Acute Phase Of Stroke Research Articles

Effects of edaravone dexborneol on functional outcome and inflammatory response in patients with acute ischemic stroke

BackgroundEdaravone dexborneol has been reported as an effective neuroprotective agent in the treatment of acute ischemic stroke (AIS). This study aimed at investigating the impact of edaravone dexborneol on functional outcomes and systematic inflammatory response in AIS patient.MethodsAll participants were recruited from the AISRNA study (registered 21/11/2019, NCT04175691 [ClinicalTrials.gov]) between January 2022 and December 2022. The AIS patients were divided into two groups based on whether they received the treatment of edaravone dexborneol (37.5 mg/12 hours, IV) within 48 h after stroke onset. Inflammatory response was determined by detecting levels of cytokines (interleukin-2 [IL-2], IL-4, IL-5, IL-8, IL-6, IL-10, IL-12p70, IL-17, tumor necrosis factor-α [TNF-α], interferon-γ [IFN-γ], IFN-α, and IL-1β) within 14 days after stroke onset.ResultsEighty-five AIS patients were included from the AISRNA study. Patients treated with edaravone dexborneol showed a significantly higher proportion of modified Rankin Scale score < 2 compared to those who did not receive this treatment (70.7% versus 47.8%; P = 0.031). Furthermore, individuals receiving edaravone dexborneol injection exhibited lower expression levels of interleukin (IL)-1β, IL-6, and IL-17, along with higher levels of IL-4 and IL-10 expression during the acute phase of ischemic stroke (P < 0.05). These trends were not observed for IL-2, IL-5, IL-8, IL-12p70, tumor necrosis factor-α, interferon-γ [IFN-γ], and IFN-α (P > 0.05).ConclusionsTreatment with edaravone dexborneol resulted in a favorable functional outcome at 90 days post-stroke onset when compared to patients without this intervention; it also suppressed proinflammatory factors expression while increasing anti-inflammatory factors levels.Trial registrationClinicalTrials.gov NCT04175691. Registered November 21, 2019, https://www.clinicaltrials.gov/ct2/show/NCT04175691.

Epidemiological, Clinical and Radiological Profiles of Post-stroke Aphasia in Neurology in Abidjan from April to September 2022

Background and purpose: Aphasia is a language disorder that frequently occurs after a cerebrovascular accident. This prospective descriptive study aimed to describe the epidemiological, clinical and radiological profiles of post-stroke aphasia. Materials and method: Patients presenting aphasia after a stroke documented by brain imaging, hospitalized from April to September 2022 in the neurology departments of the Cocody and Treichville University Hospitals were included. Aphasia was screened using the Language Screening Test (LAST). Epidemiological, clinical and radiological data were collected through clinical observation. Results: Of the 217 stroke patients admitted to neurology during the period, 32 presented aphasia (14.7%). The average age was 56 years, with a male predominance (M/F sex ratio of 2.2). The majority of patients had primary or no schooling (87.5%). Arterial hypertension was the most frequent cardiovascular risk factor (50%) and hemiplegia, the most common physical sign (93.8%). The average LAST score for aphasic patients was 5.3 out of 15. We observed that naming and repetition were the most affected components of speaking, with scores below normal in 87.5%. and 88% of cases. Regarding oral comprehension, order execution was the component most affected for 75.1% of patients. In the acute phase of stroke, 50% of cases of aphasia were severe. Radiologically, 75% of patients presented an ischemic stroke with the predilection of the middle cerebral artery. Conclusion: this study highlights the importance of early detection of aphasia in post-stroke patients and rapid treatment to optimize their linguistic recovery.

Delayed plasma kallikrein inhibition fosters post-stroke recovery by reducing thrombo-inflammation

Activation of the kallikrein-kinin system promotes vascular leakage, inflammation, and neurodegeneration in ischemic stroke. Inhibition of plasma kallikrein (PK) – a key component of the KKS – in the acute phase of ischemic stroke has been reported to reduce thrombosis, inflammation, and damage to the blood-brain barrier. However, the role of PK during the recovery phase after cerebral ischemia is unknown. To this end, we evaluated the effect of subacute PK inhibition starting from day 3 on the recovery process after transient middle artery occlusion (tMCAO). Our study demonstrated a protective effect of PK inhibition by reducing infarct volume and improving functional outcome at day 7 after tMCAO. In addition, we observed reduced thrombus formation in cerebral microvessels, fewer infiltrated immune cells, and an improvement in blood-brain barrier integrity. This protective effect was facilitated by promoting tight junction reintegration, reducing detrimental matrix metalloproteinases, and upregulating regenerative angiogenic markers. Our findings suggest that PK inhibition in the subacute phase might be a promising approach to accelerate the post-stroke recovery process.

Low phase angle is associated with swallowing outcomes in patients with acute stroke

Background and purposeStroke-induced dysphagia is a critical complication that can lead to severe secondary worldwide health issues. This retrospective cohort study investigated the association between phase angle (PhA) and swallowing function in the acute phase of stroke. We aim to establish whether nutritional and muscular interventions associated with PhA could enhance swallowing recovery and reduce related risks post-stroke. MethodsStroke patients requiring rehabilitation were assessed for the association between low PhA—with cutoff values for low PhA defined as less than 5.28 for men and 4.32 for women—and swallowing function using a functional oral intake scale (FOIS) on Day 7 after admission and after the completion of acute stroke treatment. ResultsIn this study of 140 acute stroke patients (median age 74[69–81], and 85 men and 55 women), 76 patients with low PhA significantly exhibited older age, lower body mass index, more decline in skeletal muscle mass index, and lower premorbid modified Rankin Scale scores compared to 64 patients with high PhA. Multivariate linear regression revealed that low PhA was independently associated with FOIS scores on Day 7 after admission (β=-0.143 and p=0.036) and after the completion of acute stroke treatment (β=-0.513 and p=0.024), even when adjusting for confounding factors. ConclusionsLow PhA is associated with swallowing function in patients with acute stroke. Nutritional and physical interventions improving PhA may lead to a reduction of the risk associated with stroke sequelae.

Establishing minimal clinically important differences and cut-off values for the lower limb motricity index and trunk control test in older patients with acute stroke: a prospective cohort study

ABSTRACT Objective To establish the Minimal Clinically Important Differences (MCIDs) for lower limb strength measured by the Motricity Index (LLMI) and trunk function assessed by the Trunk Control Test (TCT) in the acute phase of stroke in older patients. Further, the study sought to determine the cutoff values predicting functional prognosis at discharge for both the LLMI and TCT. Methods This prospective cohort study was conducted for older patients (≥65 years) admitted for acute stroke, receiving guideline-based stroke care that includes early rehabilitation. The LLMI and TCT were measured within 7 days of admission and at discharge. The MCID was derived from receiving operating characteristic curves, based on a ≥ 1 point shift in the modified Rankin Scale (mRS) from admission to discharge. A good functional prognosis at discharge was defined as an mRS score of ≤ 3. Results A total of 201 older patients with acute stroke were included. The TCT achieved an MCID of 13 (area under the curve [AUC] = 0.704, 95% confidence interval [CI]: 0.633–0.775), whereas the LLMI lacked the precision to produce a significant MCID. The optimal cutoff points for predicting a good outcome were found to be an LLMI score of 65 (AUC = 0.770, 95% CI: 0.705–0.835) and a TCT score of 25 (AUC = 0.827, 95% CI: 0.768–0.887) upon admission. Conclusions This study identified a valid MCID for the TCT, failed to do so for the LLMI, and established cutoff values for both the LLMI and TCT that can predict good outcomes in older patients with acute stroke.

Pathophysiology, Diagnosis, Prognosis, and Prevention of Poststroke Epilepsy: Clinical and Research Implications.

Poststroke epilepsy (PSE) is associated with higher mortality and poor functional and cognitive outcomes in patients with stroke. With the remarkable development of acute stroke treatment, there is a growing number of survivors with PSE. Although approximately 10% of patients with stroke develop PSE, given the significant burden of stroke worldwide, PSE is a significant problem in stroke survivors. Therefore, the attention of health policymakers and significant funding are required to promote PSE prevention research. The current PSE definition includes unprovoked seizures occurring more than 7 days after stroke onset, given the high recurrence risks of seizures. However, the pathologic cascade of stroke is not uniform, indicating the need for a tissue-based approach rather than a time-based one to distinguish early seizures from late seizures. EEG is a commonly used tool in the diagnostic work-up of PSE. EEG findings during the acute phase of stroke can potentially stratify the risk of subsequent seizures and predict the development of poststroke epileptogenesis. Recent reports suggest that cortical superficial siderosis, which may be involved in epileptogenesis, is a promising marker for PSE. By incorporating such markers, future risk-scoring models could guide treatment strategies, particularly for the primary prophylaxis of PSE. To date, drugs that prevent poststroke epileptogenesis are lacking. The primary challenge involves the substantial cost burden due to the difficulty of reliably enrolling patients who develop PSE. There is, therefore, a critical need to determine reliable biomarkers for PSE. The goal is to be able to use them for trial enrichment and as a surrogate outcome measure for epileptogenesis. Moreover, seizure prophylaxis is essential to prevent functional and cognitive decline in stroke survivors. Further elucidation of factors that contribute to poststroke epileptogenesis is eagerly awaited. Meanwhile, the regimen of antiseizure medications should be based on individual cardiovascular risk, psychosomatic comorbidities, and concomitant medications. This review summarizes the current understanding of poststroke epileptogenesis, its risks, prognostic models, prophylaxis, and strategies for secondary prevention of seizures and suggests strategies to advance research on PSE.

Nursing care for a 71-year-old patient suffering from the acute phase of ischemic stroke

Nursing care for a 71-year-old patient suffering from the acute phase of ischemic stroke

Blood pressure variability at rest and during pressor challenges in patients with acute ischemic stroke.

Patients with acute ischemic stroke (AIS) have elevated blood pressure (BP) variability (BPV) and reduced baroreflex sensitivity (BRS) at rest for several days after initial stroke symptoms. We aimed to assess BPV and BRS in AIS patients during pressor challenge maneuvers in the acute and subacute phases of stroke. Pressor challenge maneuvers simulate day-to-day activities and can predict the quality of life. Continuous beat-to-beat BP and ECG in 15 AIS patients (mean age 69 ± 7.5 years) and 15 healthy controls (57 ± 16 years) were recorded at rest and during a 5-min rapid head positioning (RHP) paradigm. Patients were assessed within 24 h (acute phase) and 7 days (subacute phase) of stroke onset. Low frequency (LF) SBP power (measure of BPV), LF-α, and combined α-index (measure of BRS) were calculated from the recordings. In the acute phase, at rest, LF-SBP power was higher ( P = 0.024) and α-index was lower ( P = 0.006) in AIS patients than in healthy controls. There was no change in LF-SBP during RHP in the patients but in healthy controls, it increased significantly ( P = 0.018). In the subacute phase, at rest, the alpha-index increased ( P = 0.037) and LF-SBP decreased ( P = 0.029) significantly in the AIS patients, however, there was still no rise in the LF-SBP power during RHP ( P = 0.240). AIS patients have a high resting BPV. High resting BPV may be responsible for blunted BPV responses during pressor challenge maneuvers such as RHP, suggesting ongoing autonomic dysfunction and compromised quality of life.

Communicating Arteries and Leptomeningeal Collaterals: A Synergistic but Independent Effect on Patient Outcomes after Stroke.

The collateral system is a compensatory mechanism activated in the acute phase of an ischemic stroke. It increases brain perfusion to the hypoperfused area. Arteries of the Willis' circle supply antegrade blood flow, while pial (leptomeningeal) arteries direct blood via retrograde flow. The aim of our retrospective study was to investigate the relationship between both collateral systems, computed tomography perfusion (CTP) values, and functional outcomes in acute stroke patients. Overall, 158 patients with anterior circulation stroke who underwent mechanical thrombectomy were included in the study. We analyzed the presence of communicating arteries and leptomeningeal arteries on computed tomography angiography. Patients were divided into three groups according to their collateral status. The main outcomes were the rate of functional independence 3 months after stroke (modified Rankin scale score, mRS) and mortality rate. Our study suggests that the collateral status, as indicated by the three groups (unfavorable, intermediate, and favorable), is linked to CT perfusion parameters, potential recuperation ratio, and stroke outcomes. Patients with favorable collateral status exhibited smaller core infarct and penumbra volumes, higher mismatch ratios, better potential for recuperation, and improved functional outcomes compared to patients with unfavorable or intermediate collateral status.

Alterations of tau and Camk2 in acute stroke and effects of a multicomponent drug

Abstract Background Stroke is one of the leading causes of death around the world. The sequelae of ischemic stroke cause drastic effects on the quality of life for patients. Sanwujiaowan (SWJW) is a mixture prepared with 5 herbal medicines (Aconiti Lateralis Radix Praeparata, Aconiti Kusnezoffii Radix, Polygoni Multiflori Radix, Aconiti Radix, and Olibanum), with a long history of application in treating the sequelae of stroke. Objectives To provide evidence and decipher the mechanism of SWJW in alleviating stroke. Materials and Methods In this article, we expanded the indicators of SWJW by an integrated strategy based on signature metabolomics, target proteins, and bioinformatics and probed into the mechanism of SWJW intervention in ischemic stroke in a rat model. Results The results indicated that SWJW protected rats from nerve damage during the acute phase of ischemic stroke by regulating tau phosphorylation via the PI3K/Akt pathway. Conclusions This study, for the first time, proved that the reduction of phosphorylated tau was harmful for the neural function in the acute phase of ischemic stroke. Meanwhile, the pathological changes of phosphorylated tau proteins were detected in stroke and recalled by SWJW. This finding may provide a new reference for formulating treatment strategies for the acute phase of ischemic stroke.

Anti-ferroptosis exosomes engineered for targeting M2 microglia to improve neurological function in ischemic stroke.

Stroke is a devastating disease affecting populations worldwide and is the primary cause of long-term disability. The inflammatory storm plays a crucial role in the progression of stroke. In the acute phase of ischemic stroke, there is a transient increase in anti-inflammatory M2 microglia followed by a rapid decline. Due to the abundant phospholipid in brain tissue, lipid peroxidation is a notable characteristic of ischemia/reperfusion (I/R), constituting a structural foundation for ferroptosis in M2 microglia. Slowing down the decrease in M2 microglia numbers and controlling the inflammatory microenvironment holds significant potential for enhancing stroke recovery. We found that the ferroptosis inhibitor can modulate inflammatory response in MCAO mice, characterizing that the level of M2 microglia-related cytokines was increased. We then confirmed that different subtypes of microglia exhibit distinct sensitivities to I/R-induced ferroptosis. Adipose-derived stem cells derived exosome (ADSC-Exo) effectively decreased the susceptibility of M2 microglia to ferroptosis via Fxr2/Atf3/Slc7a11, suppressing the inflammatory microenvironment and promoting neuronal survival. Furthermore, through plasmid engineering, a more efficient M2 microglia-targeted exosome, termed M2pep-ADSC-Exo, was developed. In vivo and in vitro experiments demonstrated that M2pep-ADSC-Exo exhibits significant targeting specificity for M2 microglia, further inhibiting M2 microglia ferroptosis and improving neurological function in ischemic stroke mice. Collectively, we illustrated a novel potential therapeutic mechanism that Fxr2 in ADSC-Exo could alleviate the M2 microglia ferroptosis via regulating Atf3/Slc7all expression, hence inhibiting the inflammatory microenvironment, improving neurofunction recovery in cerebral I/R injury. We obtained a novel exosome, M2pep-ADSC-Exo, through engineered modification, which exhibits improved targeting capabilities toward M2 microglia. This provides a new avenue for the treatment of stroke.

Post-stroke cognitive impairment: exploring molecular mechanisms and omics biomarkers for early identification and intervention

Post-stroke cognitive impairment (PSCI) is a major stroke consequence that has a severe impact on patients’ quality of life and survival rate. For this reason, it is especially crucial to identify and intervene early in high-risk groups during the acute phase of stroke. Currently, there are no reliable and efficient techniques for the early diagnosis, appropriate evaluation, or prognostication of PSCI. Instead, plenty of biomarkers in stroke patients have progressively been linked to cognitive impairment in recent years. High-throughput omics techniques that generate large amounts of data and process it to a high quality have been used to screen and identify biomarkers of PSCI in order to investigate the molecular mechanisms of the disease. These techniques include metabolomics, which explores dynamic changes in the organism, gut microbiomics, which studies host–microbe interactions, genomics, which elucidates deeper disease mechanisms, transcriptomics and proteomics, which describe gene expression and regulation. We looked through electronic databases like PubMed, the Cochrane Library, Embase, Web of Science, and common databases for each omics to find biomarkers that might be connected to the pathophysiology of PSCI. As all, we found 34 studies: 14 in the field of metabolomics, 5 in the field of gut microbiomics, 5 in the field of genomics, 4 in the field of transcriptomics, and 7 in the field of proteomics. We discovered that neuroinflammation, oxidative stress, and atherosclerosis may be the primary causes of PSCI development, and that metabolomics may play a role in the molecular mechanisms of PSCI. In this study, we summarized the existing issues across omics technologies and discuss the latest discoveries of PSCI biomarkers in the context of omics, with the goal of investigating the molecular causes of post-stroke cognitive impairment. We also discuss the potential therapeutic utility of omics platforms for PSCI mechanisms, diagnosis, and intervention in order to promote the area’s advancement towards precision PSCI treatment.

Role of histone deacetylases and sirtuins in the ischaemic stroke: a protocol for a systematic review and meta-analysis of animal studies

BackgroundStroke is a major cause of global mortality and disability. Currently, the treatment of acute ischaemic stroke through reperfusion has posed several challenges, raising the need for complementary options to...

How Clot Composition Influences Fibrinolysis in the Acute Phase of Stroke: A Proteomic Study of Cerebral Thrombi.

The dramatic clinical improvement offered by mechanical thrombectomy raised questions about the relevance of prior intravenous thrombolysis in large-vessel occlusion strokes. Hence, studying intravenous thrombolysis susceptibility and its dependence on thrombus composition is crucial. We used an observational proteomic study of whole thrombi retrieved by mechanical thrombectomy to identify factors associated with fibrin content and fibrinolytic activity (FA). In 104 stroke patients, the thrombi proteome was established by mass spectrometry coupled to liquid chromatography. FA was estimated in clots both outside (FAout) by measuring D-dimer levels at the blood-thrombus interface and inside (FAin) by evaluating the ratio of fibrinogen α to its plasmin-cleaved forms using proteomics coupled with protein electrophoresis. The factors associated with fibrin content, FAin, and FAout were determined by intravenous thrombolysis-adjusted linear regression. FAout (P<0.0001) and FAin (P=0.0147) were driven by recombinant tissue-type plasminogen activator (r-tPA) administration (47/104) and thrombus composition. Indeed, FAout was greater with fibrin-rich than erythrocyte-rich thrombi, presumably because of more (r)tPA substrates. Thus, FAout was increased with cardioembolic thrombi (72/104), which are rich in fibrin (P=0.0300). Opposite results were found inside the thrombus, suggesting that (r)tPA penetrability was hampered by the density of the fibrinous cap. Moreover, blood cells had a strong impact on thrombus structure and susceptibility to (r)tPA. Indeed, fibrin content was negatively associated with erythrocyte-specific proteins in the thrombus, admission hematocrit (P=0.0139), and hemoglobin level (P=0.0080), which underlines the key role of erythrocytes in thrombus composition. Also, an increased number of neutrophils impaired FAout (P=0.0225), which suggests that their aggregation around the thrombus prevented the (r)tPA attack. Only FAout was significantly associated with reduced thrombus weight (P=0.0310), increased recanalization rate (P=0.0150), good clinical outcome (P=0.0480), and reduced mortality (P=0.0080). Proteomics can offer new insights into the close relationship between thrombus composition and susceptibility to fibrinolysis, paving the way for new adjuvant therapies.

Longitudinal neuropsychological performance of post-stroke adults with and without rehabilitation

This study compared the neuropsychological performance of two post-stroke groups, one undergoing rehabilitation and the other not receiving any intervention, on the acute and chronic stroke phases, and explored sociodemographic and neurological variables associated with changes in performance over time. Sixty-three adults underwent neuropsychological assessment with the Cognitive Screening Instrument (TRIACOG) less than thirty days after having a stroke and were reassessed three to six months after stroke. Thirty-eight participants did not undertake rehabilitation and twenty-five did physiotherapy and/or speech therapy between the two time points. The frequency of cognitive deficits (between groups) and the range of cognitive assessment scores over time (between and within groups) were analyzed. There was a significant decrease in the frequency of neuropsychological deficits and improvement on neuropsychological assessment scores over time only in the group undergoing rehabilitation. Severity of the neurological condition, years of education and being in rehabilitation explained the longitudinal changes in several cognitive domains measured by TRIACOG. Engaging in rehabilitation within three to six months post-stroke is crucial for enhancing the recovery of neuropsychological deficits. Cognitive screening instruments like TRIACOG can be used by health professionals to identify stroke-related neuropsychological changes and plan interventions.

Validity and Reliability of the Swedish Version of the Gugging Swallowing Screen for use in Acute Stroke Care.

The purpose of this study was to cross-culturally validate the Swedish version of the Gugging Swallowing Screen (GUSS-S) for use in the acute phase of stroke. Further, to evaluate the inter-rater reliability between different healthcare professionals. GUSS was translated into Swedish using a forward-backward method followed by expert rating to obtain content validity. For criterion validity, the GUSS-S score was compared with Flexible Endoscopic Evaluation of Swallowing (FEES) assessed with the Penetration-Aspiration Scale (PAS) in acute stroke patients (≤ 96h after stroke onset). Convergent validity was calculated by comparison with the Functional Oral Intake Scale (FOIS) as per the comprehensive FEES assessment, the Standardized Swallowing Assessment (SSA), and the National Institutes of Health Stroke Scale (NIHSS). To evaluate inter-rater reliability, a nurse and a speech-language pathologist (SLP) independently assessed 30 patients. In total, 80 patients (32 women, median age 77 years (range 29-93) were included, mean 1.7 ± 0.9 days after admission. With a cut-off value of 14 points, the GUSS-S identified aspiration with a sensitivity of 100% and a specificity of 73% (area under the curve: 0.87, 95% CI 0.78-0.95). Spearman rank correlation showed very strong correlation between the GUSS-S and PAS (rs=-0.718, P = < 0.001) and FOIS (rs=0.720, P = 0.001) and strong correlation between the GUSS-S and SSA (rs=0.545, P = < 0.001) and NIHSS (rs=-0.447, P = 0.001). The inter-rater agreement for GUSS-S was substantial (Kw=0.67, P = < 0.001). The results indicate that the GUSS-S is a valid and reliable tool for the assessment of dysphagia in acute stroke patients by different healthcare professionals.

Acupuncture modulates the AMPK/PGC-1 signaling pathway to facilitate mitochondrial biogenesis and neural recovery in ischemic stroke rats.

The main objective of this study was to investigate the role and mechanism of acupuncture on anti-nerve injury in the acute phase by regulating mitochondrial energy metabolism via monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) axis in rat ischemic stroke. Middle cerebral artery occlusion (MCAO) was established by middle cerebral artery occlusion/reperfusion. One-week of acupuncture was performed during the acute phase of ischemic stroke. The neurological function and brain tissue integrity were evaluated. Mitochondrial function (intracellular ATP level and the activity of mitochondrial respiratory chain complex I) and the level of NADH oxidase (NOX) were detected by enzymatic chemistry. Next, the potential molecular mechanisms were explored by western blotting, fluorescence quantitative PCR and immunohistochemistry method. (1) Acupuncture treatment for MCAO/R rats showed a significant improvement in the infarcted tissue accompanied by functional recovery in Zea-Longa score and balance beam score outcomes, motor function performances. (2) Acupuncture increased the levels of ATP and mitochondrial respiratory chain complex I, decreased the NOX levels in cerebral ischemia established by suture-occluded method. (3) Acupuncture reduced the necrosis dissolution of neuronal cells and meningeal edema, while promoting angiogenesis. (4) Quantitative immunohistochemical staining results showed acupuncture can increase the expression of AMPK, p-AMPK and the mitochondrial transcription factor PGC-1α, NRF2, TFAM and uncoupling protein 2 (UCP2). Meanwhile, acupuncture treatment up-regulated the expression of the corresponding protein. (5) Subsequently, acupuncture enhanced AMPK phosphorylation as well as the expression of PGC-1α, NRF2, TFAM and UCP2, implicated in mitochondrial synthesis and cellular apoptosis. (6) Finally, injections of AMPK antagonists and activators confirmed AMPK as a therapeutic target for the anti-nerve damage effects of acupuncture. Acupuncture intervention relieved ischemic stroke progression in MCAO rats by promoting energy metabolism and mitochondrial biogenesis in the brain and alleviating neuronal apoptosis, which was mediated by eliciting AMPK/PGC-1α axis, among them AMPK is a therapeutic target.

The Usefulness of Factor XIII Concentration Assessment in Patients in the Acute Phase of Ischaemic Stroke Treated with Thrombolysis.

In recent years, there has been a growing interest in factor XIII in ischaemic stroke. The study's main aim was to assess the usefulness of factor XIII concentration determination in patients with acute ischaemic stroke (AIS) treated with thrombolysis with recombinant tissue plasminogen activator (t-PA). The study was conducted in two groups of 84 patients with AIS: group I-with thrombolytic therapy and group II-without thrombolysis. A physical examination, neurological status (using the National Institutes of Health Stroke Scale, NIHSS), daily patients' activities measured with the Barthel Index and Modified Rankin Scale (mRS), and blood parameters were conducted on day 1 and day 7. The following parameters were assessed: highly sensitive C-reaction protein (CRP), fibrinogen, D-dimers (DD), neutrophil-lymphocyte ratio (NLR index), and the concentration of factor XIII-A. In group I, the concentration of XIII-A decreased significantly between day 1 and 7 (p < 0.001). In group I, the concentration of XIII-A on day 7 in Total Anterior Circulation Infarct (TACI) was significantly lower than in non-TACI stroke. XIII-A concentration in group I was significantly lower in patients < 31 points with Acute Stroke Registry and Analysis of Lausanne (ASTRAL). A greater decrease in XIII-A between the first sampling on day 1 and the second sampling on day 7 was associated with a worse patient neurological state in group I. In patients with AIS treated with t-PA, factor XIII concentrations decrease in the acute phase of stroke, and the largest decrease occurs in the TACI stroke. Determination of factor XIII concentration in patients with AIS can be used in clinical practice as an additional parameter supporting the assessment of stroke severity and may play a role in the prognosis; lower factor XIII-A activity may be a predictor of a worse prognosis.

Transcriptome Analysis Reveals Dynamic Microglial-Induced A1 Astrocyte Reactivity via C3/C3aR/NF-κB Signaling After Ischemic Stroke.

Microglia and astrocytes are key players in neuroinflammation and ischemic stroke. A1 astrocytes are a subtype of astrocytes that are extremely neurotoxic and quickly kill neurons. Although the detrimental A1 astrocytes are present in many neurodegenerative diseases and are considered to accelerate neurodegeneration, their role in the pathophysiology of ischemic stroke is poorly understood. Here, we combined RNA-seq, molecular and immunological techniques, and behavioral tests to investigate the role of A1 astrocytes in the pathophysiology of ischemic stroke. We found that astrocyte phenotypes change from a beneficial A2 type in the acute phase to a detrimental A1 type in the chronic phase following ischemic stroke. The activated microglial IL1α, TNF, and C1q prompt commitment of A1 astrocytes. Inhibition of A1 astrocytes induction attenuates reactive gliosis and ameliorates morphological and functional defects following ischemic stroke. The crosstalk between astrocytic C3 and microglial C3aR contributes to the formation of A1 astrocytes and morphological and functional defects. In addition, NF-κB is activated following ischemic stroke and governs the formation of A1 astrocytes via direct targeting of inflammatory cytokines and chemokines. Taken together, we discovered that A2 astrocytes and A1 astrocytes are enriched in the acute and chronic phases of ischemic stroke respectively, and that the C3/C3aR/NF-κB signaling leads to A1 astrocytes induction. Therefore, the C3/C3aR/NF-κB signaling is a novel therapeutic target for ischemic stroke treatment.

Circulating HMGB1 in acute ischemic stroke and its association with post-stroke cognitive impairment.

Ischemic stroke frequently leads to a condition known as post-stroke cognitive impairment (PSCI). Timely recognition of individuals susceptible to developing PSCI could facilitate the implementation of personalized strategies to mitigate cognitive deterioration. High mobility group box 1 (HMGB1) is a protein released by ischemic neurons and implicated in inflammation after stroke. Circulating levels of HMGB1 could potentially serve as a prognostic indicator for the onset of cognitive impairment following ischemic stroke. To investigate the predictive value of circulating HMGB1 concentrations in the acute phase of ischemic stroke for the development of cognitive dysfunction at the 3-month follow-up. A total of 192 individuals experiencing their initial episode of acute cerebral infarction were prospectively recruited for this longitudinal investigation. Concentrations of circulating HMGB1 were quantified using an enzyme-linked immunosorbent assay (ELISA) technique within the first 24 hours following hospital admission. Patients underwent neurological evaluation including NIHSS scoring. Neuropsychological evaluation was conducted at the 3-month follow-up after the cerebrovascular event, employing the Montreal Cognitive Assessment (MoCA) as the primary tool for assessing cognitive performance. Multivariable logistic regression models were employed to investigate the relationship between circulating HMGB1 concentrations and cognitive dysfunction following stroke, which was operationalized as a MoCA score below 26, while controlling for potential confounders including demographic characteristics, stroke severity, vascular risk factors, and laboratory parameters. Of 192 patients, 84 (44%) developed PSCI. Circulating HMGB1 concentrations were significantly elevated in individuals who developed cognitive dysfunction following stroke compared to those who maintained cognitive integrity (8.4 ±1.2 ng/mL vs 4.6 ±0.5 ng/mL, respectively; p<0.001). The prevalence of PSCI showed a dose-dependent increase with higher HMGB1 quartiles. After controlling for potential confounders such as demographic factors (age, gender, and education), stroke severity, vascular risk factors, and laboratory parameters in a multivariable logistic regression model, circulating HMGB1 concentrations emerged as a significant independent predictor of cognitive dysfunction following stroke (regression coefficient = 0.236, p<0.001). Circulating HMGB1 concentrations quantified within the first 24 hours following acute cerebral infarction are significantly and independently correlated with the likelihood of developing cognitive dysfunction at the 3-month follow-up, even after accounting for potential confounding factors. HMGB1 may be a novel biomarker to identify patients likely to develop post-stroke cognitive impairment for targeted preventive interventions.