Cerebral Infarction Research Articles

Neuroplasticity-enhancing therapy using glia-like cells derived from human mesenchymal stem cells for the recovery of sequelae of cerebral infarction.

Despite a dramatic increase in ischemic stroke incidence worldwide, effective therapies for attenuating sequelae of cerebral infarction are lacking. This study investigates the use of human mesenchymal stem cells (hMSCs) induced toward glia-like cells (ghMSCs) to ameliorate chronic sequelae resulting from cerebral infarction. Transcriptome analysis demonstrated that ghMSCs exhibited astrocytic characteristics, and assessments conducted ex vivo using organotypic brain slice cultures demonstrated that ghMSCs exhibited superior neuroregenerative and neuroprotective activity against ischemic damage compared to hMSCs. The observed beneficial effects of ghMSCs were diminished by pre-treatment with a CXCR2 antagonist, indicating a direct role for CXCR2 signaling. Studies conducted in rats subjected to cerebral infarction demonstrated that ghMSCs restored neurobehavioral functions and reduced chronic brain infarction in a dose-dependent manner when transplanted at the subacute-to-chronic phase. These beneficial impacts were also inhibited by a CXCR2 antagonist. Molecular analyses confirmed that increased neuroplasticity contributed to ghMSCs' neuroregenerative effects. These data indicate that ghMSCs hold promise for treating refractory sequelae resulting from cerebral infarction by enhancing neuroplasticity and identify CXCR2 signaling as an important mediator of ghMSCs' mechanism of action.

Association of Hemoglobin Decrement During Hospitalization with Prognosis of Aneurysmal Subarachnoid Hemorrhage and Mediation Effects of Cerebral Infarction and Pneumonia.

Hemoglobin decrement is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) and is associated with poor outcome. However, the mediating variables on the causal pathway between hemoglobin decrement and poor outcome in aSAH are not clear. This is a single-center retrospective observational study containing all consecutive patients with aSAH admitted to our hospital between January 1, 2019, and June 30, 2022. Hemoglobin decrement was defined as the hemoglobin at admission minus the minimum hemoglobin during hospitalization. Calculation of cutoff value using ROC curve Youden index. The main exposure of interest was a hemoglobin decrement greater than the cutoff value. The primary outcome was poor outcome at 3 months (mRS 4-6). A total of 480 patients with aSAH were included in the study, 414 (71.1%) had a favorable and 66 (28.9%) had a poor outcome at 3 months. The cut-off value for calculating the degree of hemoglobin decrease using the ROC curve was 12.5 g/l. Hemoglobin decrement greater than the cutoff value was significantly associated with pneumonia (OR 3.12; 95% CI 1.78-5.57; p < 0.001), cerebral infarction (OR 3.06; 95% CI 1.80-5.30; p < 0.001), and poor prognosis (OR 2.88; 95% CI 1.44-5.92; p = 0.003) at 3 months. The mediation effect was significant for both pneumonia and cerebral infarction, with the average causal mediation effect (ACME) were 0.04 (95% CI 0.02-0.08; p < 0.05) and 0.05 (95% CI 0.02-0.08; p < 0.001), respectively. Hemoglobin decrement during hospitalization was significantly associated with poor prognosis after aSAH, and the increased risk of cerebral infarction and pneumonia might mediate this effect. Avoiding hemoglobin decrement greater than 12.5g/l may improve the prognosis of patients with aSAH.

Factors associated with mortality and functional outcome after decompressive craniectomy in malignant middle cerebral artery infarction

ObjectiveIdentifying the predictive factors of mortality and functional outcomes following decompressive craniectomy (DC) surgery in patients with malignant middle cerebral artery infarction (MMCAI) is essential for decision-making regarding conservative versus surgical treatment. This study aimed to assess the mortality and functional outcomes of MMCAI patients after DC surgery and to identify the predictive factors associated with mortality and functional outcomes.MethodsA total of 76 patients with MMCAI who underwent surgical DC were included. The mortality rates and functional outcomes were assessed, and factors associated with mortality and functional outcomes were identified through univariate analysis followed by multivariate logistic regression analysis.ResultsThe mortality rate was 44.8%, while a favorable functional outcome was observed in 28.9% of the patients. modified Glasgow coma scale (GCS) before DC (OR = 0.416, 95% CI = 0.261–0.662, P < 0.001) and infarct volume before DC (OR = 1.000-1.012, 95% CI = 1.000-1.012, P = 0.037) were independent risk factors for death. Age (OR = 0.88, 95% CI = 0.812–0.952, P = 0.002), modified GCS before DC (OR = 2.477, 95% CI = 1.395-4.4, P = 0.002), and infarct volume before DC (OR = 0.987, 95% CI = 0.975–0.999, P = 0.035) were independent factors associated with favorable functional outcomes.ConclusionPreoperative modified GCS and preoperative infarct volume were independent factors associated with both mortality and functional outcomes. Age was only associated with functional outcomes.

The benefit of optimizing recanalization during mechanical thrombectomy in patients with acute ischemic stroke depends on preprocedural tissue-level collateralization.

Thrombolysis in Cerebral Infarction (TICI) 3 represents the optimal angiographic outcome following mechanical thrombectomy (MT) for acute ischemic stroke (AIS). Although it is known to yield better outcomes than TICI 2b, the influence of preprocedural cerebral hemodynamics on the clinical advantage of TICI 3 over TICI 2b remains unexplored. This single-center retrospective analysis involved patients with anterior circulation AIS who underwent successful recanalization during MT at the Comprehensive Stroke Center, University Hospital, Krakow between January 2019 and July 2023. We assessed the benefit of achieving TICI 2c/3 over TICI 2b on the basis of preprocedural computed perfusion imaging results, primarily focusing on early infarct volume (EIV) and tissue-level collaterals indicated by hypoperfusion intensity ratio (HIR). Good functional outcome (GFO) was defined as a modified Rankin Score < 3 on day 90. The study comprised 612 patients, of whom 467 (76.3%) achieved TICI 2c/3. GFO was more frequent in the TICI 2c/3 group (54.5% vs 69.4%, p < 0.001). There was interaction between the recanalization status and both HIR (Pi = 0.042) and EIV (Pi = 0.012) in predicting GFO, with disproportionately higher impact of HIR and EIV in TICI 2b group. The benefit from TICI 2c/3 over TICI 2b was insignificant among patients with good collaterals, defined by HIR < 0.3 (odds ratio:1.36 [0.58-3.18], p = 0.483). TICI 2c/3 improves patient functional outcomes compared to TICI 2b regardless of EIV. However, such angiographic improvement may be clinically futile in patients with good tissue-level collateralization. Our findings suggest that preprocedural HIR should be considered when optimization of recanalization is considered during MT.

Comparison of Hemorrhage on CT Versus MRI After Thrombectomy: The HECATE Study

Background The characterization of hemorrhage following acute stroke intervention has largely been computed tomography (CT) based. We sought to compare magnetic resonance imaging‐ (MRI‐) and CT‐based scoring of hemorrhage after acute endovascular therapy (EVT) applying the Heidelberg Bleeding Classification (HBC) to assess intermodal agreement and quantify interrater agreement. Methods Consecutive patients with acute stroke were included in this retrospective study if they (1) had MRI and CT ≤12 hours of each other OR (2) had CT bracketed by MRI pre‐ and post‐CT (ie, MRI‐CT‐MRI) ≤7 days post‐EVT. The concordance of the HBC ratings by consensus panel were compared between CT and T2 * gradient recalled echo MRI. Results For the 87 EVT‐treated patients included, median age was 68 years [60–74], admission National Institutes of Health Stroke Scale score 18 [13–23], 47% were treated with intravenous/intraarterial thrombolytics, and 93% were successfully recanalized (modified Thrombolysis in Cerebral Infarction 2b/3). Hemorrhage was detected on at least 1 modality in 60% (52/87) of patients. We found a 68% (59/87, 95% CI [57%–77%]) agreement overall between CT and MRI for hemorrhage classification post‐EVT. MRI had the best interrater agreement for HBC 0 (no hemorrhage) with excellent concordance (ĸ = 0.882), compared with CT (ĸ = 0.683). T2 * gradient recalled echo MRI tended to have increased sensitivity to scattered petechial hemorrhage (HBC 1a) as compared with CT with 17% (2/12) intermodal agreement. The interrater agreement of HBC class 2 (ie, parenchymal hematoma grade 2 was substantial for MRI (ĸ = 0.781) and excellent in CT (ĸ = 0.951), with 67% (8/12) intermodal agreement. Subarachnoid hemorrhage was detected in 24% (21/87) of patients on CT and/or MRI with 29% (6/21) intermodal agreement. Conclusion With the exception of subarachnoid hemorrhage and minor petechial hemorrhagic transformation, we found that MRI and CT are overall interchangeable for detecting and classifying hemorrhage after EVT. These findings are reassuring for both clinical decision‐making and research application. Given the complexity of hemorrhage subtypes post‐EVT, work to further refine a post‐EVT hemorrhage classification scale with clinical correlation would be beneficial.

Electroacupuncture Protects Against Cerebral Ischemia-Reperfusion Injury: Reducing Inflammatory Response and Cell Pyroptosis by Inhibiting P2X7/NLRP3/GSDMD Pathway.

To investigate the mechanism underlying the effects of Tongdu Tiaoshen electroacupuncture in the treatment of cerebral ischemia-reperfusion (I/R) injury. Sixty adult male Sprague-Dawley (SD) rats were randomly allocated to five groups (n=12): Sham, I/R, electroacupuncture (EA), BBG (P2X7R inhibitor), and MCC950 (NLRP3 inhibitor). The EA group received acupuncture at Shenting (GV24), Baihui (GV20), and Dazhui (GV14) points with a stimulation frequency of 2/5 Hz, intensity of 2 mA, and a duration of 40 min. Neurologic deficit scoring was then performed, and cerebral infarction volume was determined using triphenyl tetrazolium chloride (TTC) staining. Morphological changes in neurons in cortical areas were observed using an electron microscope, interleukin-18 (IL-18) and interleukin-1β (IL-1β) levels were assessed via the enzyme-linked immunosorbent assay (ELISA). Moreover, the expression of P2X7R/NLRP3/GSDMD pathway-related proteins and mRNAs was quantified by immunofluorescence staining, Western blot assay, and real-time fluorescence quantitative (RT-PCR) analysis. Electroacupuncture improved neurologic deficit scores, cerebral infarct size, and cell pyroptosis, and reduced IL-1β and IL-18 levels. Furthermore, electroacupuncture and inhibitor treatment significantly downregulated the expression of P2X7R, ASC, Caspase-1, NLRP3, and GSDMD involved in the P2X7/NLRP3/GSDMD signaling pathway. Tongdu Tiaoshen electroacupuncture may exert cerebral protection by inhibiting neuroinflammation through the P2X7/NLRP3/GSDMD pathway and reducing cellular pyroptosis.

Mechanisms of polygalasaponin F against brain ischemia-reperfusion injury by targeting NKCC1

Stroke is a serious threat to human health and current clinical therapies remain unsatisfactory. Elevated expression of Na+-K+-2Cl− cotransporter 1 (NKCC1) following stroke can disrupt the blood-brain barrier (BBB) and result in brain edema, indicating that NKCC1 may be a potential therapeutic target for improving stroke outcomes. Polygalasaponin F (PGSF) is a triterpenoid saponin isolated from Polygala japonica Houtt, which has showed neuroprotective effects in previous studies. The present study aimed to assess the protective effects of PGSF on cerebral ischemia-reperfusion injury (CIRI) in vivo and elucidate its underlying mechanism by targeting NKCC1. Experimental results revealed that following CIRI, rats displayed neurological deficits, cerebral infarction and brain edema, concurrent with increased NKCC1 mRNA and protein expression in the cerebral tissue. Notably, the administration of PGSF at both 10 mg/kg and 20 mg/kg effectively mitigated these adverse outcomes. To explore the mechanism of PGSF, pyrosequencing was used to find that CIRI reduces the methylation of the NKCC1 promoter, while PGSF enhances it. It was thereby demonstrated that PGSF could reduce NKCC1 expression in this manner. Simultaneously, we also observed that the protein expression of DNA methyltransferase 1 (DNMT1) in the ischemic penumbra was augmented after CIRI, whereas PGSF reduced the expression of DNMT1, which was contrary to the trend of NKCC1 methylation. These results imply that the enhancement of NKCC1 methylation by PGSF may not be catalyzed by DNMT1 and that the reduction of NKCC1 methylation level after CIRI may not be related to DNMT1. Finally, we discovered that PGSF can decrease the leakage of the BBB and enhance the expression of the BBB structural proteins occludin and ZO-1. In conclusion, PGSF can target NKCC1 as an epigenetic target and downregulate its expression following CIRI by enhancing DNA methylation of NKCC1, thereby safeguarding the structure and function of brain tissue.

Buyang Huanwu Decoction restores the balance of mitochondrial dynamics after cerebral ischemia-reperfusion through calcium overload reduction by the PKCε-Nampt-Sirt5 axis

Ethnopharmacological relevanceStroke is a common condition that poses a significant threat to human health. Buyang Huanwu Decoction (BYHWD) is a traditional treatment used for stroke management. However, the exact mechanism by which BYHWD mitigates cerebral ischemia-reperfusion by regulating calcium overload and restoring mitochondrial function is not yet fully understood. AimThe objective of this research was to examine the neuroprotective properties of BYHWD in reducing the damage produced by cerebral ischemia/reperfusion (I/R) injury via the modulation of calcium overload and mitochondrial dynamics (MD). MethodsMCAO/R model success was evaluated via PSI laser scatter flowmetry. The neurological function scores were assessed. The cerebral infarct (CI) volume was detected via TTC staining. NeuN expression was detected via immunohistochemistry, and degenerated neurons were observed via FJC staining. The mitochondrial permeability transition pore (mPTP), the mitochondrial membrane potential (MMP), and ATP were detected. The reactive oxygen species (ROS) content and the NAD+/NADH ratio were determined. The glutamate (Glu) and glutamine (Gln) contents as well as the Ca2+ concentration were determined. The expression of PKCε, p-PKCε, namely, Sirt5, GLS, Drp1, p-Drp1 616, Fis1, Opa1, and Mfn2 was determined via Western blotting. Immunohistochemistry was used to detect p-PKCε, which is expressed at high levels. Immunofluorescence was used to detect p-Drp1 616, Opa1 and Sirt5 fluorescence intensity. ResultsBYHWD treatment enhanced neurological function, decreased the amount of CI, mitigated neuronal damage, decreased mPTP opening, restored the MMP, increased ATP synthesis, and decreased the ROS content after brain I/R. It also increased PKCε, p-PKCε, Sirt5, GLS, Opa1 and Mfn2 expression; downregulated p-Drp1 616, Drp1 and Fis1 expression; elevated the NAD+/NADH ratio and Gln content; and decreased the Glu content and Ca2+ concentration. The effects of BYHWD were reversed by the administration of the PKCε inhibitor εV1-2. BYHWD administration led to increased PKCε mRNA expression. ConclusionsBYHWD modulates MD by diminishing calcium overload through the PKCε-Nampt-Sirt5 axis, which restores mitochondrial function and mitigates brain I/R damage.

Clinical Observation of Infarct Volume ≥150mL in Endovascular Thrombectomy Treatment.

Whether patients with infarct volume ≥150mL could benefit from endovascular thrombectomy (EVT) remains unclear. Patients (n=104) with anterior circulation Alberta Stroke Program Early Computed Tomography Score <6 were screened for infarct volume ≥150mL using the Pullicino formula × (1-22%). The following were compared with the baseline at 90 days: the modified Rankin scale score (mRS) ≤3, mortality rate, symptomatic intracranial hemorrhage and any intracranial hemorrhage within 48 hours, and modified Thrombolysis in Cerebral Infarction (mTICI) ≥2b between the EVT and drug therapy (DT) groups. In patients with infarct volumes ≥150mL, mRS≤3 at 90 days was higher in the EVT group than in the DT group [adjusted odds risk (aOR), 5.52; 95% CI: 1.10-28.24, P =0.04), and mTICI ≥2b at 82.8%. Intracranial hemorrhage within 48 hours occurred in 7 (24.1%) patients in the EVT group and 5 (14.7%) in the DT group (aOR, 0.75; 95% CI: 0.16-3.46; P =0.71). Older age (aOR, 0.94; 95% CI: 0.90-0.99, P =0.01), EVT treatment (aOR, 4.51; 95% CI: 1.60-12.78, P =0.01), and infarct volume ≥150mL (aOR, 0.11; 95% CI: 0.04-0.31, P <0.01) were significantly associated with patient prognosis. Patients with infarct volume ≥150mL who received EVT had a higher proportion of mRS≤3 compared with those who received DT. However, there was no statistically significant difference in intracranial hemorrhage and death between the groups. EVT, smaller infarct volume, and younger age were associated with a good prognosis. The findings require large sample data verification.

Toward Automated Detection of Microbleeds with Anatomical Scale Localization Using Deep Learning

Cerebral Microbleeds (CMBs) are chronic deposits of small blood products in the brain tissues, which have explicit relation to various cerebrovascular diseases depending on their anatomical location, including cognitive decline, intracerebral hemorrhage, and cerebral infarction. However, manual detection of CMBs is a time consuming and error-prone process because of their sparse and tiny structural properties. The detection of CMBs is commonly affected by the presence of many CMB mimics that cause a high false-positive rate (FPR), such as calcifications and pial vessels. This paper proposes a novel 3D deep learning framework that not only detects CMBs but also identifies their anatomical location in the brain (i.e., lobar, deep, and infratentorial regions). For the CMBs detection task, we propose a single end-to-end model by leveraging the 3D U-Net as a backbone with Region Proposal Network (RPN). To significantly reduce the false positives within the same single model, we develop a new scheme, containing Feature Fusion Module (FFM) that detects small candidates utilizing contextual information and Hard Sample Prototype Learning (HSPL) that mines CMB mimics and generates additional loss term called concentration loss using Convolutional Prototype Learning (CPL). For the anatomical localization task, we exploit the 3D U-Net segmentation network to segment anatomical structures of the brain. This task not only identifies to which region the CMBs belong but also eliminates some false positives from the detection task by leveraging anatomical information. We utilize Susceptibility-Weighted Imaging (SWI) and phase images as 3D input to efficiently capture 3D information. The results show that the proposed RPN that utilizes the FFM and HSPL outperforms the baseline RPN and achieves a sensitivity of 94.66% vs. 93.33% and an average number of false positives per subject (FPavg) of 0.86 vs. 14.73. Furthermore, the anatomical localization task enhances the detection performance by reducing the FPavg to 0.56 while maintaining the sensitivity of 94.66%.

Anisodine hydrobromide injection promotes neural remodeling and recovery after ischemic stroke in mice.

Anisodine hydrobromide injection has shown promising therapeutic effects in treating patients with cerebral infarction, improving recovery of neurological function during the post-cerebral infarction period. However, the effects of anisodine hydrobromide on brain recovery and neuroplasticity are unclear. This study explores the therapeutic effects and underlying mechanisms of anisodine hydrobromide in mice experiencing the chronic phase of an ischemia stroke. The electrocautery method established a distal middle cerebral artery occlusion (MCAO) model in healthy male C57BL/6 mice. Neurological deficits were evaluated using Golgi and immunofluorescence staining to measure the effects of anisodine hydrobromide on neural proliferation, migration and remodeling. DAPT (dipeptidic γ-secretase-specific inhibitor) was employed to explore the involvement of the Notch signaling pathway post-anisodine hydrobromide treatment. Compared to the control and MCAO groups, mice treated with anisodine hydrobromide showed improved post-stroke neurological function, increased neurite intersections, and dendritic spine density in the peri-infarct cortex. Anisodine hydrobromide also promoted neural cell regeneration which is dendritic and axonal structures and synaptic vesicle protein restructuring. Gap43, NGF, Notch1, and Hes1 protein level increased significantly in the ANI group provided inhibitor DAPT was absent. Anisodine hydrobromide can promote neurological function, neurotrophic factors, and neuroplasticity. Notch signaling pathways also impact the effects of anisodine hydrobromide on neural plasticity in ischemia stroke.

Long-term FXa inhibition attenuates thromboinflammation after acute myocardial infarction and stroke by platelet proteome alteration

BackgroundImmediate activated factor (F)X (FXa) inhibition exerts direct antiplatelet effects in the context of arterial thrombosis but little is known about the impact of long-term therapy on platelet function in ischemic cardiovascular diseases. ObjectivesTherefore, we analyzed platelet-derived effects of long-term FXa inhibition in the setting of acute myocardial infarction (AMI) and stroke. MethodsWe evaluated the effect of acute versus chronic FXa inhibition on thromboinflammation following AMI and stroke in mice in vivo. Mechanistically, we identified changes in platelet gene expression and proteome under chronic FXa nonvitamin K antagonist oral anticoagulant treatment and characterized its functional consequence on platelet physiology. In a prospectively recruited cohort of patients with AMI, we determined cardiovascular magnetic resonance based cardiac endpoints under FXa nonvitamin K antagonist oral anticoagulant effects on clinical endpoints in a cohort of patients with AMI. ResultsChronic but not acute FXa inhibition reduced cerebral and myocardial infarct size and improved cardiac function 24 hours after AMI in mice. Mechanistically, we identified an attenuated thromboinflammatory response with reduced neutrophil extracellular trap formation in mice and patient samples. Proteome and RNA expression analysis of FXa inhibitor treated patients revealed a reduction of key regulators within the membrane trafficking and secretion machinery hampering platelet α and dense granule release. Subsequent, thromboinflammatory neutrophil extracellular trap density in thrombi isolated from stroke and myocardial infarction patients was reduced. Patients with AMI treated with FXa inhibitors showed decreased infarct size after myocardial infarction compared to patients without anticoagulation treatment. ConclusionLong-term FXa inhibition induces antithromboinflammatory proteome signatures in platelets, improving infarct size after myocardial infarction and stroke.

Lifestyle-Related Diseases and Stroke

Lifestyle-related diseases are also associated with stroke incidence. Among these, hypertension, diabetes mellitus, dyslipidemia, obesity, and metabolic syndrome have significant impacts on stroke. Hypertension is the greatest risk factor for stroke among lifestyle-related diseases. Among the medical treatments for lifestyle-related diseases, antihypertensive management is the most important. Recently, due to lifestyle changes such as westernization of diet and lack of exercise, the incidence of diabetes mellitus, dyslipidemia, obesity, and metabolic syndrome has been increasing. They significantly affect atherothrombotic cerebral and lacunar infarctions. However, a few patients with lifestyle-related diseases remain untreated. Therefore, the early diagnosis and treatment of lifestyle-related diseases are extremely important to reduce the risk of stroke. Smoking and heavy alcohol consumption are risk factors for stroke. Guidelines for lifestyle factors are important for stroke prevention.

Docosahexaenoic acid protects against ischemic stroke in diabetic mice by inhibiting inflammatory responses and apoptosis

This study was to explore whether docosahexaenoic acid (DHA) protects against ischemic stroke in diabetic mice and its mechanisms. DHA was administered to mice and its effects on stroke outcomes in type 1 diabetes mellitus were assessed 24 h and 3 days post-reperfusion using RNA sequencing, flow cytometry, multiplex immunoassays, and western-blotting analysis. In diabetic mice, DHA administration post-ischemic stroke significantly reduced cerebral infarct size, brain edema, and neurological impairments. Flow cytometric analysis demonstrated a notable decrease in the percentage of neutrophils in the ischemic brain, suggesting a mitigated inflammatory response. Western blotting assay revealed that pro-apoptotic protein Bax was reduced whereas anti-apoptotic protein Bcl-2 was increased, indicating the attenuation of apoptosis. Additionally, RNA sequencing of brain tissue highlighted significant transcriptomic changes, with downregulation of genes for several inflammatory pathways such as NF-kappa B signaling and upregulation of genes for neuroprotective pathways such as neuroactive ligand-receptor interaction. Similar transcriptomic changes in peripheral blood mononuclear cells indicated that DHA treatment resulted the systemic anti-inflammatory and neuroprotective response. DHA treatment mitigated cerebral ischemic injuries by dampening inflammatory responses and apoptosis in diabetic mice after ischemic stroke, highlighting its therapeutic potential for clinical management of stroke in diabetic patients.

Visualizing Intraoperative Transcranial Motor-Evoked Potentials During Glioma Surgery for Predicting Postoperative Paralysis Prognosis

The primary goals of glioma surgery are maximal tumor resection and preservation of brain function. Intraoperative motor-evoked potential (MEP) monitoring is commonly used to predict and minimize postoperative paralysis. However, studies on intraoperative MEP trends and postoperative paralysis are scarce. This study aimed to determine the relationship between intraoperative MEP trends and postoperative paralysis. This retrospective study evaluated 229 patients with supratentorial glioma without preoperative paralysis who underwent tumor resection surgery under general anesthesia at our institution between October 2019 and December 2022. Intraoperative transcranial MEP monitoring was performed, and the entire MEP trends on affected and unaffected sides was visualized. Postoperative paralysis and patient-related factors were analyzed. Postoperative paralysis occurred in 36 patients, with the paralysis improving over time and being permanent in 30 and 6 patients, respectively. In the improvement group, the temporary decrease in transcranial MEP rapidly improved. Even when the MEPs were <50% of the control value, fluctuations indicating improvement were observed after the decrease. However, in the permanent paralysis group, transcranial MEP remained consistently <50% of the control value until the end of surgery, after its initial decrease. The significant factors contributing to permanent paralysis were tumor localization close to the pyramidal tract (p = 0.0304) and postoperative cerebral infarction in the pyramidal tract (p = 0.0009). The overall intraoperative MEP trend can reflect the risk of postoperative paralysis during glioma surgery. Thus, visualizing this trend can provide a better understanding of the prognosis of postoperative paralysis.

Age-Related Differences in Clinical Characteristics and Outcomes of Aneurysmal Subarachnoid Hemorrhage: A Retrospective Study of 657 Patients

Aneurysmal subarachnoid hemorrhage (aSAH) has an incidence of 6-7 per 100,000 person-years. Despite advancements in treatment, 26% of patients die, and 19% remain dependent post-hemorrhage. Long-term neuropsychological sequelae affect about half of the survivors, significantly impacting their quality of life. This study aims to assess aSAH characteristics and identify predictive factors of clinical outcomes in young patients. A retrospective study analyzed 657 aSAH patients treated at two South Korean medical centers from January 2011 to December 2023. Data on demographics, comorbidities, smoking history, clinical grades, aneurysm size and location, and outcomes were collected. Outcomes were classified using the modified Rankin Scale (mRS), with scores ≤2 indicating good outcomes. The cohort included 233 men and 424 women (male-to-female ratio 1:1.8). Most patients were middle-aged (74.4%), followed by young (16.7%) and old (8.8%) groups. Young patients exhibited male predominance (56.8%), lower hypertension (12.7%) and diabetes (1.8%) rates, and higher smoking rates (39.6%). Older patients had higher hypertension (44.6%) and diabetes (23.3%) rates, and were predominantly female (69.1%). Aneurysms in young patients were smaller (p=0.04). Multivariate analysis identified poor Hunt-Hess grade, permanent cerebral infarction, and aneurysmal recurrence or rebleeding as predictors of poor outcomes in young patients. Middle-aged patients had additional predictors, including diabetes and hydrocephalus. In older patients, only poor Hunt-Hess grade was significant. Young aSAH patients exhibit distinct characteristics and prognostic factors compared to older patients. Despite higher post-operative complications, young patients generally have better outcomes, emphasizing the need for age-specific management strategies in aSAH.

Protopine Exerts Neuroprotective Effects on Neonatal Hypoxic-Ischemic Brain Damage in Rats via Activation of the AMPK/PGC1α Pathway.

Neonatal hypoxic-ischemic encephalopathy (HIE), caused by perinatal asphyxia, is characterized by high morbidity and mortality, but there are still no effective therapeutic drugs. Mitochondrial biogenesis and apoptosis play key roles in the pathogenesis of HIE. Protopine (Pro), an isoquinoline alkaloid, has anti-apoptotic and neuro-protective effects. However, the protective roles of Pro on neonatal hypoxic-ischemic brain injury remain unclear. In this study, we established a CoCl2-induced PC12 cell model in vitro and a neonatal rat hypoxic-ischemic (HI) brain damage model in vivo to explore the neuro-protective effects of Pro and try to elucidate the potential mechanisms. Our results showed that Pro significantly reduced cerebral infarct volume, alleviated brain edema, inhibited glia activation, improved mitochondrial biogenesis, relieved neuron cell loss, decreased cell apoptosis and reactive oxygen species (ROS) after HI damage. In addition, Pro intervention upregulated the levels of p-AMPK/AMPK and PGC1α as well as the downstream mitochondrial biogenesis related factors, such as nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM), but the AMPK inhibitor compound c (CC) could significantly reverse these effects of Pro. Pro may exert neuroprotective effects on neonatal hypoxic-ischemic brain damage via activation of the AMPK/PGC1α pathway, suggesting that Pro may be a promising therapeutic candidate for HIE, and our study firstly demonstrate the neuro-protective roles of Pro in HIE models.

The First Case of Cerebral Infarction Associated with Essential Thrombocythemia and MPL Mutation in South Korea

The First Case of Cerebral Infarction Associated with Essential Thrombocythemia and MPL Mutation in South Korea

Mechanical Thrombectomy for Treatment of Acute Cerebral Infarction due to Distal Medium Vessel Occlusions: A Retrospective Cohort Study.

Mechanical thrombectomy (MT) is standard of care for acute cerebral infarction (ACI) due to large vessel occlusions. However, its clinical efficacy in patients with ACI due to distal medium vessel occlusions (DMVOs) remains unclear. This study evaluates the efficacy and safety of MT in patients with ACI due to DMVOs. Totally, 306 patients with ACI at a very early stage were assigned into DMVOs-MT, M1-MT, and DMVOs-intravenous thrombolysis (IVT) groups. These groups were compared regarding baseline data, recanalization rate, location of vessel occlusions, number of thrombectomy, first-pass recanalization, mRS scores, NIHSS scores, 90-day mRS scores, incidence of adverse events, and mortality. Risk factors for poor prognosis of patients with DMVOs following MT were analyzed. DMVOs-MT and M1-MT groups showed comparable first-pass recanalization rates, recanalization rates, and NIHSS score reduction ratios, with marked differences in location of vessel occlusions. Versus DMVOs-IVT, DMVOs-MT had increased differences between pre- and post-treatment NIHSS scores and between pre-treatment NIHSS scores and NIHSS scores at discharge and elevated NIHSS reduction ratios. The poor prognosis rate of DMVOs-MT group was insignificantly different from that of M1-MT group but lower than that of DMVOs-IVT group. Adverse events and mortality incidences were comparable among the three groups. Diabetes, first-pass recanalization, and pre-treatment NIHSS scores were independent risk factors for poor prognosis in DMVO patients after MT. MT is as effective and safe in patients with DMVOs as in patients with M1 occlusions. In patients with DMVOs, MT has higher efficacy and safety than IVT.

Intra-arterial alteplase for acute ischaemic stroke after mechanical thrombectomy (PEARL): rationale and design of a multicentre, prospective, open-label, blinded-endpoint, randomised controlled trial.

Successful reperfusion does not always lead to good neurological outcomes and impaired microcirculation can be one of the underlying causes. Intra-arterial alteplase after mechanical thrombectomy (MT) may improve microcirculation contributing to neurological recovery, but prospective randomised studies are still needed to validate its efficacy and safety. We aim to assess the efficacy and safety of intra-arterial alteplase after MT for acute ischaemic stroke (AIS) with large-vessel occlusion (LVO). The Intra-arterial Alteplase for Acute Ischaemic Stroke After Mechanical Thrombectomy (PEARL) study is a multicentre, prospective, open-label, blinded-endpoint, randomised controlled trial. We consecutively screen AIS patients with anterior circulation LVO and National Institute of Health Stroke Scale of 6-25, who reach stable expanded Thrombolysis in Cerebral Infarction scores of 2b50-3 on angiography after MT. Eligible participants are 1:1 randomly assigned to the experimental group and the control group. Participants in the experimental group will receive intra-arterial alteplase (0.225 mg/kg and a maximum dose of 20 mg) after MT and standard medical treatment, while those in the control group will receive standard medical treatment alone after the procedure. The primary outcome is the proportion of patients with a 90-day modified Rankin scale of 0-1. A total of 324 participants are required to test the superiority hypothesis with 80% power at a two-tailed significance level of 0.05. This study has been approved by the Ethics Committee of Sun Yat-sen Memorial Hospital, Sun Yat-sen University (SYSKY-2023-390-02) and will be conducted following the Declaration of Helsinki. Ethical approvals have been obtained separately for all centres participating in the study. Study results will be published in peer-reviewed academic journals. NCT05856851.