Cerebral Infarction Research Articles

Atrial fibrillation and risk of cognitive impairment and dementia: Relationships, potential mechanisms, and current therapies

Atrial fibrillation (AF), cognitive impairment, and dementia are significant health concerns. The prevalence and incidence of AF have been increasing and are expected to increase continuously in the future. In recent years, emerging evidence has indicated that AF, cognitive dysfunction, and dementia are associated with one another. Given the global increase in individuals who are at risk for AF, a greater focus is needed on the primary and secondary prevention of cognitive impairment and dementia in high-risk groups. Although earlier studies hypothesized that ischemic stroke is the main cause of cognitive impairment and dementia in patients with AF, recent studies have demonstrated that AF may contribute to cognitive impairment in the absence of stroke through other mechanisms. To date, various pathomechanisms have been proposed to explain the association between AF and cognitive decline, including overt ischemic stroke, silent cerebral infarctions, impaired cerebrovascular reactivity, decreased cerebral blood perfusion, neuroinflammation, microbleeds, and shared risk factors. However, a complete understanding of these mechanisms remains elusive. In addition, whether treatments targeting AF, including anticoagulation and rhythm control strategies, can avert cognitive decline and dementia has great clinical implications. To pave the way for targeted effective interventions for cognitive protection, we provide an overview of the association between AF and cognitive impairment and the potential mechanisms underlying this association. In addition, the effectiveness of AF-related treatment strategies, including anticoagulation, sinus rhythm restoration through elective cardioversion and catheter ablation, for cognitive protection in patients with AF is also discussed in this review.

Clinical Outcome of Intravenous Alteplase Treatment in Patients With Acute Mild Cerebral Infarction

ABSTRACTBackgroundThe efficacy of intravenous alteplase therapy for acute cerebral infarction is well established, regardless of the ischemic stroke subtype. However, its effectiveness in patients with mild cerebral infarction remains controversial, raising concerns about the significance of the treatment.AimTo retrospectively evaluate the efficacy of intravenous alteplase in patients with mild cerebral infarction and other factors affecting the outcome.MethodsA total of 527 patients received intravenous alteplase (0.6 mg/kg) at our hospital between October 2012 and March 2023. Of these, 118 patients with mild cerebral infarction (National Institutes of Health Stroke Scale [NIHSS] ≤ 5) who were treated with intravenous alteplase without mechanical thrombectomy were retrospectively evaluated for treatment efficacy and the factors affecting the efficacy.ResultsThe modified Rankin scale (mRS) outcome at 90 days was good (mRS: 0–1) in 85 (72%) patients and poor (mRS: 2–5) in 33 (28%) patients. Branch atheromatous disease (BAD) and proximal anterior circulation large vessel occlusion (proximal LVO: internal carotid artery and M1 segment of middle cerebral artery) were observed more frequently in the poor outcome group than in the good outcome group. Multivariate analysis, adjusted for age and sex, identified BAD and proximal LVO as factors associated with poor outcomes after intravenous alteplase treatment for mild cerebral infarction. Symptomatic intracranial hemorrhage was observed in one patient with BAD.ConclusionMost patients with mild cerebral infarction who were treated with intravenous alteplase alone had good outcomes. BAD and proximal LVO were other factors influencing poor outcomes.

Prolonged venous transit is associated with lower odds of excellent recovery after reperfusion in anterior large-vessel occlusion stroke.

Acute ischemic stroke due to anterior circulation large-vessel occlusion (AIS-LVO) remains a leading cause of disability despite successful reperfusion therapies. Prolonged venous transit (PVT) has emerged as a potential prognostic imaging biomarker in AIS-LVO. We aimed to investigate whether PVT is associated with a decreased likelihood of excellent functional outcome (modified Rankin Scale [mRS] score of 0-1 at 90 days) after successful reperfusion. In our prospectively collected, retrospectively reviewed database, we analyzed data from 104 patients with AIS-LVO who achieved successful reperfusion (modified Thrombolysis in Cerebral Infarction score of 2b/2c/3) between September 2017 and September 2022. PVT was defined as a time to maximum (Tmax) of ≥10 s in the superior sagittal sinus and/or torcula on computed tomography perfusion (CTP) imaging. Patients were categorized into PVT-positive (PVT+) and PVT-negative (PVT-) groups. The primary outcome was excellent functional recovery at 90 days. Of the 104 patients, 30 (29%) were PVT+. Excellent functional outcome was achieved in 38 patients (37%). PVT+ patients had a significantly lower rate of excellent recovery compared to PVT- patients (11% vs. 39%; p < 0.001). After adjusting for possible confounders, PVT positivity was independently associated with lower odds of excellent recovery (adjusted odds ratio 0.11, 95% confidence interval 0.02 to 0.48; p = 0.006). Among patients with AIS-LVO who achieved successful reperfusion, PVT positivity was independently associated with a decreased likelihood of excellent functional outcome at 90 days. Assessment of PVT on CTP may provide valuable prognostic information and aid in clinical decision making for patients with AIS-LVO.

Transient cerebral ischemia in pituitary apoplexy-induced internal carotid artery occlusion: illustrative case.

Cerebral ischemia secondary to occlusion or vasospasm of adjacent large vessels is a rare but significant complication of pituitary apoplexy. Misdiagnosis can lead to delays in management and devastating neurological outcomes. This case is the first reported instance of an initial presentation with transient cerebral ischemic symptoms, in addition to a classic pituitary apoplexy syndrome, for this clinical entity of pituitary apoplexy with adjacent large vessel occlusion. A 49-year-old man presented with a classic pituitary apoplexy syndrome of headache, vomiting, and hemianopia, with transient preceding expressive dysphasia and right-hand numbness. Computed tomography (CT) and CT angiography of the brain demonstrated a large apoplectic pituitary tumor and associated occlusion of the left internal carotid artery. Subsequent CT perfusion studies revealed a threatening large ischemic penumbra in the left middle cerebral artery territory. He underwent urgent transsphenoidal resection of the pituitary tumor, resulting in symptom resolution and the prevention of cerebral infarction. The recognition of transient cerebral ischemic symptoms in pituitary apoplexy should encourage the exclusion of any large-vessel complications and resultant cerebral ischemia. Early assessment, particularly with angiography and perfusion studies, can assist in guiding management, which is usually surgical decompression, distinct from traditional treatment for cerebrovascular events. https://thejns.org/doi/10.3171/CASE24566.

Safety and effectiveness of Salvia miltiorrhiza and ligustrazine injection for acute cerebral infarction in Chinese population: a PRISMA-compliant meta-analysis

BackgroundSalvia miltiorrhiza and ligustrazine injection (SML) is a type of traditional Chinese medicine injection, which has been considered a promising adjunctive therapy treatment for acute cerebral infarction (ACI). Although there have been positive reports on the treatment of SML, there is still controversy over its exact efficacy and safety in ACI patients. In this study, a systematic review was conducted on randomized controlled trials (RCTs) of SML for the treatment of ACI to evaluate its clinical efficacy and safety.MethodFrom the establishment of the database until May 2023, all randomized controlled trials related to SML and ACI were collected from the Cochrane Library, Web of Science, Embase, Medline, PubMed, CSJD, Wanfang database, CBM and CNKI. This systematic review and meta-analysis were strictly conducted in accordance with the PRISMA statement. The reported outcomes including overall response (ORR), National Institutes of Health Stroke Scale (NIHSS), hemorrheology indexes, activity of daily living (ADL) and adverse events were in detail investigated.ResultsAn analysis was conducted on the relevant data of 3869 ACI patients from 38 trials. The results indicated that the combination of conventional treatment and SML can significantly improve the ORR of patients (RR = 1.23, 95% CI = 1.20–1.27, P &amp;lt; 0.00001), neurological status (NIHSS, MD = −4.35, 95% CI = −5.15–3.54, P &amp;lt; 0.00001) and ADL (Barthel Index score, MD = 10.27, 95% CI = 7.75–12.79, P &amp;lt; 0.00001) compared with regular treatment alone. After the combined therapy, the hemorheology of ACI patients also significantly improved (P &amp;lt; 0.05). There is no significant difference in the frequency of adverse events between the two groups (RR = 1.49, 95% CI = 0.91–2.46, P = 0.11).ConclusionThe evidence from the meta-analysis suggested that the combination of conventional therapy and SML is safer and more effective than conventional therapy alone in treating ACI. However, due to the limitations of this analysis, such as regional bias and publication bias, the above conclusions need to be further verified by prospective, high-quality and multicenter clinical trials.

Kissing balloon treatment for stenosis of the internal and external carotid artery orifice associated with moyamoya disease: illustrative case.

Moyamoya disease (MMD) is a cerebrovascular disorder that is characterized by progressive stenosis in the terminal portions of the internal carotid artery (ICA). Although a substantial number of patients with MMD exhibit stenosis of the ICA orifice (ICAO), it infrequently occurs in patients with MMD with external carotid artery orifice (ECAO) stenosis. A 48-year-old female with no past medical history presented to the authors' hospital with right hemiparesis and motor aphasia. Head magnetic resonance imaging revealed bilateral acute cerebral infarctions in the left frontal lobe, and magnetic resonance angiography demonstrated bilateral ICA terminal stenosis. Digital subtraction angiography revealed severe stenosis in the right ICAO and left ICAO and ECAO, as well as bilateral ICA terminal stenosis; therefore, the authors diagnosed this case as MMD. They first performed percutaneous transluminal angioplasty (PTA) using the kissing balloon technique (KBT) for the stenosis in the left ICAO and ECAO, followed by PTA for the right ICAO stenosis. After that, they performed bilateral direct and indirect revascularization. The authors present a rare case of MMD with stenosis of the ICAO and ECAO, which was treated with PTA using the KBT, followed by direct and indirect revascularization. Although the strategy is controversial in terms of which treatment should be performed first, this method of anterograde revascularization was a promising strategy. https://thejns.org/doi/10.3171/CASE24425.

Endovascular treatment of non-acute symptomatic anterior circulation distal medium artery disease

Objective: To examine the clinical effect of endovascular treatment for patients with non-acute symptomatic anterior circulation distal medium artery disease (aDMAD). Methods: This is a retrospective case series study.Retrospective analysis was conducted on the clinical data of 28 patients(29 lesions) with non-acute symptomatic aDMAD who underwent endovascular treatment at the Department of Neurosurgery,Beijing Hospital from May 2018 to March 2024. There were 15 males and 13 females,with an age of (63.4±10.2) years (range:36 to 82 years). The course of disease were more than 72 hours of all the patients. Confirmed by digital subtraction angiography,the lesion was located in distal anterior circulation and (or) medium arteries. Among them, 21 lesions (72.4%) located at middle cerebral artery and 8 lesions (27.6%) located at anterior cerebral artery.The median degree of stenosis before surgery (M(IQR)) was 90%(23%) (range:70% to 100%).After standardized drug treatment,there was still a transient ischemic attack or cerebral infarction in the vascular related area.The therapeutic effects and complications were analyzed,and the differences in the occurrence of target vessel restenosis under different interventional treatment methods were collected. Results: A total of 28 patients with 29 lesions underwent endovascular treatment, with a treatment success rate of 96.6% (28/29). The course of disease was 60(66)days (range:9 to 210 days). Simple plain balloon angioplasty was performed in 12 cases (13 lesions), drug-coated balloon (DCB) angioplasty in 7 cases (7 lesions), and stent placement in 9 cases (9 lesions). The median degree of stenosis after surgery was 20%(39%) (range:0 to 50%). There was no new cerebral infarctions,cerebral hemorrhages,or other complications during the perioperative period.Imaging follow-up was conducted on 23 lesions for 12(15)months(range:3 to 34 months),with 10 cases (43.5%) of restenosis,3 cases (13.0%) of symptomatic restenosis,and 4 cases (17.4%) of re-treatment. There were no new cases of cerebral hemorrhage or death during the follow-up process.The restenosis rate was 6/10 for the conventional balloon group,1/6 for the DCB group, and 3/7 for the stent group; the rate of symptomatic restenosis was 1/10 for the conventional balloon group,0/6 for the DCB group, and 2/7 for the stent group. Conclusions: Endovascular treatment for non-acute symptomatic aDMAD is relatively effective,but there is a high rate of restenosis postoperatively. DCB may reduce the occurrence of postoperative restenosis.

METTL3 inhibits microglial pyroptosis in neonatal hypoxia-ischemia encephalopathy by regulating GPR39 expression in an m6A-HuR-dependent manner

BackgroundNeonatal hypoxia–ischemia encephalopathy (HIE) is a significant reason for neonatal mortality and prolonged disability. We have previously revealed that GPR39 activation attenuates neuroinflammation in a neonatal HIE rat model. This study aimed to investigate whether GPR39 affected microglial pyroptosis post-HIE. MethodsA neonatal rat model of HIE and a microglia cell model of oxygen-glucose deprivation (OGD) were established. Neuronal loss and cerebral infarction were assessed by using TTC, H&E staining, and Nissl staining. Pyroptosis was evaluated with western blot, LDH assay kit, ELISA, and flow cytometry. Total m6A level and GPR39 m6A modification were determined using m6A dot blot and MeRIP. The interaction between METTL3/HuR/GSK3β and GPR39 was analyzed by performing molecular interaction experiments. GPR39 mRNA stability was examined with actinomycin D. ResultsThe level of GPR39 was increased in neonatal HIE rats and OGD-treated microglia. Brain injury and neuronal loss were significantly increased in the HIE model when GPR39 was knocked down. GPR39 knockdown aggravated NLRP3 inflammasome-mediated microglial pyroptosis. METTL3 upregulated GPR39 expression in an m6A-dependent manner. METTL3 enhanced the interaction of HuR and GPR39. In OGD-exposed microglia, METTL3 elevated GPR39 expression and mRNA stability, which declined after HuR depletion. METTL3 knockdown promoted microglial pyroptosis, which was reversed by GPR39 agonist. Furthermore, microglial pyroptosis was inhibited by GPR39 upregulation, but the outcome was reverted by GSK3β activator SNP. ConclusionMETTL3 inhibits microglial pyroptosis in neonatal HIE via regulating m6A-HuR dependent stabilization of GPR39, which contributes to therapeutics development for neonatal HIE.

Letter to the Editor Regarding “Functional Outcome and Mortality Predictors in Patients with Cerebral Ischemic Infarction After Decompressive Craniectomy: Cross-Sectional Study”

Letter to the Editor Regarding “Functional Outcome and Mortality Predictors in Patients with Cerebral Ischemic Infarction After Decompressive Craniectomy: Cross-Sectional Study”

Preparation, Characterization, and Evaluation of Mesoporous Silica Nanoparticles in Enhancing Oral Bioavailability of Poorly Water-Soluble Drugs.

Breviscapine (BVP) is one of the extracts of several flavonoids of Erigeron breviscapus, which has been widely used in the treatment of cerebral infarction and its sequelae, cerebral thrombus, coronary heart disease, and angina pectoris. But BVP has poor solubility. The objective of the study is to develop mesoporous silica nanoparticles (MSNs) that can be loaded with a drug with poor water solubility. The MSNs, which were designed for oral administration, enhanced both the dissolution rate and drug loading capacity. The use of MSNs as an oral drug delivery system was investigated by SEM, TEM, BETBJH, XRD, FT-IR, and HPLC. Additionally, we examined the oral bioavailability of BVP loaded onto MSNs and examined the cellular cytotoxicity of MSNs. The results indicate that the oral bioavailability of BVP after loading onto MSNs was greater than that of a marketed product. Furthermore, we studied the mechanism by which MSNs enhance the oral absorption of BVP. MSNs have the potential to enhance the oral bioavailability of poorly water-soluble drugs by accelerating the drug dissolution rate.

Cerebral hemodynamics and oxygen metabolism in patients with milder and severe forms of sickle cell disease and thalassemia.

Silent cerebral infarcts (SCIs) are present in patients with sickle cell disease (SCD) and thalassemia, but the pathophysiology of SCIs is not fully understood. Previous studies mainly focused on cerebral hemodynamics and oxygen metabolism in patients with severe SCD (HbSS/HbSβ°) but not in milder forms of SCD (HbSC/HbSβ+) and thalassemia despite the high prevalence of SCIs in these patients. In this work, we studied the cerebral hemodynamics and oxygen metabolism, and SCI lesion load in 75 severe and 26 mild adult SCD patients, 18 thalassemia patients (as anemic comparison group), and 30 healthy controls before and after a vasodilatory challenge with acetazolamide. Cerebral blood flow was significantly higher in patients with severe SCD and thalassemia compared to patients with mild SCD and controls (p < 0.05). Conversely, oxygen extraction fraction and cerebral metabolic rate of oxygen (CMRO2) were significantly lower in patients with severe SCD and thalassemia compared to other groups (p < 0.01). In contrast, no difference in SCI volumes was found between mild and severe SCD and thalassemia patients. After acetazolamide administration, oxygen delivery increased less in severe SCD and thalassemia patients compared to other groups (p < 0.01) and CMRO2 decreased only in severe SCD patients (p < 0.01). Given the reduced CMRO2 values in severe SCD and thalassemia patients, we conclude that reduced cerebral oxygen consumption in these patient groups is mostly related to anemia. Our data suggest that the pathophysiology of SCIs in patients with milder forms of SCD might be more related to prior episodes of anemia or other sickle cell-related factors.

Scalp acupuncture alleviates remote hippocampal damage in MCAO rats by inhibiting neuroinflammation: A TMT-based proteomics analysis

While mounting evidence suggests that scalp acupuncture (SA) may be effective in alleviating neurological deficits in patients with acute ischemic stroke (IS), its effect on remote hippocampal damage in acute IS and the underlying mechanisms remain elusive. Thus, proteomics analysis was conducted to identify potential targets of SA therapy in acute IS. SA significantly reduced cerebral infarct volume and attenuated neuronal damage in the ischemic penumbra and hippocampus, as well as alleviated neurological deficits in rats with middle cerebral artery occlusion (MCAO). Moreover, 74 upregulated and 50 downregulated proteins were identified in the MCAO group compared to the sham group, whilst 52 up-regulated and 50 down-regulated proteins were identified in the SA group compared to the MCAO group. Bioinformatics analysis indicated that SA may exert neuroprotective effects by modulating the acute inflammatory response and microglial activation. Additionally, SA down-regulated the expression levels of Iba-1, TNF-α, IL-1β, and IL-6, while up-regulating those of IL-4 and IL-10. Likewise, it downregulated the expression levels of three key proteins identified via proteomics analysis (Kng1, Brd9, and Magl) that may mediate the anti-inflammatory effects of SA. Overall, these results indicate that SA attenuates neuronal damage in the hippocampus and ischemic penumbra and ameliorates neurological deficits. Proteomic analysis suggested that this effect is related to the modulation of the acute inflammatory response. SA attenuated remote hippocampal damage after IS by inhibiting microglia activation and neuroinflammation. Lastly, Kng1, Brd9, and Magl were identified as potential targets that mediate the anti-inflammatory effects of SA.

Protective effects of puerarin combined with bone marrow mesenchymal stem cells on nerve injury in rats with ischemic stroke

ABSTRACT Background Bone marrow mesenchymal stem cells (BM-MSCs) transplantation shows promise for treating ischemic stroke, but the ischemic environment that follows cerebral infarction hinders the survival of transplanted cells. We aimed to study the effects of puerarin (Pue) in combination with BM-MSCs on cerebral ischemic injury. Methods After middle cerebral artery occlusion (MCAO) models were prepared by suture-occluded method, rats were randomly allocated to the sham, MCAO, Pue (50 mg/kg), BM-MSCs (2×106), and BM-MSCs+Pue groups. The neurological function, infarct area, levels of inflammation-related factors, brain tissue damage, apoptosis, BrdU, Beclin1, and LC3 levels were then assessed. Results Pue and BM-MSCs reduced the modified neurological severity score, cerebral infarction area, and serum inflammation-related factor levels for MCAO rats. Furthermore, Pue and BM-MSCs interventions ameliorated brain tissue damage, and repressed apoptosis of brain tissues in MCAO rats. Moreover, Pue or BM-MSCs enhanced BrdU expression, restrained LC3II/LC3I ratio and Beclin 1 expression in MCAO rats’ brain tissues. Importantly, the combination of Pue and BM-MSCs exhibited more pronounced effects on aforementioned outcomes. Conclusion The combination of Pue and BM-MSCs facilitated the recovery of neurological function in rats after cerebral ischemic damage, and the mechanisms may correlate with the repression of neuronal apoptosis, inflammation, and autophagy.

Synergistic effects of repeated transcranial magnetic stimulation and mesenchymal stem cells transplantation on alleviating neuroinflammation and PANoptosis in cerebral ischemia

BackgroundNeuronal death is the primary cause of poor outcomes in cerebral ischemia. The inflammatory infiltration in the early phase of ischemic stroke plays a vital role in triggering neuronal death. Either transplantation of mesenchymal stem cells (MSCs) derived from humans or repetitive transcranial magnetic stimulation (rTMS) have respectively proved to be neuroprotective and anti-inflammatory in cerebral ischemia. However, either treatment above has its limitations. Whether these two therapies have synergistic effects on improving neurological function and the underlying mechanisms remains unclear. This investigation aims to elucidate the synergistic effects and underlying mechanisms of MSCs combined with rTMS treatment on the neurological function recovery post-ischemia.MethodsA Sprague-Dawley rat model of cerebral infarction was induced via transient middle cerebral artery occlusion (tMCAO). The rats were divided into five groups (n = 50): sham, tMCAO, rTMS, MSCs, and MSCs + rTMS groups. Transplantation of human umbilical cord MSCs and rTMS intervention were performed 24 h post-stroke. Neurological function was further assessed via several behavioral tests and the 2,3,5-triphenyltetrazolium chloride (TTC) staining companied with Nissl staining were used to assess neuronal survival. TUNEL staining, western blotting, immunofluorescence, immunohistochemistry, ELISA, and flow cytometry were employed to measure the levels of neuroinflammation and PANoptosis. The molecular mechanisms underlying the special role of rTMS in the combined therapy were distinguished with transcriptome sequencing via PC12 cells in oxygen-glucose deprivation/reoxygenation (OGD/R) conditions.ResultsThe combined therapy efficiently reduced lesion volume and improved neuronal survival (P < 0.05), subsequently improving functional recovery after ischemic stroke. MSCs + rTMS treatment ameliorated the PANoptosis in neurons (P < 0.05), accompanied by decreased levels of inflammatory factors in the cerebral tissue and serum during the subacute phase of cerebral infarction. To further explore the roles of either therapy on synergistic effect, we found that the transplanted MSCs primarily localized in the spleen and reduced cerebral inflammatory infiltration after ischemia via suppressed splenic inflammation. Meanwhile, rTMS significantly protects neurons from PANoptosis in MSCs-inhibited inflammatory conditions by downregulating REST unveiled by transcriptome sequencing.ConclusionsOur study elucidates an unidentified mechanism by which the combination of MSCs and rTMS could synergistically promote neuronal survival and suppress neuroinflammation during the subacute phase of cerebral infarction, thus improving neurological outcomes. The downregulating REST induced by rTMS may potentially contribute to the neuroprotective effect against PANoptosis in MSCs-inhibited inflammatory conditions. These results are expected to provide novel insights into the mechanisms of MSCs and rTMS combination therapy in synergistically protecting against cerebral ischemia injury and potential targets underlying neuronal PANoptosis in the early phase of stroke.

Cervical cancer with patent foramen ovale metastasis to the left ventricle: a case report

BackgroundMetastasis of malignant tumors to the cardiac endocardium is rare and mainly involves the right side of the heart. It is extremely rare to involve the left cardiac endocardium, especially when there is neither pulmonary metastasis nor primary lung cancer, which we call “isolated” left cardiac endocardium metastasis in this paper. Few such cases previously reported in the literature were not screened for patent foramen ovale (PFO).Case presentationThis article reports a case of a young woman with a history of surgery for cervical cancer, who was transferred to our hospital with a suspected diagnosis of PFO after recent recurrent multiple cerebral infarctions. On admission, transthoracic echocardiography revealed multiple stringy vegetations in the left ventricle, which were subsequently removed surgically, with intraoperative confirmation of a patent foramen ovale and closure of it simultaneously. According to her medical history and pathological results, she was diagnosed with left ventricular metastasis of cervical cancer, a rare case of isolated left heart endocardium metastasis without previous pulmonary metastasis, presumably through the patent foramen ovale.ConclusionPFO may play an important role in the process of isolated left heart endocardium metastasis in patients with distant malignancies and paradoxical embolism. Screening for PFO in high-risk patients may have significant clinical significance.

Molecular mechanism of METTL14-mediated m6A modification regulating microglial function post ischemic stroke

This study explores the molecular mechanism of METTL14 regulating microglial function post ischemic stroke. A murine model was established by tMCAO. The neurological function was evaluated by mNSS. The cerebral infarct size and pathological changes were observed by TTC and H&E staining. M1 and M2 microglia in brain tissues were detected by flow cytometry. BV2 cells were subjected to OGD/R to establish an in vitro model. qRT-PCR and Western blot were used for detecting METTL14, PAX6, YTHDF2, TREM2, iNOS, and Arg1 expressions. The m6A level was quantitatively analyzed, and the binding of YTHDF2 or m6A to PAX6 was analyzed by RIP. PAX6 mRNA stability was assessed after actinomycin D treatment. ChIP was utilized for determining the enrichment of PAX6 on TREM2 promoter. The binding relationship between TREM2 and PAX6 was verified by dual-luciferase reporter assay. METTL14 was highly expressed after tMCAO, and silence of METTL14 alleviated symptoms of tmcao mice and promoted microglial M2 polarization. METTL14 enhanced PAX6 mRNA m6A modification to promote YTHDF2 binding to PAX6 mRNA and its degradation. PAX6 bound to TREM2 promoter and facilitated its transcription and expression. In conclusion, METTL14-mediated m6A modification aggravates ischemic stroke by promoting microglial M1 polarization via YTHDF2/PAX6/TREM2 axis.

A multicenter trial on the predictors of different subtypes of hemorrhagic infarction after thrombolysis

Worldwide, stroke is a leading cause of long-term disability in adults. Alteplase is the only approved treatment for acute ischemic stroke (AIS) and results in an improvement in a third of treated patients. Most studies evaluated the post-alteplase haemorrhagic transformation of brain infarction as a homogeneous entity but we evaluated the predictors of each subtype of haemorrhagic transformation of brain infarction. Our trial included 616 AIS alteplase-treated patients. We evaluated the ability of different risk factors, clinical presentation, and imaging features to predict different haemorrhagic transformation (HT) subtypes. HT was seen in 152 patients (24.7%), higher NIHSS, cardioembolic stroke and atrial fibrillation were independent predictors of all ECASS-based subtypes of hemorrhagic infarction, in addition, anterior-circulation stroke was an independent predictor of hemorrhagic infarction type 1 (odds ratio [OR], 11.04; 95% CI, 9.81 to 12.70; P-value > 0.001) and type2 (OR, 11.89; 95% CI, 9.79 to 14.44; P-value > 0.001), while older age was also an independent predictor of parenchymal hematoma type1 (OR, 1.312; 95% CI, 1.245 to 1.912; P-value 0.02). In AIS patients treated with alteplase in Egypt and Saudi Arabia, higher NIHSS, cardioembolic stroke and atrial fibrillation were independent predictors of all ECASS-based subtypes of hemorrhagic infarction; in addition, anterior-circulation stroke was an independent predictor of hemorrhagic infarction type 1 and 2, while older age was also an independent predictor of parenchymal hematoma type1. Trial registration: (clinicaltrials.gov NCT06337175), retrospectively registered on 29/03/2024.

Infective endocarditis causing recurrent cerebral infarction, cerebral hemorrhage and septic meningitis: A case report.

We reported a rare case of recurrent cerebral infarction, intracerebral hemorrhage, and purulent meningitis, culminating in the diagnosis of a young patient with infective endocarditis who had been treated in 3 hospitals for a long course of illness for 8 months prior to diagnosis. It aims to enhance clinicians' understanding of the neurological complications caused by infective endocarditis. A 25-year-old male, student, was hospitalized for an 8-hour history of speech impairment and drooling with dysphagia. Magnetic resonance imaging (MRI) showed massive cerebral infarction in the right frontotemporal and insular lobes, and the first diagnosis was "cerebral infarction." Later, the patient developed recurrent cerebral infarction, intracerebral hemorrhage, and purulent meningitis. Recurrent cerebral infarction, intracerebral hemorrhage, and purulent meningitis were confirmed to be caused by infective endocarditis. The patient was treated with antiplatelet drugs such as aspirin and clopidogrel, mannitol to reduce intracranial pressure, and ceftriaxone and vancomycin to fight infection, and the patient's condition improved. The patient was diagnosed with infective endocarditis after 8 months without a clear diagnosis, and the patient was finally diagnosed with infective endocarditis during the final follow-up. Febrile patients should be aware of infective endocarditis, particularly if the fever is persistent of unknown origin or structural changes in the heart with neurologic lesions. Cardiogenic neurological diseases are relatively more severe, have a worse prognosis, and have a higher recurrence rate than primary neurological diseases, so early diagnosis and treatment are more urgently needed.

Differential analysis of microRNAs in plasma exosomes in patients with cerebral ischemic stroke.

The high incidence, disability, mortality, and recurrence rates of cerebral infarction impose a heavy burden on both the Chinese and global populations. It is essential for the early diagnosis, prevention, and protection against brain cell injury. To identify differentially expressed microRNAs (miRNAs) in plasma exosomes of patients with cerebral ischemic stroke, determine relevant biomarkers, and explore their potential signaling pathways. High-throughput sequencing was used to detect the expression of plasma exosomal miRNAs in patients with cerebral ischemic stroke and in a control group. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes enrichment, and target gene network analyses were performed to investigate the target genes and signaling pathways of the differentially expressed miRNAs. The sequencing results identified 95 differentially expressed miRNAs, with 40 upregulated and 55 downregulated miRNAs. Among these, hsa-miR-1303, hsa-miR-125b-1-3p, and hsa-miR-548ab were significantly upregulated in the stroke group and downregulated in the normal control group, whereas hsa-miR-1289 was downregulated in the stroke group and upregulated in the normal group. Gene Ontology, Kyoto Encyclopedia of Genes, and genomes enrichment analyses indicated that the differentially expressed miRNAs and their target genes were mainly concentrated in the PI3K-AKt, mitogen-activated protein kinase, calcium, Ras, Rap1, and cAMP signaling pathways. The expression of plasma exosomal hsa-miR-1303, hsa-miR-125b-1-3p, and hsa-miR-1289 was significantly different in stroke patients than in the control group. These miRNAs may be involved in various signaling pathways related to cerebral infarction, providing a reference for further experimental research.

One in six patients exhibit changes in reperfusion on 10-minute repeat cerebral angiography during mechanical thrombectomy for stroke

BackgroundPost-recanalization target vessel re-occlusion (TVR) following endovascular thrombectomy (EVT) is a known complication of the procedure, and it is associated with worse long-term functional outcomes. The incidence and factors that...