Cerebral Infarction Research Articles

0.23-Tesla MRI to differentiate between ischaemic and haemorrhagic strokes within 24 hours of onset: a combined experimental–clinical study

Background and purposeThe low-field MRI is a promising tool to accurately diagnose strokes. We here report our study on the accuracy of a 0.23-Tesla (0.23-T) MRI using the haematoma enhanced...

Serum TNF alpha concentration and arterial age of patients with acute cerebral infarction

Serum TNF alpha concentration and arterial age of patients with acute cerebral infarction

Effect of voxelotor on cerebral perfusion and cerebral oxygen metabolism and cardiac stress in adult patients with sickle cell disease.

Sickle cell disease (SCD) is complicated by silent cerebral infarcts (SCIs), for which anemia is an important risk factor. Despite normal oxygen delivery (OD), cerebral vascular reserve (CVR), and cerebral metabolic rate of oxygen (CMRO2) are diminished in SCD, possibly causing the formation of SCIs. Voxelotor inhibits polymerization by increasing the hemoglobin oxygen binding, ameliorating hemolytic anemia. Furthermore, anemia is related to cardiac complications. Our aims were to assess the effect of voxelotor on markers of cerebral perfusion, cerebral oxygen metabolism, and markers of cardiac stress in SCD patients. Cerebral hemodynamics and oxygen metabolism were measured with MRI before and after 3 months of voxelotor treatment (1500 mg/day) in 18 adults with SCD (HbSS/HbSβ0-thalassemia). Hemoglobin levels significantly increased (p = .001) and markers of hemolysis decreased (p < .05). OD increased from 6.5 (IQR, 6.0-7.1) mL O2/100 g/min to 8.1 (IQR, 7.2-8.7) mL O2/100 g/min (p = .001). CBF and CVR did not change. CMRO2 decreased from 2.0 (IQR, 1.9-2.1) mL O2/100 g/min to 1.9 (IQR, 1.6-2.1) mL O2/100 g/min (p = .03). N-terminal pro-B type natriuretic peptide (NT-proBNP) levels decreased (p = .048) and maximum tricuspid regurgitation flow velocity (TRVmax) normalized in all but one patient with increased TRVmax. Voxelotor treatment in patients with severe SCD did not decrease CBF despite increased Hb levels. Cerebral oxygen metabolism slightly decreased, despite raised OD, most likely due to drug-induced increase in oxygen binding. Nonetheless, voxelotor improved clinically validated markers of cardiac stress.

Protective Role of Vitamin D Receptor in Cerebral Ischemia/Reperfusion Injury In Vitro and In Vivo Model.

Vitamin D receptor (VDR) can prevent myocardial ischemia reperfusion injury (MIRI). Hence, we aimed to illuminate the effect of VDR on cerebral ischemia/reperfusion injury (CIRI). C57BL/6 mice and SK-N-SH cells were utilized to establish CIRI and cellular oxygen deprivation/reoxygenation (OGD/R) models. Mice were injected with 1 μg/kg Calcitriol or 1 μg/kg Paricalcitol (PC) and adenovirus-mediated VDR overexpression or knockdown plasmids. 2,3,5-triphenyl-tetrazolium chloride (TTC) and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were performed to measure the brain infarct volume and the apoptosis of cerebral cells. SK-N-SH cells were treated with 5 mM N-acetyl-L-cysteine (NAC) and transfected with VDR knockdown plasmid. Flow cytometry and Cell Counting Kit-8 (CCK-8) assays were employed to assess the apoptosis and cell viability. Enzyme-Linked Immunosorbent Assay (ELISA), quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) and Western blot were exploited to quantify the levels of reactive species oxygen (ROS), other oxidative stress-related factors, VDR and apoptosis-related factors. The level of VDR in mouse cerebral tissue was elevated by CIRI (p < 0.001). CIRI-induced cerebral infarction (p < 0.001) and the apoptosis of cerebral cells (p < 0.001) in mice were mitigated by the activation of VDR. VDR overexpression abrogated while VDR silencing enhanced CIRI-induced infarction, oxidative stress and apoptosis of cerebral cells (p < 0.05). Furthermore, VDR silencing aggravated the oxidative stress and apoptosis in OGD/R-treated SK-N-SH cells (p < 0.05). NAC, a scavenger of oxidative stress, could reverse the effects of VDR silencing on apoptosis and oxidative stress in OGD/R-treated SK-N-SH cells (p < 0.01). VDR alleviates the oxidative stress to protect against CIRI.

Functional Outcomes and Complications of Carotid Tandem Lesions After Mechanical Thrombectomy for Treatment of Large-Vessel Occlusion Stroke.

Large Vessel Occlusion (LVO) stroke patients with tandem lesions (TLs) have been observed to have worse outcomes when compared to patients with simple isolated intracranial occlusions. To examine the difference in post-operative functional status at discharge for patients treated with mechanical thrombectomy for an acute LVO stroke based on the presence of a tandem carotid lesion. This is a retrospective cohort study of 589 patients presenting within the first 24hours of stroke onset who underwent mechanical thrombectomy. The primary outcome was functional status quantified by modified Rankin Score (mRS) at time of discharge. The secondary outcomes were presence of hemorrhagic conversion, midline shift >5cm, malignant cerebral edema, reocclusion, Thrombolysis in Cerebral Infarction Scale (TICI), and discharge location. Patients with tandem occlusions and those with isolated intracranial lesions had similar baseline demographics. However, in patients with TLs, there was a significantly higher NIH stroke scale at admission and a longer time to recanalization. Modified Rankin Score prior to admission was similar for both groups, but was significantly higher in patients with TLs at discharge. The secondary outcomes were similar for hemorrhagic conversion, discharge to hospice, and a TICI scale of 0, but were significantly worse for patients with TLs for in-hospital mortality, midline shift >5mm, and malignant cerebral edema. The presence of a tandem lesion predicted a higher modified Rankin Score at discharge in univariate regression modeling (β = .45; P-value = .006). The two groups were similar in baseline characteristics and cardiovascular risk factors, yet patients with tandem carotid lesions experienced more complications during their hospitalization and had greater functional disability at discharge. Patients with a TL had a longer mean time to recanalization, representing a potential explanation for these differences in outcomes.

Long term outcomes of intracarotid arterial transfusion of circulatory-derived autologous CD34 + cells for acute ischemic stroke patients—A randomized, open-label, controlled phase II clinical trial

BackgroundThis phase II randomized controlled trial tested whether the intracarotid arterial administration (ICAA) of autologous CD34 + cells to patients within 14 ± 7 days after acute ischemic stroke (IS) could be safe and further improve short- and long-term outcomes.MethodsBetween January 2018 and March 2022, 28 consecutive patients were equally randomly allocated to the cell-treated group (CD34 + cells/3.0 × 107/patient) or the control group (receiving optimal medical therapy). CD34 + cells were transfused into the ipsilateral brain infarct zone of cell-treated patients via the ICAA in the catheterization room.ResultsThe results demonstrated 100% safety and success rates for the procedure, and no long-term tumorigenesis was observed in cell-treated patients. In cell-treated patients, the angiogenesis capacity of circulating endothelial progenitor cells (EPCs)/Matrigel was significantly greater after treatment than before treatment with granulocyte colony-stimulating factor (all p < 0.001). Blood samples from the right internal jugular vein of the cell-treated patients presented significantly greater levels of the stromal cell-derived factor 1α/EPC at 5, 10 and 30 min compared with 0 min (all p < 0.005). The National Institute of Health Stroke Scale scores were similar upon presentation, but a greater response was observed by Days 30 and 90 in the cell-treated group than in the control group. Tc-99 m brain perfusion was significantly greater at 180 days in the cell-treated group than in the control group (p = 0.046). The combined long-term end points (defined as death/recurrent stroke/or severe disability) were notably lower in the control group compared with the cell-treated group (14.3% vs. 50.0%, p = 0.103).ConclusionIntracarotid transfusion of autologous CD34 + cells is safe and might improve long-term outcomes in patients with acute IS.Trial registration ISRCTN, ISRCTN15677760. Registered 23 April 2018- Retrospectively registered, https://doi.org/10.1186/ISRCTN15677760

Safety and Efficacy of Thrombectomy in Vietnamese Stroke Patients Selected Through Perfusion Imaging With an Onset Time Between 6-24 Hours.

Introduction Recent trials have demonstrated the remarkable benefit of endovascular treatment (EVT) up to 24 hour in patients with large vessel occlusion (LVO) and target mismatch profiles; however, benefits of late-window EVT in Vietnamese population remain poorly understood. This study aims to evaluate the real-world outcomes of EVT in acute ischemic stroke (AIS) patients selected using perfusion imaging within the 6- to 24-hour window. Methods A prospective study of consecutive patients with anterior circulation LVO stroke who underwent EVT within 6 to 24 hours after last known well between August 2022 and March 2024. Patients were selected based on the DAWN/DEFUSE-3 criteria (Perfusion-RAPID, iSchemaView). The primary outcome was the proportion of patients with functional independence at 90 days (modified Rankin Scale score of 0-2). The secondary outcomes were successful reperfusion defined by thrombolysis in cerebral infarction (TICI) ≥2b on the final procedure, and subgroup analysis between good (Hypoperfusion intensity ratio (HIR) <0.4) and poor collaterals (HIR ≥ 0.4) groups. Safety outcomes were mortality rate and symptomatic intracranial hemorrhage (sICH). Results Of 122 enrolled patients, 68% met inclusion criteria of DEFUSE-3 trial, 61% met DAWN trial criteria. Mean age was 66 years, median baseline NIHSS was 13, median time from stroke onset to hospital arrival was 12.55 hours (9.50 - 16.48), and median infarct volume was 11.5 mL. The rate of functional independence at 90 days was 45.9%. Successful reperfusion (TICI score of ≥2b) was achieved by 83.6% of cases. The 90-day mortality rate was 10.7%, sICH was reported in 8 patients (6.6%). Patients with good collaterals had better functional outcome. Conclusions This real-world observational study suggests that late window EVT may be safe and effective in eligible Vietnamese patients selected based on perfusion imaging, thus supporting its practical use in this patient population. Hypoperfusion intensity ratio is a robust indicator of collateral status and could made it a valuable addition to stroke imaging work-up in clinical setting.

EXCELLENT Registry: A Prospective, Multicenter, Global Registry of Endovascular Stroke Treatment With the EMBOTRAP Device.

The EXCELLENT registry aimed to evaluate the effectiveness of the EMBOTRAP Revascularization Device in an all-comer population in a real-world setting, with a focus on the composition of retrieved clots. EXCELLENT is a prospective, global registry of patients with acute ischemic stroke treated with EMBOTRAP as the first-line mechanical thrombectomy device conducted at 34 sites (25 sites contributing clot) from September 2018 to March 2021, utilizing core imaging and central histology laboratories blinded to clinical data, independent 90-day modified Rankin Scale assessment and Clinical Events Committee. After screening 3799 patients, a total of 997 subjects (mean age, 70.0±14.2 years; 51.8% women; 19.7% non-White) were included. The first-pass modified Treatment in Cerebral Infarction (mTICI) ≥2b rate was 64.5% (623/966), first-pass mTICI ≥2c was 39.1% (378/966), and final mTICI ≥2b was 94.5% (931/985). A total of 427/912 (46.8%) patients achieved a 90-day modified Rankin Scale of 0 to 2 or ≤baseline. Embolization to a new territory occurred in 0.2% (2/984), and symptomatic intracranial hemorrhage at 24 hours in 1.6% (16/997). The 90-day mortality was 19.1% (175/918). Device- and/or procedure-related serious adverse events occurred in 5.9% (54/912) through 90 days. The mean RBC percentage of retrieved clots was 45.62±21.372. Among patients who achieved mTICI ≥2b with the first pass, 15.7% (52/331) and 9.7% (32/331), respectively, had RBC-poor (<25%) and RBC-rich (>75%) clots. Patients with no clot retrieved in any procedural pass had a lower percentage of hyperdense or susceptibility vessel sign on baseline imaging (58.9% versus 74.7%; P<0.001), pointing to a potential preprocedure indicator of challenging clot. The EXCELLENT registry informs real-world practices in mechanical thrombectomy and sheds light on the range of clots effectively retrieved by current technology. This is the first report of detailed patient characteristics where mechanical thrombectomy maneuvers failed to remove any clot material. Although the composition of nonretrievable clots cannot be assessed histologically, the results support the notion that no retrieval may be correlated with imaging findings suggesting clots lower in RBC. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03685578.

Pharmacovigilance study of famciclovir in the Food and Drug administration adverse event reporting system database

Famciclovir, mainly used to treat herpes zoster, is rapidly transforms into penciclovir when administered orally. Our study evaluated adverse events (AEs) associated with famciclovir by mining data from the publicly available Food and Drug Administration Adverse Event Reporting System (FAERS) database, providing a reference for clinical safety. Disproportionality analysis (including reported odds ratio and proportional reporting ratio) and Bayesian methods (including Bayesian Confidence Propagation Neural Network and Gamma-Poisson Shrinkage) were used to quantify the AE signals associated with famciclovir. A total of 17,652,186 case reports were obtained from the FAERS database, and 432 famiclovir-related AEs were identified. Nausea, headache, altered mental status, vomiting, and dizziness were found to be the most common Aes, corresponding to those reported in the Food and Drug Administration (FDA) drug labelling and clinical trials. Our study found some potential AEs of famciclovir that were not mentioned in the FDA drug labelling, such as toxic encephalopathy, encephalopathy, ataxia, dysarthria, dementia, cerebral infarction, tremor, purpura, skin ulcers, acute pancreatitis, rhabdomyolysis, muscle twitching, increased blood urea, lowered blood pressure, hepatitis, disease recurrence, drug interactions, and pancytopenia. Our study identified potential famciclovir AE signals, providing insights for physicians to reduce possible side effects and promote the safe implementation of the drug in clinical settings.

Early Ischemic Stroke Assessment with ASPECTS: A Case Report Highlighting the Radiologist's Role in a Limited-Resource Setting

Background: Ischemic stroke is a leading cause of morbidity and mortality globally, particularly in resource-limited settings. Non-contrast computed tomography (NCCT) is often the primary imaging modality available in these settings, and the Alberta Stroke Program Early CT Score (ASPECTS) is a crucial tool for assessing early ischemic changes in NCCT. This case report highlights the importance of ASPECTS in guiding clinical decisions and prognostication in a resource-limited setting. Case presentation: A 79-year-old male presented to the emergency unit at Negara General Hospital, a rural facility in Bali, with acute onset of right-sided hemiparesis and speech difficulty. NCCT showed a hypodense lesion with ill-defined margins in the left insular cortex, left caudate nucleus, left internal capsule, and left frontotemporoparietal lobes, consistent with a subacute cerebral infarction in the middle cerebral artery (MCA) territory, with an ASPECTS score of 2. Due to the extensive ischemic burden and the limited availability of advanced treatment options, conservative management was chosen. The radiologist's interpretation of the ASPECTS score played a critical role in guiding the clinical team's decision-making and informing the patient's family about the prognosis. Conclusion: ASPECTS is an essential tool for predicting stroke outcomes, with lower scores correlating with larger infarct volumes and poorer prognoses. In resource-limited settings, radiologists play a vital role in interpreting ASPECTS scores to guide clinical management and provide accurate prognostic information to patients and their families.

Tanshinone IIA inhibits the apoptosis process of nerve cells by upshifting SIRT1 and FOXO3α protein and regulating anti- oxidative stress molecules and inflammatory factors in cerebral infarction model

Background As a prevalent cerebrovascular disorder, cerebral infarction (CI) has garnered extensive attention globally due to its high incidence and substantial fatality rate. Ischemia-reperfusion injury (IRI) exacerbates not only neuronal demise but also amplifies neural functional impairment. Tanshinone IIA (Tan IIA) has been identified to confer protection against IRI, yet the precise underlying mechanisms remain elusive. This work aimed to delve into the mechanistic role of Tan IIA in CI, with the goal of furnishing more distinct theoretical substantiation for its clinical application. Methods Initially, a middle cerebral artery embolization model group (MCAO) model was established, followed by the categorization of rats into distinct groups based on different administration modes. Therapeutic effects were evaluated through indices including mortality rate, cerebral tissue water content, CI proportion, and neural functional scoring. Meanwhile, cellular apoptosis rates in hippocampal and cortical tissues, as well as levels of oxidative stress molecules (OSM), Sirtuin 1 (SIRT1), Forkhead box O3 (FOXO3α), and inflammatory factors, were examined to explore the mechanism of action. Results This work revealed that within varying doses of Tan IIA groups, as dosage escalated, mortality rate, cerebral edema severity, CI proportion, and neural functional scoring gradually diminished. Notably, the 35 mg/kg dose group exhibited the most significant reductions, with decreases of 74.9%, 12.7%, 47.5%, and 54%, respectively. Cellular apoptosis rates in hippocampal and cortical tissues displayed a stepwise descending trend, with the 35 mg/kg dose group showcasing the largest reduction. SIRT1 and FOXO3α proteins exhibited a steady increase, with the 35 mg/kg dose group manifesting respective elevations of 87.9% and 65.5%, the highest among all groups. Antioxidant molecules glutathione (GSH) and superoxide dismutase (SOD) contents progressively increased, whereas malondialdehyde (MDA) and nitric oxide (NO) content decreased. The 35 mg/kg dose group recorded the highest increments of 49.1% and 58.1% for GSH and SOD content, while achieving the greatest reductions of 55.6% and 56.2% for MDA and NO content. Expression of inflammatory factors, namely tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and interleukin-6 (IL-6), gradually declined, with reductions of 42.1%, 32.2%, and 29.1%, respectively, in the 35 mg/kg dose group, exhibiting drastic differences (p < 0.05). Conclusion In conclusion, this research elucidates that Tan IIA improves cerebral edema and neural function by elevating intracellular expression of SIRT1 and FOXO3α proteins, modulating OSM and inflammatory factors. These findings yielded robust experimental support for the potential use of Tan IIA as a therapeutic agent for CI.

Cerebral vascular shunting and oxygen metabolism in sickle cell disease

AbstractPatients with sickle cell disease (SCD) are at elevated risk of silent cerebral infarcts and strokes; however, they frequently lack established stroke risk factors (eg, macrovascular arterial steno-occlusion) and, as such, the mechanisms underlying such events are incompletely characterized. This study evaluated cerebral metabolism with respect to imaging markers of vascular shunting in 143 participants with SCD, including 73 pediatric (aged 6-17 years) and 70 adult (aged 18-40 years) participants. Participants completed clinical and cerebral imaging assessments using 3-Tesla brain magnetic resonance imaging (MRI) to quantify cerebral hemometabolic measures. Vascular shunting was assessed in each patient using a previously published ordinal venous hyperintensity score (VHS) of 0, 1, or 2 on cerebral blood flow-weighted MRI. Relationships between age group (pediatric vs adults) and hemometabolic measures for varying VHS were investigated using 2-way analysis of variance. Participants with VHS of 2, indicative of the most rapid arteriovenous transit, had significantly reduced blood oxygen content (CaO2; 10.90 ± 1.69 mL O2 per 100 mL blood), oxygen extraction fraction (OEF; 33.52% ± 5.54%), and cerebral metabolic rate of oxygen consumption (CMRO2; 2.91 ± 0.69 mL O2 per 100g tissue per minute) compared with their counterparts with VHS = 0 (CaO2 = 12.42 ± 1.58 mL O2 per 100 mL blood; OEF = 39.03% ± 3.80%; CMRO2 = 3.77 ± 0.84 mL O2 per 100 g tissue per minute) or VHS = 1 (CaO2 = 11.86 ± 1.73 mL O2 per 100 mL blood; OEF = 36.37% ± 5.11%; CMRO2 = 3.59 ± 0.78 mL O2 per 100 g tissue per minute). Both pediatric and adult patients with SCD presenting with greater imaging evidence of vascular shunting had mildly reduced OEF and CMRO2. These findings highlight that imaging markers of vascular shunting are associated with significant, albeit mild, evidence of reduced OEF and CMRO2 in patients with SCD.

Outcomes of endovascular thrombectomy for acute ischaemic stroke in patients aged ≥80 years: A Hong Kong stroke center experience

BackgroundElderly patients contribute to the large proportion of ischaemic stroke worldwide. Currently, treatment for elderly stroke remains aggressive, as the exact age cutoff for endovascular thrombectomy (EVT) has not been well established due to a lack of large-scale randomized control trials. In this study we investigate the difference in outcome after EVT in the octogenarian and above, compared to their younger counterparts. MethodsEVT patients were divided into two groups, the octogenarian group and younger group (below age of 80). Primary outcome were the 90-days post-thrombectomy functional independence (modified Rankin scale), and Barthel index. Secondary and safety outcomes of post-thrombectomy were also analyzed, including reperfusion status (modified Thrombolysis in Cerebral Infarction (TICI) score), National Institutes of Health Stroke Scale (NIHSS), major complications and mortality rate. ResultsA total 340 patients were included from 2020 to 29 Feb 2024, and patients’ demographics were obtained. Poorer neurological outcome and functional independence were noted in octogenarian group compared with younger counterpart (OR 0.33; 95 % CI 0.14-0.51; p < 0.001). A slightly higher trend of overall post-procedural death was also identified in elder group compared with the younger group (OR 1.48; 95 % CI 0.85-2.60, p = 0.08). Subgroup analysis with more advanced age cutoff at 90 took a step further and proposed that advanced age resulting in more devastating neurological outcome. ConclusionOutcomes after endovascular thrombectomy in the elder group were significantly worse than their younger counterparts. More than 80 % of elder group who were treated with EVT required moderate functional dependence, and one in four were dead within 90-days post-EVT.

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.

Research progress on the role of -glucan in obesity suppression through the gut microbiota

Abstract. Globally, the prevalence of chronic illnesses is on an upward trajectory. With the number of patients suffering from hypertension, cardiovascular diseases, or obesity rising globally. worlds population will be severely affected in their daily lives and work. Metabolic dysregulation caused by obesity can likely lead to a series of metabolic diseases such as hypertension, hyperlipidemia, and diabetes, while also increasing the risk of neurological disorders such as cerebral infarction or hemorrhage. numerous studies have shown that regulating the gut microbiota through the consumption of -glucan can effectively address obesity from multiple perspectives. Therefore, researching the mechanism by which -glucan affects chronic diseases through its action on the gut microbiota holds significant implications for the prevention and treatment of chronic diseases.

Hemorrhagic stroke code the transition to comprehensive stroke code

As recommended by the working group of vascular and interventional neurology of the Colombian Association of Neurology (ACN), stroke is defined as a neurological emergency characterized by a sudden neurological deficit potentially of arterial origin. Upon confirmation via neuroimaging, the diagnosis is rendered as cerebral infarction (CI) or hemorrhage, either intracerebral (ICH) or subarachnoid (SAH). Additionally, it can be of venous origin, such as cerebral venous thrombosis (CVT). The stroke code is currently widely recognized as a time-is-brain strategy that seeks to meet strict time goals for treating ischemic stroke (iS), which have substantially improved the outcomes of stroke patients. However, this has not been the case for hemorrhagic stroke (hS), which, given the conditions, is also admitted through the emergency department and clearly benefits from having a standardized protocol of care and time goals, like iS, to improve patient outcomes. The strategy recommended by the ACN for the early identification of a stroke is CORRE+. This acronym was created by neurologist Luis Roa and is designed to facilitate the identification of both ischemic and hemorrhagic strokes of anterior or posterior circulation. It comprises the following criteria: C: twisted face and/or worst headache, O: eye sudden alteration of vision, R: rapid weakness of an arm and/or leg, R: rare when speaking, E: altered balance + emergencies attend. The acronym is intended to be used by the general community and in different extra- and intra-hospital scenarios for immediate consultation.

Extracellular vesicles derived from endothelial progenitor cells modified by Houshiheisan promote angiogenesis and attenuate cerebral ischemic injury via miR-126/PIK3R2

Angiogenesis following cerebral ischemia is crucial for restoring blood supply to the ischemic region. Extracellular vesicles (EVs) derived from endothelial progenitor cells (EPCs) offer potential therapeutic benefits in the treatment of cerebral ischemia. Houshiheisan (HSHS) has been shown to improve clinical outcomes in ischemic stroke patients, reduce cerebral ischemic damage in rats, and protect endothelial cells. However, the potential effects of HSHS-modified EPC-derived EVs (EVsHSHS) for cerebral ischemia remain unexplored. This study investigated the impact of EVsHSHS on angiogenesis using rats with permanent middle cerebral artery occlusion (pMCAO) and brain microvascular endothelial cells (BMECs) subjected to oxygen-glucose deprivation (OGD). Results demonstrated that EVsHSHS promoted the proliferation, migration, and tube formation of BMECs in vitro. In vivo, high doses of EVsHSHS exhibited better performance than equivalent doses of unmodified EPC-derived EVs in reducing cerebral infarction volume, improving cortical blood perfusion, decreasing neurological deficit scores, and increasing cortical microvessel density at day 7 post-modeling. The pro-angiogenic effects of EVsHSHS following cerebral ischemia were associated with the regulation of miR-126 and the PIK3R2/PI3K/AKT pathway.

Cerebral Infarct Growth: Pathophysiology, Pragmatic Assessment, and Clinical Implications.

Cerebral ischemic injury occurs when blood flow drops below a critical level, resulting in an energy failure. The progressive transformation of hypoperfused viable tissue, the ischemic penumbra, into infarction is a mechanism shared by patients with ischemic stroke if timely reperfusion is not achieved. Yet, the pace at which this transformation occurs, known as the infarct growth rate (IGR), exhibits remarkable heterogeneity among patients, brain regions, and over time, reflecting differences in compensatory collateral flow and ischemic tolerance. We review (1) the pathophysiology of infarct growth, (2) the advantages and pitfalls of different approaches of IGR measurement, (3) research gaps for future studies, and (4) the clinical implications of stroke progressor phenotypes. The estimated average IGR in patients with acute large vessel occlusion stroke is 5.4 mL/h although there is wide variability based on ischemic stroke subtype, occlusion location, presence of collaterals, and patient baseline status. The IGR can be calculated using various pragmatic strategies, mostly either quantifying the extension of the infarct at a particular time and dividing this measure by the time that elapsed from symptom onset to imaging assessment or by using collateral blood flow status as a radiological surrogate marker. The IGR defines a spectrum of clinical stroke phenotypes, often dichotomized into fast and slow progressors. An IGR ≥10 mL/h and the perfusion metric hypoperfusion intensity ratio ≥0.5 are commonly used definitions of fast progressors. A nuanced understanding of the IGR and stroke progressor phenotypes could have clinical implications, including informing prognostication, acute decision-making in peripheral-to-comprehensive transfer patients eligible for thrombectomy, and selection for adjuvant neuroprotective agents.

Higher burden of cerebral small vessel disease is associated with risk of incident stroke in community dwelling individuals.

Mild manifestations of individual cerebral small vessel disease (CSVD) markers are common and may not denote increased risk, but high CSVD burden identifies individuals at increased risk of stroke and dementia. Scores incorporating multiple individual CSVD markers may better identify a person's risk. We related a multi-marker CSVD score to risk of incident stroke and compared it with the Framingham Stroke Risk Profile (FSRP) in community-dwelling individuals. Framingham Heart Study participants aged ≥55 years, free of stroke and dementia and with brain magnetic resonance imaging ratings of CSVD markers were included. A multi-marker CSVD score reflecting increasing CSVD burden was used, assigning one point each for presence of cerebral microbleeds, severe perivascular spaces, extensive white matter hyperintensities, covert brain infarcts, and cortical superficial siderosis. Multivariable Cox proportional hazards regression analyses were used to relate CSVD score to incident stroke. Among 1,154 participants (46% male, mean age 70.9±8.7), 92 (8%) developed stroke over a median follow-up of 8.6 years (Q1-Q3: 5.1-12.5). In models adjusting for age, sex, time interval between clinic exam and MRI, FHS cohort, and FSRP, those with three or more markers had increased risk of stroke (HR: 2.62; 95% CI: 1.17-5.88). In comparison, a 5-percent increase in FSRP was also associated with increased risk (aHR: 1.16; 95% CI: 1.04-1.29). The FSRP and CSVD score had similar model discrimination metrics. Higher CSVD burden is associated with increased risk of stroke, beyond the effect explained by risk factors in the FSRP. These findings support consideration of CSVD burden to identify risk of stroke in community-dwelling individuals for early implementation of preventive strategies.

Diosmin alleviates NLRP3 inflammasome-dependent cellular pyroptosis after stroke through RSK2/CREB pathway

In the context of our previous analyses on the main active ingredients of Jieyudan, a classic formula targeting aphasia in stroke, we further delve into the function and mechanisms of its active ingredient, Diosmin (DM), which may exert neuroprotective effects, in ischemic stroke. Herein, bioinformatics analysis revealed targets of DM and their intersection with differentially expressed genes in ischemic stroke. Middle cerebral artery occlusion (MCAO) rats and oxygen-glucose deprivation (OGD) cells were used to construct in vivo and in vitro models of ischemic stroke. The effects of DM on MCAO rats were assessed by Zea-Longa score, Morris water maze, TTC staining, Nissl staining, immunohistochemistry, and Western blot. At the cellular level, cell counting kit-8 assay and Western blot were carried out to verify the mechanism of DM in ischemic stroke. In vivo, DM decreased neurological deficit score, cerebral infarct volume and neuronal damage, and improved cognitive function in MCAO rats. In vitro, DM increased the viability of OGD-treated cells. In addition, DM down-regulated the expressions of NLR family pyrin domain containing 3 (NLRP3) and pyroptosis-associated proteins, while up-regulating ribosomal protein S6 kinase A3 (RSK2) level and activating cyclic-AMP response element-binding protein (CREB) signaling. Conversely, RSK2 inhibitor LJH685 reduced the viability and promoted pyroptosis-associated protein levels, which also partially reversed the effects of DM in vitro. Collectively, DM plays a therapeutic role in ischemic stroke by inhibiting NLRP3 inflammasome-mediated cellular pyroptosis via the RSK2/CREB pathway.