Ischemic Stroke Research Articles

Reader Response: Statin Therapy for Secondary Prevention in Ischemic Stroke Patients With Cerebral Microbleeds.

Reader Response: Statin Therapy for Secondary Prevention in Ischemic Stroke Patients With Cerebral Microbleeds.

Relationship Between DWI-Based Acute Ischemic Stroke Volume, Location and Severity of Dysphagia

Background/Objectives: The impact of stroke location and volume on the development of post-stroke dysphagia is not fully understood. The aim of this study is to evaluate the relationship between acute ischemic lesions and the severity of dysphagia. Methods: Brain MRIs were obtained with a 1.5 Tesla MRI system (Magnetom Avanto B13, Siemens, Erlangen, Germany). The brain MRI protocol included axial echo planar diffusion-weighted imaging (DWI). The acute ischemic volume was obtained using DWI by drawing regions of interest (ROIs). The diagnosis and assessment of the severity of dysphagia was carried out by a multidisciplinary team and included the Dysphagia Outcome and Severity Scale (DOSS), the Penetration–Aspiration Scale (PAS), and the Pooling score (P-score). The threshold for statistical significance was set at 5%. Results: Among all the patients enrolled (n = 64), 28 (43.8%) were males and 36 (56.2%) were females, with a mean age of 78.8 years. Thirty-three (51.6%) of them had mild dysphagia and thirty-one (48.4%) had moderate–severe dysphagia. The total ischemic volume was negatively correlated with the DOSS (r = −0.441, p = 0.0003) and positively with the P-score (rs = 0.3054, p = 0.0328). Conclusions: There are significant associations between the severity of dysphagia and the quantitative DWI-based data of the acute ischemic volume and anatomical location.

Editors' Note: Statin Therapy for Secondary Prevention in Ischemic Stroke Patients With Cerebral Microbleeds.

Editors' Note: Statin Therapy for Secondary Prevention in Ischemic Stroke Patients With Cerebral Microbleeds.

Evaluation of Door-to-Needle Times Between Alteplase and Tenecteplase for Acute Ischemic Stroke at Two Academic Medical Centers.

Off-label tenecteplase use for acute ischemic stroke (AIS) has increased due to ease of administration and comparable efficacy and safety to alteplase. This study aimed to evaluate time to thrombolysis before and after transition from alteplase to tenecteplase for treatment of AIS at 2 institutions. This retrospective cohort study included adult patients receiving thrombolysis for AIS before and after transition from alteplase to tenecteplase at 2 academic medical centers from January 1, 2020 to January 31, 2024. The primary endpoint was door-to-needle (DTN) time, defined as minutes from hospital arrival to thrombolysis administration. Notable secondary endpoints included time from last known well (LKW) to thrombolysis, time from brain imaging to thrombolysis, hospital length of stay (LOS), and incidence of symptomatic intracranial hemorrhage (sICH). A total of 328 patients (168 tenecteplase and 160 alteplase) were included. Patients were 51.5% female with a median (interquartile range [IQR]) age of 70 [58-80] years and initial National Institutes of Health Stroke Scale (NIHSS) score of 8 [5-14]. There was no statistically significant difference in DTN time (60 vs 56 minutes), time from LKW to thrombolysis (134 vs 147.5 minutes), or time from brain imaging to thrombolysis (32 vs 31 minutes) between tenecteplase and alteplase. Hospital LOS (5.7 vs 4.9 days) and the rates of sICH (3% vs 3.8%) were similar between groups. Tenecteplase and alteplase had comparable DTN times for treatment of AIS and similar safety endpoints. Further studies are warranted to identify opportunities to streamline DTN times with tenecteplase.

Current Stroke Solutions Using Artificial Intelligence: A Review of the Literature

Introduction: In recent years, artificial intelligence (AI) has emerged as a transformative tool for enhancing stroke diagnosis, aiding treatment decision making, and improving overall patient care. Leading AI-driven platforms such as RapidAI, Brainomix®, and Viz.ai have been developed to assist healthcare professionals in the swift and accurate assessment of stroke patients. Methods: Following the PRISMA guidelines, a comprehensive systematic review was conducted using PubMed, Embase, Web of Science, and Scopus. Characteristic descriptive measures were gathered as appropriate from all included studies, including the sensitivity, specificity, accuracy, and comparison of the available tools. Results: A total of 31 studies were included, of which 29 studies focused on detecting acute ischemic stroke (AIS) or large vessel occlusions (LVOs), and 2 studies focused on hemorrhagic strokes. The four main tools used were Viz.ai, RapidAI, Brainomix®, and deep learning modules. Conclusions: AI tools in the treatment of stroke have demonstrated usefulness for diagnosing different stroke types, providing high levels of accuracy and helping to make quicker and more precise clinical judgments.

Stress hyperglycemia is associated with early neurologic deterioration in patients with acute ischemic stroke after intravenous thrombolysis without hemorrhagic transformation.

This aimed to elucidate the impact of stress hyperglycemia on early neurological deterioration (END) in patients with acute non-cardiogenic cerebral infarction who did not experience hemorrhagic transformation following intravenous thrombolysis to identify risk factors associated with END. This retrospective case-control study analyzed data from consecutive patients who received intravenous thrombolysis for acute ischemic stroke (AIS) without hemorrhagic transformation at the Stroke Center of The Fifth Affiliated Hospital of Sun Yat-sen University from January 2018 to February 2023. END was defined as an increase of more than 2 points on the National Institutes of Health Stroke Scale (NIHSS) within 7 days of admission. A total of 250 patients (56 males, 22.4%) were included, with a mean age of 63.34 ± 12.90 years. Of them, 41 were classified into the END group and 209 into the non-END group. Stress hyperglycemia ratio (SHR) demonstrated a significant correlation with END (r=-0.003, P = 0.003). HbA1c (OR = 0.68, 95% CI: 0.481-0.921) and SHR (OR = 0.00, 95% CI: 0.0-0.051) were independently associated with END. Receiver-operating characteristic (ROC) curve analysis indicated that SHR had a sensitivity of 79.9%, specificity of 88.8%, and an area under the curve (AUC) of 0.857 for predicting END. SHR was significantly associated with END in patients with acute non-cardioembolic cerebral infarction who did not undergo hemorrhagic transformation after intravenous thrombolysis.

Od laboratorium do kliniki: eksperymentalne modele zwierzęce w badaniach nad udarem niedokrwiennym mózgu

Stroke is a devastating cardiovascular disease with a high mortality rate, leading to a significant reduction in quality of life and life expectancy. Due to the complexity of the pathophysiological processes following stroke in humans, the use of animal models of stroke, in particular rodent models, is essential for the development of treatments for patients. Transient or permanent middle cerebral artery occlusion (MCAo) and photothrombotic models are the most commonly used to simulate ischemic stroke and are discussed in this review in detail. Furthermore, we provide an overview of the current knowledge on the inflammatory and regenerative responses to stroke, executed mainly by glial cells but also by macrophages infiltrating the post-ischemic brain. Understanding the advantages and disadvantages of different animal models is the basis for their further refinement, allowing for better simulation of post-stroke events and the development of new therapeutic approaches for cerebral ischemia in humans.

Effect of Hemoglobin and Blood Glucose Levels on CT Perfusion Ischemic Core Estimation: A Post Hoc Analysis of the ESCAPE-NA1 Trial.

CT perfusion (CTP) maps can estimate the ischemic core in acute ischemic stroke based on distinctive cerebral blood flow thresholds. However, metabolic factors beyond perfusion influence the tissue tolerance to ischemia and the infarct growth rate. Underestimating the ischemic core volume (ICV) might result in overestimating the salvageable cerebral tissue and, consequently, overestimating the potential clinical benefits of reperfusion therapies. We aim to evaluate whether baseline hemoglobin and blood glucose levels influence the accuracy of baseline CTP ICV estimations. Large vessel occlusion stroke patients investigated with baseline CTP undergoing thrombectomy with near-complete reperfusion and without parenchymal hemorrhage from the ESCAPE-NA1 trial were included. Patients were subdivided into anemic (hemoglobin <130 g/L for men and <120 g/L for women) and nonanemic groups, and hyperglycemic (blood glucose level >7 mmol/L) and normoglycemic groups. Ischemic core underestimated volume (ICuV) was calculated: final infarct volume minus CTP-based ICV. The primary outcome was the presence of "perfusion scotoma" defined as ICuV ≥10 mL. Presence of "perfusion scotoma" and median ICuV were compared between anemic vs nonanemic and hyperglycemic vs normoglycemic patients using nonparametric tests and multivariable binary logistic regression with adjustment for baseline variables. One hundred sixty-two of 1,105 (15%) patients were included (median age 70.5 [interquartile range (IQR) 61-80.4], 50.6% women). The median ICuV was 7.26 mL (IQR 0-25.63). Seventy-eight (48%) patients demonstrated perfusion scotoma. Forty-two (25.7%) patients were anemic, and 65 (40.1%) were hyperglycemic. In univariable analysis, the hyperglycemic group had a higher prevalence of perfusion scotoma (65% [n = 40] vs 39% [n = 38], p = 0.006) and larger ICuV (17.79 mL [IQR 1.57-42.75] vs 6 mL [-0.31 to 12.51], p = 0.003) compared to normoglycemic patients. No significant ICuV differences between patients with and without anemia were seen. Multivariable regression analysis revealed an association between perfusion scotoma and hyperglycemia, adjusted odds ratio (OR) 2.48 (95% CI 1.25-4.92), and between perfusion scotoma and blood glucose levels, adjusted OR 1.19 (95% CI 1.03-1.39) per 1 mmol/L increase. In our study, CTP-based ischemic core underestimation was common and associated with higher baseline blood glucose levels. Individual metabolic factors beyond perfusion that critically influence the infarct growth rate should be considered when interpreting baseline CTP estimations of ischemic core.

Author Response: Statin Therapy for Secondary Prevention in Ischemic Stroke Patients With Cerebral Microbleeds

Author Response: Statin Therapy for Secondary Prevention in Ischemic Stroke Patients With Cerebral Microbleeds

Prevalence and Clinical Implications of Hemosiderin Deposits in Recent Small Subcortical Infarcts.

A quarter of ischemic strokes are of lacunar clinical subtype and have an underlying recent small subcortical infarct (RSSI), but their long-term outcomes remain poorly characterized. Hemosiderin deposits (HDs) have been noted in RSSIs at chronic stages and might mimic primary hemorrhage. We characterized HDs' morphology, frequency, and clinical relevance. Participants with RSSIs were identified from a prospective longitudinal study and evaluated on 3T MRI including susceptibility-weighted imaging (SWI) from stroke diagnosis to 12 months. We categorized HDs in RSSIs on SWI at all available time points into 4 types (spots, smudge, rim, cluster) and assessed their associations with demographic factors, stroke-related factors, and image markers with adjusted logistic regression. HDs were observed in 43 (55.0%) of 108 participants within 3 months and 83 (76.9%) of 108 within 12 months after stroke onset. The mean time to first detection of HDs was 87 (interquartile range 53-164) days. A "rim" pattern (similar to late appearance of primary hemorrhage) occurred in at least 26.5% of RSSIs at all follow-up time points, mainly those located in the lentiform/internal capsule (50.0%) or thalamus (36.4%). Infarct volume (odds ratio [OR] 1.003, 95% CI 1.001-1.006; p = 0.004) and the total small vessel disease (SVD) score at baseline (OR 2.50, 95% CI 1.28-4.86, p = 0.007) independently predicted HDs at 12 months. HDs were positively associated with more lacunes (OR 1.60, 95% CI 1.13-2.26, p < 0.01), but not the Fazekas score, number of microbleeds, basal ganglia mineral deposit score, or clinical outcomes. HDs occur commonly in RSSIs and may be associated with infarct volume and SVD score. Hemosiderin "rim" is common in RSSIs, urging caution to avoid mistaking ischemic RSSI for primary hemorrhage in subacute and chronic stages.

Electroacupuncture Serum Protects Blood-brain Barrier Damage after Ischemic Stroke BY Regulating the Pericytes in vitro.

Electroacupuncture (EA) exerts a protective role in Blood-Brain Barrier (BBB) damage after ischemic stroke, but whether this effect involves the regulation of the pericytes in vitro is unclear. The in vitro BBB models were established with brain microvascular endothelial cells (BMECs) and pericytes, and the co-cultured cells were randomly divided into three groups: the control group, oxygen-glucose deprivation/reoxygenation (OGD/R) group and EA group. OGD/R was performed to simulate cerebral ischemia-reperfusion in vitro. EA serum was prepared by EA treatment at the "Renzhong" (GV26) and "Baihui" (GV20) acupoints in middle cerebral artery occlusion/ reperfusion rats. Furthermore, the characteristics of BMECs and pericytes were identified with immunohistochemistry staining. The cell morphology of the BBB model was observed using an inverted microscope. The function of BBB was measured with transendothelial electrical resistance (TEER) and sodium fluorescein, and the viability, apoptosis, and migration of pericytes were detected by cell counting kit-8, flow cytometry, and Transwell migration assay. BMECs were positive staining for Factor-VIII, and pericytes were positive staining for the α-SMA and NG2. EA serum improved cell morphology of the BBB model increased TEER, and decreased sodium fluorescein in OGD/R condition. Besides, EA serum alleviated pericytes" apoptosis rate and migration number, and enhanced pericytes' viability rate in OGD/R condition. EA serum protects against BBB damage induced by OGD/R in vitro, and this protection might be achieved by attenuating pericytes apoptosis and migration, as well as enhancing pericytes viability. The findings provided new evidence for EA as a medical therapy for ischemic stroke.

Pretreatment Cranial Computed Tomography Perfusion Predicts Dynamic Cerebral Autoregulation Changes in Acute Hemispheric Stroke Patients Having Undergone Recanalizing Therapy: A Retrospective Study

Objectives: Blood pressure (BP) management is challenging in patients with acute ischemic supratentorial stroke undergoing recanalization therapy due to the lack of established guidelines. Assessing dynamic cerebral autoregulation (dCA) may address this need, as it is a bedside technique that evaluates the transfer function phase in the very low-frequency (VLF) range (0.02–0.07 Hz) between BP and cerebral blood flow velocity (CBFV) in the middle cerebral artery. This phase is a prognostically relevant parameter, with lower values associated with poorer outcomes. This study aimed to evaluate whether early cranial computed tomography perfusion (CTP) can predict this parameter. Methods: In this retrospective study, 165 consecutive patients with hemispheric strokes who underwent recanalizing therapy were included (median age: 73 years; interquartile range (IQR) 60–80; women: 43 (26%)). The cohort comprised 91 patients treated with intravenous thrombolysis (IV-lysis) alone (median National Institute of Health Stroke Scale (NIHSS) score: 5; IQR 3–7) and 74 patients treated with mechanical thrombectomy (median NIHSS: 15; IQR 9–18). Regression analysis was performed to assess the relationship between pretreatment CTP-derived ischemic penumbra and core stroke volumes and the dCA VLF phase, as well as CBFV assessed within the first 72 h post-stroke event. Results: Pretreatment penumbra volume was a significant predictor of the VLF phase (adjusted r2 = 0.040; β = −0.001, 95% confidence interval (CI): −0.0018 to −0.0002, p = 0.02). Core infarct volume was a stronger predictor of CBFV (adjusted r2 = 0.082; β = 0.205, 95% CI: 0.0968–0.3198; p = 0.0003) compared to penumbra volume (p = 0.01). Additionally, in the low-frequency range (0.07–0.20 Hz), CBFV and BP were inversely related to the gain, an index of vascular tone. Conclusion: CTP metrics appear to correlate with the outcome-relevant VLF phase and reactive hyperemic CBFV, which interact with BP to influence vascular tone and gain. These aspects of dCA could potentially guide BP management in patients with acute stroke undergoing recanalization therapy. However, further validation is required.

Study on the Mechanism of miR-124-3p Regulating Cerebral Ischemia-Reperfusion Injury

Objective: To investigate the role of miR-124-3p in ischemia-reperfusion injury following ischemic stroke and to evaluate the neuroprotective effects of miR-124-3p inhibition on neurological outcomes, infarct size, and apoptosis. Methods: A middle cerebral artery occlusion (MCAO) model was used to induce ischemia-reperfusion injury in rats. Experimental groups included a sham surgery group, an MCAO group, an MCAO + miR-124-3p NC group, and an MCAO + miR-124-3p antagomir group. Neurological deficits were assessed at 2, 8, and 24 hours post-ischemia. Infarct size and apoptosis levels were measured using brain tissue weight analysis and TUNEL assay, respectively, to evaluate the extent of ischemic damage and cell death. Results: The MCAO group showed progressively worsening neurological deficits, increased infarct size, and extensive apoptosis. In contrast, miR-124-3p inhibition significantly reduced neurological deficits, with lower scores at all time points. The MCAO + miR-124-3p inhibitor group demonstrated a significant reduction in infarct size compared to the MCAO group and the NC group, suggesting tissue preservation. Additionally, the miR-124-3p inhibitor group showed markedly reduced apoptosis, as evidenced by decreased TUNEL-positive signals, indicating a reduction in cell death following ischemia-reperfusion injury. Conclusion: Inhibition of miR-124-3p plays a neuroprotective role in ischemia-reperfusion injury by mitigating neurological deficits, reducing infarct size, and lowering apoptosis levels. These findings suggest that miR-124-3p inhibition could be a promising therapeutic target for minimizing brain damage and improving recovery in ischemic stroke patients.

Sick leave and homecare need in patients with transient ischaemic attack compared with ischaemic stroke: A nationwide follow-up study.

Emerging evidence indicates lasting impairments in patients with transient ischaemic attack (TIA), which may be unexpected as symptoms per definition recover within 24 h. How these impairments impact return to work or the ability to maintain independence is unknown. The aim of our study was to investigate the need of sick leave or homecare following TIA compared with acute ischaemic stroke (AIS). Patients registered with TIA in the Danish Stroke Registry from 2014 to 2021 were included. Information on sick leave benefits and use of homecare was obtained from national registries. The cumulative risk of sick leave or homecare was calculated and compared with AIS. A hazard rate ratio (HRR) for return to work was calculated. In total, 29,261 TIA and 64,295 AIS events were included. For TIA, 6770 patients paid labour market contribution before TIA, of which 1240 patients (18.3%) received sick leave benefits after 5-12 weeks. For AIS 48.1% (5940 of 12,340) received sick leave benefits. The HRR for return to work was 2.37 (95% confidence interval 2.13-2.64). For patients aged 65-79, a total of 15.4% TIA (175 of 1136) and 30.6% AIS (1443 of 4716) started to receive homecare at 3 months. The HRR was 0.55 (95% confidence interval 0.49-0.62). Despite the transient event almost one out of five working patients with TIA receive sick leave benefits 5-12 weeks after. Initiation of homecare was required in nearly one out of six patients with TIA aged 65-79 years.

Comparative Evaluation of Variations in Cerebral Arterial Circulation on Imaging in Stroke and Non-Stroke Patients

Comparative Evaluation of Variations in Cerebral Arterial Circulation on Imaging in Stroke and Non-Stroke Patients

Transcriptomic Profiling Reveals Sex-Specific Epigenetic Dynamics Involving kdm6b and H3K27 Methylation in Cerebral Ischemia-Induced Neurogenesis and Recovery.

Cerebral ischemic stroke ranks among the leading causes of death and disability worldwide. A significant challenge, beyond the lack of effective therapies, is the frequent oversight of sex as a vital factor in stroke research. This study focuses on elucidating the sex-specific epigenetic mechanisms that contribute to neural damage and recovery in cerebral ischemia. In our previously reported study, we demonstrated that following ischemia-induced cerebral artery occlusion (ICAO), female striatal tissue exhibited an early reinstatement of H3K9me2 marks on the promoters of inflammatory genes compared to male striatal tissue. This restoration led to a reduction in the expression of inflammatory cytokines, ultimately contributing to accelerated recovery in females. Building upon these findings, the current study aimed to investigate the unidentified molecular pathways responsible for the accelerated recovery observed in females. To explore this, we performed illumina-RNA sequencing on striatal tissues 24-h post-ICAO. Interestingly, our analysis revealed differential regulation of H3K27me2 marks on the promoters of various neurogenic genes at an early stage, which facilitated early neurogenesis in the female striatum. This investigation identifies an epigenetic modulator, kdm6b/jmjd3, targeting H3K27, and delineates its sex-specific role in neural stem cell proliferation. The findings contribute to a comprehensive model linking gender-specific epigenetic regulation, neurogenesis, and post-ICAO recovery. In conclusion, the identified epigenetic modulators and their roles in neurogenesis offer potential targets for refined therapeutic interventions, emphasizing the importance of personalized and sex-specific considerations in stroke studies.

The clinical value of fibrosis indices for predicting the hemorrhagic transformation in patients with acute ischemic stroke after intravenous thrombolysis

BackgroundThe incidence of stroke in China is approximately 343 per 100,000 people each year, the highest rate worldwide. Hemorrhagic transformation (HT), particularly symptomatic intracerebral hemorrhage (sICH) following acute ischemic stroke (AIS) with or without intravenous thrombolysis (IVT), can lead to rapid neurological deterioration, poor prognosis, and even death. Non-alcoholic fatty liver disease (NAFLD) has been identified as a risk factor for stroke occurrence and associated with poor long-term functional outcomes. Nonetheless, no studies have examined the association between liver fibrosis and HT in AIS patients who underwent IVT.MethodA total of 826 patients with AIS who underwent IVT were included in this study. We calculated nine validated liver fibrosis indices to assess the extent of liver fibrosis. HT was detected by follow-up cranial CT/MRI within 24 h post-IVT and was classified as either hemorrhagic infarction (HI) or parenchymal hematoma (PH). Symptomatic intracranial hemorrhage was defined as a sudden symptomatic neurological deterioration, indicated by an increase in (National Institutes of Health Stroke Scale) NIHSS score of 4 points or more.ResultThe median values of fibrosis-4 (FIB-4), modified FIB-4 (mFIB-4), aspartate aminotransferase (AST)-platelet ratio index (APRI), Forns index, alanine aminotransferase (ALT)/AST (ARR), AST/ALT ratio-platelet ratio index (AARPRI), fibrosis quotient (FibroQ), and Fibrosis Index were significantly higher, while the fibrosis-5 (FIB-5) was significantly lower in the HT and sICH groups (all P &amp;lt; 0.001). After adjusting for potential confounders, all nine liver fibrosis indices remained associated with HT and sICH. Receiver operating characteristic (ROC) curve analysis revealed that the FibroQ score had the best predictive ability for HT (AUC = 0.707, CI = 0.652–0.762, P &amp;lt; 0.001), while FIB-4 had the best predictive ability for sICH (AUC = 0.802, CI = 0.711–0.892, P &amp;lt; 0.001).ConclusionLiver fibrosis, as validated by FIB-4, mFIB-4, FIB-5, APRI, Forns index, ARR, AARPRI, FibroQ, and Fibrosis Index, was associated with HT and sICH in AIS patients after IVT.

Transformer Dil-DenseUnet: An Advanced Architecture for Stroke Segmentation

We propose a novel architecture, Transformer Dil-DenseUNet, designed to address the challenges of accurately segmenting stroke lesions in MRI images. Precise segmentation is essential for diagnosing and treating stroke patients, as it provides critical spatial insights into the affected brain regions and the extent of damage. Traditional manual segmentation is labor-intensive and error-prone, highlighting the need for automated solutions. Our Transformer Dil-DenseUNet combines DenseNet, dilated convolutions, and Transformer blocks, each contributing unique strengths to enhance segmentation accuracy. The DenseNet component captures fine-grained details and global features by leveraging dense connections, improving both precision and feature reuse. The dilated convolutional blocks, placed before each DenseNet module, expand the receptive field, capturing broader contextual information essential for accurate segmentation. Additionally, the Transformer blocks within our architecture address CNN limitations in capturing long-range dependencies by modeling complex spatial relationships through multi-head self-attention mechanisms. We assess our model’s performance on the Ischemic Stroke Lesion Segmentation Challenge 2015 (SISS 2015) and ISLES 2022 datasets. In the testing phase, the model achieves a Dice coefficient of 0.80 ± 0.30 on SISS 2015 and 0.81 ± 0.33 on ISLES 2022, surpassing the current state-of-the-art results on these datasets.

Effects of electroacupuncture on expression of miR-218 and HMGB1/TLR4 signaling pathway in rats with focal cerebral ischemia

To observe the effect of electroacupuncture (EA) on high mobility group box 1 (HMGB1) / toll-like receptor 4 (TLR4) signaling pathway and inflammatory injury in rats with focal cerebral ischemia (FCI), so as to explore its mechanisms underlying amelioration of ischemic stroke. Male SD rats were randomly divided into sham operation (n=18), model (n=18) and EA (n=18) groups. The FCI model was established according to Longa's method. In the EA group, 24 h after modeling, EA stimulation was applied to "Baihui"(GV20), "Fengfu"(GV16), and "Neiguan" (PC6) and "Xinshu" (BL15) on the left side for 20 min, once a day for 1 week. The neurological deficit severity was evaluated by the modified neurological severity score (mNSS), and the morphological changes of neurons were observed after H.E. staining. The expression of HMGB1 and TLR4 proteins were detected by immunofluorescence staining. The contents of tumor necrosis factor(TNF)-α and interleukin(IL)-6 in the ischemic area tissue of the brain were detected using ELISA. The mRNA expressions of HMGB1 and TLR4 as well as the expression of miR-218 in the ischemic cortex were detected by PCR. Compared with the sham operation group, the mNSS at 2 h, 48 h and 7 day (d), IL-6 and TNF-α contents, HMGB1 and TLR4 immunoactivity and mRNA expression at 48 h and 7 d were significantly increased (P<0.01), while miR-218 expression at 48 h and 7 d was obviously down-regulated (P<0.01) in the model group. In comparison with the model group, the mNSS at 7 d, IL-6 and TNF-α contents, HMGB1 and TLR4 immunoactivity and mRNA expression at 7 d not at 48 h were significantly decreased (P<0.01, P<0.05), while the expression of miR-218 at 7 d was apparently up-regulated (P<0.05) in the EA group. H.E. staining showed that there were signs of neuronal necrosis including blurred outline of the cells, disordered internal structure, dense cytoplasm, shrunk nuclei, etc. in the ischemic area of the brain at 48 h and 7 d in the model group, which was evidently milder on day 7 in the EA group. EA can reduce the inflammatory injury of brain tissue and improve the neurological impairment in rats with FCI, which may be associated with its effects in inhibiting HMGB1/TLR4 signaling and down-regulating the level of pro-inflammatory cytokines.

Effect of He's qiangtong method of acupuncture on serological levels in patients with acute ischaemic stroke

To investigate the repair effects of He's qiangtong method of acupuncture (involved bloodletting technique with strong action of unblocking) on the neurovascular unit of the patients with acute ischemic stroke (AIS) in terms of serological indicators so as to provide new ideas for the treatment of AIS. Seventy subjects with AIS were randomly divided into an observation group (35 cases, 1 case dropped out) and a control group (35 cases , 4 cases dropped out). Patients in the control group were treated with conventional regimen. In the observation group, the bloodletting was operated, combined with the conventional treatment. Bloodletting was performed at Baihui (GV20), Sishencong (EX-HN1) and bilateral Erjian (EX-HN6), using He's qiangtong method of acupuncture, 3 times a week and for 2 weeks. Before and after treatment, the scores of the national institute of health stroke scale (NIHSS), the modified Rankin scale (MRS), and the Barthel index were evaluated；and the serological levels of the serum brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE) and blood-brain barrier permeability-associated protein (S100β protein) were detected in the two groups. After treatment, NIHSS score and MRS score were decreased (P<0.01), and Barthel score was increased (P<0.01) in both groups. NIHSS score of the observation group was lower than that of the control group (P<0.01). Compared with those before treatment, the content of BDNF in both groups increased (P<0.05), and VEGF content was elevated in the observation group (P<0.05) after treatment. The total effective rate was 100% (34/34) in the observation group, higher than that (67.74%, 21/31) in the control group (P<0.01). He's qiangtong method of acupuncture can promote the recovery of neurological deficits in AIS patients and effectively improve their motor function and the activity of daily living, which may be related to the reconstruction of neurovascular unit in the brain of AIS patients by increasing the levels of serological repair factors.