume determined on admission by the National Institute of Health Stroke Scale (NIHSS) and neuroimaging (brain CT/MRI). A baseline serum copeptin level was measured in the study subjects. Spearman correlation and Kruskal Wallis test were used to determine the relationship between serum copeptin level with admission NIHSS and infarct size respectively. The receiver operating characteristic (ROC) curve was calculated to determine the sensitivity and specificity of copeptin to predict severity and outcome. The mean age of the study group was 61.3 ± 12.7 years with 55.0% males and 45.0% females. The serum level of copeptin was significantly higher in the stroke cases with a median of 28.6 pmol/L (interquartile range (IQR)- 15.4-31.6 pmol/L) versus 8.8 pmol/L (IQR- 3.2- 10.7 pmol/L) among the stroke-free controls (p= 0.001) at a statistically significant level. There was a weak correlation between copeptin and NIHSS calculated at admission to measure stroke severity (r- 0.02, p= 0.873). Patients with infarct sizes in the fourth quartile (infarct sizes greater than 18.78 cm3) had higher copeptin levels, though this was not statistically significant (H= 2.88; p= 0.410). Admission serum copeptin did not show a statistically significant prognostic value in predicting stroke severity and mortality in stroke patients who presented within seven days of symptomonset with an area under curve (AUC) of 0.51 (95% CI: 0.36-0.65; p= 0.982). In this study, copeptin was higher among the stroke cases compared with the stroke-free controls which suggests a significant prognostic value in risk stratification in the acute phase of stroke; however, this did not significantly correlate with stroke severity and thus warrants further study in this field to elucidate it's fascinating potential as a prognostic biomarker (especially in the acute period) as this may enable allocation of a better-focused therapy for stroke patients.

MSE-VGG: A Novel Deep Learning Approach Based on EEG for Rapid Ischemic Stroke Detection.

Ischemic stroke is a type of brain dysfunction caused by pathological changes in the blood vessels of the brain which leads to brain tissue ischemia and hypoxia and ultimately results in cell necrosis. Without timely and effective treatment in the early time window, ischemic stroke can lead to long-term disability and even death. Therefore, rapid detection is crucial in patients with ischemic stroke. In this study, we developed a deep learning model based on fusion features extracted from electroencephalography (EEG) signals for the fast detection of ischemic stroke. Specifically, we recruited 20 ischemic stroke patients who underwent EEG examination during the acute phase of stroke and collected EEG signals from 19 adults with no history of stroke as a control group. Afterwards, we constructed correlation-weighted Phase Lag Index (cwPLI), a novel feature, to explore the synchronization information and functional connectivity between EEG channels. Moreover, the spatio-temporal information from functional connectivity and the nonlinear information from complexity were fused by combining the cwPLI matrix and Sample Entropy (SaEn) together to further improve the discriminative ability of the model. Finally, the novel MSE-VGG network was employed as a classifier to distinguish ischemic stroke from non-ischemic stroke data. Five-fold cross-validation experiments demonstrated that the proposed model possesses excellent performance, with accuracy, sensitivity, and specificity reaching 90.17%, 89.86%, and 90.44%, respectively. Experiments on time consumption verified that the proposed method is superior to other state-of-the-art examinations. This study contributes to the advancement of the rapid detection of ischemic stroke, shedding light on the untapped potential of EEG and demonstrating the efficacy of deep learning in ischemic stroke identification.