Intensive Ambulance-Delivered Blood-Pressure Reduction in Hyperacute Stroke.

BACKGROUND: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain. METHODS: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group). The primary efficacy outcome was functional status as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days after randomization. The primary safety outcome was any serious adverse event. RESULTS: A total of 2404 patients (mean age, 70 years) in China underwent randomization and provided consent for the trial: 1205 in the intervention group and 1199 in the usual-care group. The median time between symptom onset and randomization was 61 minutes (interquartile range, 41 to 93), and the mean blood pressure at randomization was 178/98 mm Hg. Stroke was subsequently confirmed by imaging in 2240 patients, of whom 1041 (46.5%) had a hemorrhagic stroke. At the time of patients' arrival at the hospital, the mean systolic blood pressure in the intervention group was 159 mm Hg, as compared with 170 mm Hg in the usual-care group. Overall, there was no difference in functional outcome between the two groups (common odds ratio, 1.00; 95% confidence interval [CI], 0.87 to 1.15), and the incidence of serious adverse events was similar in the two groups. Prehospital reduction of blood pressure was associated with a decrease in the odds of a poor functional outcome among patients with hemorrhagic stroke (common odds ratio, 0.75; 95% CI, 0.60 to 0.92) but an increase among patients with cerebral ischemia (common odds ratio, 1.30; 95% CI, 1.06 to 1.60). CONCLUSIONS: In this trial, prehospital blood-pressure reduction did not improve functional outcomes in a cohort of patients with undifferentiated acute stroke, of whom 46.5% subsequently received a diagnosis of hemorrhagic stroke. (Funded by the National Health and Medical Research Council of Australia and others; INTERACT4 ClinicalTrials.gov number, NCT03790800; Chinese Trial Registry number, ChiCTR1900020534.).

Deep learning-based magnetic resonance imaging analysis for chronic cerebral hypoperfusion risk.

BACKGROUND: Chronic cerebral hypoperfusion (CCH) is a frequently encountered clinical condition that poses a diagnostic challenge due to its nonspecific symptoms. PURPOSE: To enhance the diagnosis of CCH and non-CCH through Magnetic Resonance Imaging (MRI), offering support in clinical decision-making and recommendations to ultimately elevate diagnostic accuracy and optimize patient treatment outcomes. METHODS: In the retrospective research, we collected 204 routine brain magnetic resonance imaging (MRI) from March 1 to September 10 2022, as training and testing cohorts. And a validation cohort with 108 samples was collected from November 14 2022 to August 4 2023. MRI sequences were processed to obtain T1-weighted (T1WI) and T2-weighted (T2WI) sequence images for each patient. We propose CCH-Network (CCHNet), an end-to-end deep learning model, integrating convolution and Transformer modules to capture local and global structural information. Our novel adversarial training method improves feature knowledge capture, enhancing both generalization ability and efficiency in predicting CCH risk. We assessed the classification performance of the proposed model CCHNet by comparing it with existing state-of-the-art deep learning algorithms, including ResNet34, DenseNet121, VGG16, Convnext, ViT, Coat, and TransFG. To better validate model performance, we compared the results of the proposed model with eight neurologists to evaluate their consistency. RESULTS: CCHNet achieved an AUC of 91.6% (95% CI: 86.8-99.1), with an accuracy (ACC) of 85.0% (95% CI: 75.6-95.2). It demonstrated a sensitivity (SE) of 80.0% (95% CI: 71.6-95.6) and a specificity (SP) of 90.0% (95% CI: 82.3-97.8) in the testing cohort. In the validation cohort, the model demonstrated an AUC of 86.0% (95% CI: 80.3-93.0), an ACC of 84.2% (95% CI: 70.2-93.6), a SE of 83.3% (95% CI: 68.3-95.5), and a SP of 84.7% (95% CI: 70.3-96.8). CONCLUSIONS: The model improved the diagnostic performance of MRI with high SE and SP, providing a promising method for the diagnosis of CCH.

Predictive role of neutrophil-to-platelet ratio in futile recanalization of patients after endovascular therapy.

Aim: To explore the association between the neutrophil-to-platelet ratio (NPR) and futile recanalization (FR) in patients with acute ischemic stroke due to large vascular occlusions after endovascular therapy (EVT). Methods: FR after EVT was defined as a poor 90-day prognosis (modified Rankin scale [mRS] score ≥3) despite successful reperfusion (modified thrombolysis in cerebral infarction grade 2b-3). Patients were divided into high NPR (>35; n = 115) and low NPR (≤35; n = 81) groups. Results: The FR rate was significantly higher in the high NPR group than low NPR group (81.74 vs 55.56%; p = 0.000). NPR was independently associated with FR (odds ratio: 2.107; 95% CI: 1.017-4.364; p = 0.045). Conclusion: High NPR was associated with the risk of FR in patients with acute ischemic stroke due to large vascular occlusions.

Predictive Role of Pre-Thrombolytic Neutrophil-Platelet Ratio on Hemorrhagic Transformation After Intravenous Thrombolysis in Acute Ischemic Stroke.

To investigate the predictive role of the neutrophil-platelet ratio (NPR) before intravenous thrombolysis (IVT) on hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS). AIS patients treated with IVT without endovascular therapy between June 2019 and February 2023 were included. Patients were divided into high NPR (>35) and low NPR (≤35) groups according to the optimal threshold NPR value for identifying high-risk patients before IVT. The baseline data and the incidence of HT and symptomatic intracranial hemorrhage (sICH) were compared between the two groups. The predictive role of the NPR and other related factors on HT after IVT was analyzed by multivariate logistic regression. A total of 247 patients were included, with an average age of 67.5 ± 12.4 years. Post-thrombolytic HT was observed in 18.6% of the patients, and post-thrombolytic sICH was observed in 1.2% of the patients. There were 69 patients in the high NPR group and 178 patients in the low NPR group. The incidence of HT in the high NPR group was significantly higher than that in the low NPR group (30.4% vs 16.3%, P < .05). The incidence of sICH was significantly higher in the high NPR group than in the low NPR group (14.5% vs 1.7%, P < .001). Multivariate logistic regression analysis showed that NPR > 35 was positively correlated with HT (odds ratio (OR) = 3.236, 95% confidence interval (CI): 1.481-7.068, P = .003) and sICH (OR = 13.644, 95% CI: 2.392-77.833, P = .003). A high NPR (>35) before IVT may be a predictor of HT in AIS patients. This finding may help clinicians make clinical decisions before IVT in AIS patients.

Glucocorticoid-dependent multiple sclerosis overlapping anti-NMDA receptor encephalitis: a case report and literature review update.

BACKGROUND: Previous studies suggest a relationship between central nervous system inflammatory demyelinating diseases and anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. Also, the overlap between anti-NMDAR encephalitis and multiple sclerosis (MS) has been reported. However, the pathogenesis and clinical characteristics are still obscure. CASE PRESENTATION: A 33-year-old woman presented with diplopia and sensory ataxia at the onset. The cerebrospinal fluid (CSF) anti-NMDAR antibodies were positive (1:3.2), and nuclear magnetic resonance imaging (MRI) showed bilateral centrum ovale and lateral ventricle demyelinating lesions. Therefore, she was diagnosed with anti-NMDAR encephalitis. After administering intravenous immunoglobulin and oral prednisone, her lesions disappeared, and symptoms were relieved. The condition was maintained with a low dose of prednisone, but her lesions reappeared on MRI. Consequently, immunomodulatory therapy of mycophenolate mofetil was initiated. However, she developed dysarthria and right limb ataxia after 10 months with a positive CSF anti-NMDAR antibody (1:1) and positive oligoclonal band. The MRI showed symmetrical multiple demyelinating lesions. Considering the MS diagnosis, her neurological dysfunction again improved significantly after intravenous methylprednisolone. Unfortunately, her symptoms aggravated for the second time when teriflunomide was started. Finally, her condition was controlled again with oral prednisone. CONCLUSIONS: Consistent with previous cases of overlapping anti-NMDAR encephalitis and MS, patients often show atypical symptoms on MRIs and immunological tests. The overlap cannot be arbitrarily treated because of the recurrence of previous diseases. Long-term follow-up, dynamic antibody monitoring, and MRI examination are crucial for these patients. The special dependency of the patient on glucocorticoids in this study has been rarely reported, which may guide the treatment of insensitivity to disease-modifying therapy in recurrent overlapping anti-NMDAR encephalitis and MS.

Traditional Chinese medicine alleviating neuropathic pain targeting purinergic receptor P2 in purinergic signaling: A review.

Past studies have suggested that Chinese herbal may alleviate neuropathic pain, and the mechanism might target the inhibition of purinergic receptor P2. This review discusses whether traditional Chinese medicine target P2 receptors in neuropathic pain and its mechanism in order to provide references for future clinical drug development. The related literatures were searched from Pubmed, Embase, Sinomed, and CNKI databases before June 2023. The search terms included"neuropathic pain", "purinergic receptor P2", "P2", "traditional Chinese medicine", "Chinese herbal medicine", and "herb". We described the traditional Chinese medicine alleviating neuropathic pain via purinergic receptor P2 signaling pathway including P2X2/3 R, P2X3R, P2X4R, P2X7R, P2Y1R. Inhibition of activating glial cells, changing synaptic transmission, increasing painful postsynaptic potential, and activating inflammatory signaling pathways maybe the mechanism. Purine receptor P2 can mediate the occurrence of neuropathic pain. And many of traditional Chinese medicines can target P2 receptors to relieve neuropathic pain, which provides reasonable evidences for the future development of drugs. Also, the safety and efficacy and mechanism need more in-depth experimental research.

Cerebral blood volume index can predict the long-term prognosis after endovascular thrombectomy in patients with acute ischemic stroke due to large vessel occlusion.

Long-term prognosis and factors influencing endovascular therapy (EVT) remain unclear. This study aimed to investigate the association between computed tomography perfusion (CTP) parameters and long-term prognosis of patients with acute ischemic stroke (AIS) treated with EVT. Patients with AIS due to large vessel occlusion treated with EVT were prospectively included for a 1-year follow-up. All patients and their data were grouped based on the hypoperfusion intensity ratio (HIR, ＜0.3 vs. ≥ 0.3) and cerebral blood volume (CBV) index (＞0.7 vs. ≤ 0.7). The primary outcome was favorable prognosis, defined as a modified Rankin Scale (mRS) score of 0-2. Multivariate logistic regression was used to analyze factors influencing long-term favorable prognosis. Of 69 patients included, 35 (50.7 %) achieved mRS 0-2 at one year. A favorable prognosis was observed predominantly in patients with higher CBV index (75.0 % vs. 34.1 %, p= 0.001) and lower HIR (72.0 % vs. 38.6 %, p=0.008). In the multivariate logistic regression, CBV index (odds ratio (OR) = 4.362; 95 % confidence interval (CI): 1.052, 18.082; p = 0.042), baseline National Institutes of Health Stroke Scale (NIHSS) score (OR = 0.913; 95 % CI: 0.836, 0.997; p = 0.044), and symptomatic intracranial hemorrhage (sICH) (OR = 0.089; 95 % CI: 0.009, 0.925; p = 0.043) were independently associated with a long-term favorable prognosis. The CBV index may serve as a predictor of the long-term prognosis of patients treated with EVT. The novel finding is that the baseline NIHSS score and sICH were associated with long-term prognosis.

Association of ultra-processed foods consumption with risk of cardio-cerebrovascular disease: A systematic review and meta-analysis of cohort studies.

AIMS: The epidemiological evidence regarding the impact of ultra-processed foods (UPFs) on the risk of cardio-cerebrovascular diseases (CCVDs) is controversial. The aim of this systematic review and meta-analysis is to examine the association between UPF consumption and the risk of CCVDs within cohort studies. DATA SYNTHESIS: A systematic literature search was conducted across multiple databases, including PubMed/Medline, Embase, Web of Science, Scopus, and the Cochrane Library databases, covering the inception of these databases up until January 1st, 2023. A total of 39 cohort studies involving 63,573,312 human participants were deemed eligible according to the inclusion criteria. Utilizing random-effects models, risk ratios (RRs) were estimated to determine the pooled results. Our findings indicate a significant association between a higher consumption of UPF and an increased likelihood of CCVDs (RR: 1.08, 95% CI: 1.01-1.16, I2 = 89%; p < 0.01) compared to individuals who either abstain from or consume lesser amounts of UPF. Nonlinear dose-response meta-analyses showed that a consistent high intake of UPFs was associated with an elevated risk of developing CCVDs (p non-linearity <0.001). Notably, the risk of CCVDs escalated by approximately 7% with an UPF intake of up to 1 serving per day. Subgroup analysis further revealed a significant augmentation in the risk of total CVD and hypertension with increased UPF consumption. CONCLUSIONS: A higher intake of UPF significantly increases the risk of developing CCVDs. Prospective studies controlling for confounding factors are needed to validate the relationship between UPF intake and the development of CCVDs.

Direct Thrombectomy versus Bridging Thrombectomy within 6 Hours of Stroke Onset: A Prospective Cohort Study on Cognitive and Physical Function Outcomes.

PURPOSE: To evaluate the physical and cognitive functions of patients with stroke who underwent either direct or bridging thrombectomy within 6 hours of stroke onset. MATERIALS AND METHODS: Patients with large vessel occlusion in anterior circulation treated with direct (direct group) or bridging thrombectomy (bridging group) were prospectively analyzed between June 2020 and February 2022. The efficacy outcome was the 3-month modified Rankin Scale (mRS) score, the safety outcome was symptomatic intracranial hemorrhage (sICH), and cognitive function was assessed using the Clinical Dementia Rating (CDR) scale at 6 months after stroke. RESULTS: A total of 125 patients (direct group, n = 75; bridging group, n = 50) who had completed follow-up at 3 months by telephone call were included. No significant differences were observed between the direct and bridging groups in terms of an mRS score of 0-2 (25.3% vs 22.0%, respectively; P = .83), an mRS score of 0-3 (37.3% vs 44.0%, respectively; P = .58), sICH (17.3% vs 14.0%, respectively; P = .80), or 3-month all-cause mortality (36.3% vs 30.0%, respectively; P = .34). Sixty-nine patients (direct group, n = 38; bridging group, n = 31) completed the CDR assessment at 6 months after stroke. There was no significant difference in poststroke dementia, defined as a CDR score of ≥1 point between the direct group (42.1%) and bridging group (22.6%) (P = .12). Ordinal regression analyses showed that the CDR score at 6 months was not associated with treatment type (direct thrombectomy vs bridging thrombectomy). CONCLUSIONS: With regard to physical and cognitive functions at 3 and 6 months, direct thrombectomy was comparable with bridging thrombectomy in patients who were treated within 6 hours of stroke onset.

Predictive role of pre-thrombolytic hs-CRP on the safety and efficacy of intravenous thrombolysis in acute ischemic stroke.

PURPOSE: To investigate the predictive role of pre-thrombolytic high sensitivity C-reactive protein (hs-CRP) on the safety and efficacy of intravenous thrombolysis in patients with acute ischemic stroke (AIS). METHODS: Patients with AIS who underwent intravenous thrombolysis with recombinant plasminogen activator (rtPA) or urokinase without endovascular therapy from June 2019 to June 2022 were retrospectively analysed. All patients were grouped into two groups (high or low hs-CRP group) according to the median value of hs-CRP before intravenous thrombolysis. The baseline NIHSS, NIHSS changes before and after thrombolysis (ΔNIHSS), the rate of good thrombolysis response (NIHSS decreased ≥ 2 points from baseline), the rate of any intracranial hemorrhage, age, sex, hypertension, diabetes, uric acid and platelet count were compared between the two groups. Logistic regression analysis was performed to identify possible prognostic factors for a good thrombolysis response. RESULTS: A total of 212 patients were included in the analysis, with a mean age of 66.3 ± 12.5 years. In total, 145 patients received rtPA, and 67 patients received urokinase. Patients were divided into a high hs-CRP group (> 1.60 mg/L) and a low hs-CRP group (≤ 1.60 mg/L) according to the median hs-CRP level (1.60 mg/L). The ΔNIHSS of the high hs-CRP group was significantly smaller than that of the low hs-CRP group (0 [-1 ~ 0] vs. -1 [-2 ~ 0], P < 0.05). The good rate of thrombolysis response in the high hs-CRP group was significantly lower than that in the low hs-CRP group (21.9% vs. 36.5%, P < 0.05). Similar results were shown in the rtPA subgroup between the high and low hs-CRP groups but not in the urokinase subgroup. Logistic regression analysis showed that hs-CRP > 1.60 mg/L was negatively correlated with a good thrombolysis response rate (OR = 0.496, 95% CI = 0.266-0.927, P = 0.028). CONCLUSION: hs-CRP > 1.6 mg/L may serve as a poor prognosis predictive factor for patients with AIS receiving intravenous thrombolysis. However, due to the small sample size of this study, further studies are needed to verify our results.

Stigmasterol protects human brain microvessel endothelial cells against ischemia-reperfusion injury through suppressing EPHA2 phosphorylation.

Stigmasterol is a plant sterol with anti-apoptotic, anti-oxidative and anti-inflammatory effect through multiple mechanisms. In this study, we further assessed whether it exerts protective effect on human brain microvessel endothelial cells (HBMECs) against ischemia-reperfusion injury and explored the underlying mechanisms. HBMECs were used to establish an in vitro oxygen and glucose deprivation/reperfusion (OGD/R) model, while a middle cerebral artery occlusion (MCAO) model of rats were constructed. The interaction between stigmasterol and EPHA2 was detected by surface plasmon resonance (SPR) and cellular thermal shift assay (CETSA). The results showed that 10 µmol·L-1 stigmasterol significantly protected cell viability, alleviated the loss of tight junction proteins and attenuated the blood-brain barrier (BBB) damage induced by OGD/R in thein vitro model. Subsequent molecular docking showed that stigmasterol might interact with EPHA2 at multiple sites, including T692, a critical gatekeep residue of this receptor. Exogenous ephrin-A1 (an EPHA2 ligand) exacerbated OGD/R-induced EPHA2 phosphorylation at S897, facilitated ZO-1/claudin-5 loss, and promoted BBB leakage in vitro, which were significantly attenuated after stigmasterol treatment. The rat MCAO model confirmed these protective effects in vivo. In summary, these findings suggest that stigmasterol protects HBMECs against ischemia-reperfusion injury by maintaining cell viability, reducing the loss of tight junction proteins, and attenuating the BBB damage. These protective effects are at least meditated by its interaction with EPHA2 and inhibitory effect on EPHA2 phosphorylation.

Ginsenoside compound K reduces ischemia/reperfusion-induced neuronal apoptosis by inhibiting PTP1B-mediated IRS1 tyrosine dephosphorylation.

Background: Ginsenoside compound K (CK) stimulated activation of the PI3K-Akt signaling is one of the major mechanisms in promoting cell survival after stroke. However, the underlying mediators remain poorly understood. This study aimed to explore the docking protein of ginsenoside CK mediating the neuroprotective effects. Materials and methods: Molecular docking, surface plasmon resonance, and cellular thermal shift assay were performed to explore ginsenoside CK interacting proteins. Neuroscreen-1 cells and middle cerebral artery occlusion (MCAO) model in rats were utilized as in-vitro and in-vivo models. Results: Ginsenoside CK interacted with recombinant human PTP1B protein and impaired its tyrosine phosphatase activity. Pathway and process enrichment analysis confirmed the involvement of PTP1B and its interacting proteins in PI3K-Akt signaling pathway. PTP1B overexpression reduced the tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) after oxygen-glucose deprivation/reoxygenation (OGD/R) in neuroscreen-1 cells. These regulations were confirmed in the ipsilateral ischemic hemisphere of the rat brains after MCAO/R. Ginsenoside CK treatment reversed these alterations and attenuated neuronal apoptosis. Conclusion: Ginsenoside CK binds to PTP1B with a high affinity and inhibits PTP1B-mediated IRS1 tyrosine dephosphorylation. This novel mechanism helps explain the role of ginsenoside CK in activating the neuronal protective PI3K-Akt signaling pathway after ischemia-reperfusion injury.

Helicobacter pylori Infection Is Associated with Long-Term Cognitive Decline in Older Adults: A Two-Year Follow-Up Study.

BACKGROUND: Previous cross-sectional studies have identified a possible link between Helicobacter pylori (H. pylori) infection and dementia. However, the association of H. pylori infection with longitudinal cognitive decline has rarely been investigated. OBJECTIVE: This cohort study aims to demonstrate the effects of H. pylori infection on longitudinal cognitive decline. METHODS: This cohort study recruited 268 subjects with memory complaints. Among these subjects, 72 had a history of H. pylori infection, and the rest 196 subjects had no H. pylori infection. These subjects were followed up for 24 months and received cognitive assessment in fixed intervals of 12 months. RESULTS: At baseline, H. pylori infected, and uninfected participants had no difference in MMSE scores. At 2 years of follow-up, H. pylori infected participants had lower MMSE scores than uninfected participants. H. pylori infection was associated with an increased risk of longitudinal cognitive decline, as defined by a decrease of MMSE of 3 points or more during follow-up, adjusting for age, sex, education, APOEɛ4 genotype, hypertension, diabetes, hyperlipidemia, and smoking history (HR: 2.701; 95% CI: 1.392 to 5.242). H. pylori infection was associated with larger cognitive decline during follow-up, adjusting for the above covariates (standardized coefficient: 0.282, p < 0.001). Furthermore, H. pylori infected subjects had significantly higher speed of cognitive decline than uninfected subjects during follow-up, adjusting for the above covariates. CONCLUSION: H. pylori infection increases the risk of longitudinal cognitive decline in older subjects with memory complaints. This study is helpful for further understanding the association between infection and dementia.

Phthalide derivative CD21 regulates the platelet- neutrophil extracellular trap-thrombin axis and protects against ischemic brain injury in rodents.

Prothrombotic and proinflammatory properties of neutrophil extracellular traps (NETs) contribute to brain damage after ischemic stroke. CD21 is a novel phthalide neuroprotectant against cerebral ischemia in rodents. This study investigated effects of CD21 on the platelet-NET-thrombin axis and ischemic brain injury and the underlying mechanism. CD21 exerteddose-dependent neuroprotectionin rats that were subjected to2 h middle cerebral artery occlusion,dose-dependentlyinhibited adenosine diphosphate-mediatedplatelet aggregationin rats, and dose-dependentlyexertedanti-thrombotic activityin rodents that received a collagen-epinephrine combination, ferric chloride, or an arteriovenous shunt. Equimolar CD21 doses exerted stronger efficacy than 3-N-butylphthalide (NBP, natural phthalide for the treatment of ischemic stroke). CD21 dose-dependently improved regional cerebral blood flow, neurobehavioral deficits, and infarct volume in mice that were subjected to photothrombotic stroke (PTS). CD21 (13.79 mg/kg, i.v.) significantly decreased NET components (plasma dsDNA concentrations; mRNA levels of elastase, myeloperoxidase, and neutrophil gelatinase-associated lipocalin and protein level of citrullinated histone H3 in ischemic brain tissues), mRNA and protein levels of peptidyl-arginine deiminase 4 (PDA4, NET formation enzyme), and mRNA levels of NET-related inflammatory mediators (interleukin-1ß, interleukin-17A, matrix metalloproteinase 8, and matrix metalloproteinase 9) in ischemic brain tissues, despite no effect on mRNA levels of deoxyribonuclease I (NET elimination enzyme). Pretreatment with compound C (inhibitor of adenosine monophosphate-activated protein kinase [AMPK]) significantly reversed the inhibitory effects of CD21 on NETs, PDA4, and inflammatory mediators in PTS mice. These results suggest that CD21 might regulate the platelet-NET-thrombin axis and protect against ischemic brain injury partly through the induction of AMPK activation.

Anti-CASPR2 encephalitis in a liver posttransplant patient receiving immune-suppression and lenvatinib: a case report and literature review.

It has been assumed that patients with strict immunosuppressive treatment after solid organ transplantation have only marginal risk in developing autoimmune encephalitis. We reported a woman in her late 40 s who presented with generalized convulsions and loss of consciousness. After detailed history review, neuropsychological tests, metagenomic next-generation sequencing of serum and cerebrospinal fluid (CSF), magnetic resonance imaging (MRI) brain, and electroencephalogram, she was diagnosed as anti-CASPR2 encephalitis based on the positive anti-CASPR2 auto-antibody in serum and CSF. The patient underwent liver transplantation and has taken lenvatinib for 2 months, in addition to tacrolimus, mycophenotale mofetil, and entecavir administered for half a year. This case was the first report of anti-CASPR2 encephalitis in post-organ transplantation patients. Together with the reports of other encephalitis cases in organ transplantation, it warns the possibility of developing immune-oriented encephalitis in patients undergoing immunosuppression, especially in combination with other treatments of immunomodulatory activity.

Purinergic signaling: a potential therapeutic target for ischemic stroke.

Pathogenesis of ischemic stroke is mainly characterized by thrombosis and neuroinflammation. Purinergic signaling pathway constitutes adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine (ADO). ATP is hydrolyzed to ADP and then to AMP by extracellular nucleotidase CD39; AMP is subsequently converted to adenosine by CD73. All these nucleotides and nucleosides act on purinergic receptors protecting against thrombosis and inhibit inflammation. In addition, many physical methods have been found to play a neuroprotective role through purinergic signaling. This review mainly introduces the role and potential mechanism of purinergic signalings in the treatment of ischemic stroke, so as to provide reference for seeking new treatment methods for stroke.

The pathogenesis and treatment of posterior reversible encephalopathy syndrome after neuromyelitis optica spectrum disorder: a case report and literature review.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a rare disease characterized by reversible subcortical vasogenic brain edema. Neuromyelitis optica spectrum disorder (NMOSD) is a frequent neurological autoimmune disease that is rarely reported to complicate PRES. CASE PRESENTATION: Here, we report a case of neuromyelitis optica (NMO) concurrent with PRES. A 50-year-old woman presented with severe impairment of her health visual acuity, with significantly worsening of the motor weakness in both lower limbs during methylprednisolone therapy after her diagnosis of NMO. MRI showed new-onset brain edematous lesions of the bilateral frontal, occipital, and parietal lobes. PRES was considered. Her vision impairment and weakness of the extremities were alleviated after antihypertensive treatment and dehydration. The edema lesions detected by MRI also completely disappeared. CONCLUSIONS: We reviewed 14 cases of NMO with PRES and concluded that the etiology of NMOSD concurrent PRES may be multifactorial, involving pathogenic IgGs against aquaporin-4 (AQP-4) and immunotherapy treatment. Different underlying pathogeneses require different treatment approaches.

Neuroprotective effect of alpha-kinase 1 knockdown against cerebral ischemia through inhibition of the NF-κB pathway and neuroinflammation.

BACKGROUND: Activation of the nuclear factor B (NF-κB) signaling pathway by pattern recognition receptors (PRRs) is regarded as a crucial mechanism of neuroinflammation and brain injury after acute ischemic stroke. The stimulation of alpha-kinase 1 (ALPK1), a newly identified PRR, triggers NF-κB activation and an inflammatory response. Longitudinal population-based genetic epidemiological studies suggest that the ALPK1 gene is a susceptible site to ischemic stroke. However, the function of ALPK1 in the central nervous system remains unclear. The present study explored the role of ALPK1 in acute ischemic stroke. METHODS: BV2 microglial cells were stimulated with conditioned medium (CM) that was collected from oxygen and glucose deprivation (OGD)-treated HT22 neurons, and a murine brain ischemia model was established to detect the changes of ALPK1 expression. We used lentivirus to knockdown ALPK1 to explore the effects of ALPK1 in cerebral ischemia models in vitro and in vivo. RESULTS: We observed a significant increase of ALPK1 expression in BV2 cells that were stimulated with OGD CM. The knockdown of ALPK1 inhibited the phosphorylation of tumor necrosis factor receptor associated factor-interacting protein with a forkhead-associated domain (TIFA), the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), the activation of NF-κB, and the levels of proinflammatory factors in the BV2 cells. We also verified a neuroprotective effect of ALPK1 knockdown against ischemic brain injury through inhibition of the TIFA/TRAF6/NF-κB pathway and neuroinflammation in mice. CONCLUSIONS: This study demonstrates that ALPK1 is implicated in sterile inflammatory injury after acute brain ischemia, which provides first evidence for the therapeutic potential of ALPK1 inhibition in ischemic stroke.

Ginsenoside Rd protects cerebral endothelial cells from oxygen-glucose deprivation/reoxygenation induced pyroptosis via inhibiting SLC5A1 mediated sodium influx.

Background: Ginsenoside Rd is a natural compound with promising neuroprotective effects. However, the underlying mechanisms are still not well-understood. In this study, we explored whether ginsenoside Rd exerts protective effects on cerebral endothelial cells after oxygen-glucose deprivation/reoxygenation (OGD/R) treatment and its potential docking proteins related to the underlying regulations. Method: Commercially available primary human brain microvessel endothelial cells (HBMECs) were used for in vitro OGD/R studies. Cell viability, pyroptosis-associated protein expression and tight junction protein degradation were evaluated. Molecular docking proteins were predicted. Subsequent surface plasmon resonance (SPR) technology was utilized for validation. Flow cytometry was performed to quantify caspase-1 positive and PI positive (caspase-1+/PI+) pyroptotic cells. Results: Ginsenoside Rd treatment attenuated OGD/R-induced damage of blood-brain barrier (BBB) integrity in vitro. It suppressed NLRP3 inflammasome activation (increased expression of NLRP3, cleaved caspase-1, IL-1ß and GSDMD-N terminal (NT)) and subsequent cellular pyroptosis (caspase-1+/PI + cells). Ginsenoside Rd interacted with SLC5A1 with a high affinity and reduced OGD/R-induced sodium influx and potassium efflux in HBMECs. Inhibiting SLC5A1 using phlorizin suppressed OGD/R-activated NLRP3 inflammasome and pyroptosis in HBMECs. Conclusion: Ginsenoside Rd protects HBMECs from OGD/R-induced injury partially via binding to SLC5A1, reducing OGD/R-induced sodium influx and potassium efflux, thereby alleviating NLRP3 inflammasome activation and pyroptosis.

Cerebral blood volume index may be a predictor of independent outcome of thrombectomy in stroke patients with low ASPECTS.

INTRODUCTION: To evaluate the predictors for efficacy and safety of patients with acute ischemic stroke (AIS) and Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) ＜6 undergoing endovascular therapy (EVT). METHODS: This study retrospectively analyzed consecutive patients presented between December 2020 and December 2021 with large vessel occlusions (LVO) within the anterior circulation and an ASPECTS ＜6, followed by EVT. The efficacy outcome was 90-day functional independence, defined as modified Rankin Scale (mRS) score 0-3. The primary safety outcome was symptomatic intracranial hemorrhage (sICH). Secondary safety outcomes included 90-day all-cause mortality and 24-hour any ICH. RESULTS: A total of 22 patients were included. The percentage of patients with mRS 0-3 at 90 days was 36.4% (8/22). The occurrence of sICH was 22.7% (5/22). The occurrence of any ICH was 45.5% (10/22). The 90-day all-cause mortality was 36.4% (8/22). Median (interquartile range, IQR) cerebral blood volume (CBV) index was 0.5 (0.4-0.7). CBV index in mRS 0-3 group (n = 8) was higher than mRS 4-5 group (n = 14) (P＜0.05). There was no significant difference of age, gender, comorbidities, baseline National Institutes of Health Stroke Scale (NIHSS) score, mismatch ratio, CBV index, interval between stroke onset and re-perfusion, good re-perfusion rate between sICH group (n = 5) and non-sICH group (n = 17). CONCLUSIONS: AIS patients with low ASPECTS can still benefit from EVT and gain good functional outcome, especial those had higher CBV index on pre-EVT computed tomography perfusion (CTP). Further studies with larger sample size are needed to validate our findings.