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Ischemic stroke caused by cerebral artery occlusion induces neurological deficits because of cell damage or death in the central nervous system. Given the recent therapeutic advances in reperfusion therapies, some patients can now recover from an ischemic stroke with no sequelae. Currently, reperfusion therapies focus on rescuing neural lineage cells that survive in spite of decreases in cerebral blood flow. However, vascular lineage cells are known to be more resistant to ischemia/hypoxia than neural lineage cells. This indicates that ischemic areas of the brain experience neural cell death but without vascular cell death. Emerging evidence suggests that if a vascular cell-mediated healing system is present within ischemic areas following reperfusion, the therapeutic time window can be extended for patients with stroke. In this review, we present our comments on this subject based upon recent findings from lethal ischemia following reperfusion in a mouse model of stroke.

Background Intracerebral hemorrhage (ICH) is a significant cause of death and disabilities. Recently, cell therapies using mesenchymal stem cells have been shown to improve ICH-induced neurobehavioral deficits. Based on these findings, we designed this study to evaluate the therapeutic efficacy and underlying mechanisms by which human amnion-derived stem cells (hAMSCs) would ameliorate neurobehavioral deficits of ICH-bearing hosts. Methods hAMSCs were induced from amnia obtained by cesarean section and administered intravenously to ICH-bearing mice during the acute phase. The mice were then subject to multitask neurobehavioral tests at the subacute phase. We attempted to optimize the dosage and timing of the hAMSC administrations. In parallel with the hAMSCs, a tenfold higher dose of human adipose-derived stem cells (ADSCs) were used as an experimental control. Specimens were obtained from the ICH lesions to conduct immunostaining, flow cytometry, and Western blotting to elucidate the underlying mechanisms of the hAMSC treatment. Results The intravenous administration of hAMSCs to the ICH-bearing mice effectively improved their neurobehavioral deficits, particularly when the treatment was initiated at Day 1 after the ICH induction. Of note, the hAMSCs promoted clinical efficacy equivalent to or better than that of hADSCs at 1/10 the cell number. The systemically administered hAMSCs were found in the ICH lesions along with the local accumulation of macrophages/microglia. In detail, the hAMSC treatment decreased the number of CD11b + CD45 + and Ly6G + cells in the ICH lesions, while splenocytes were not affected. Moreover, the hAMSC treatment decreased the number of apoptotic cells in the ICH lesions. These results were associated with suppression of the protein expression levels of macrophage-related factors iNOS and TNFα. Conclusions Intravenous hAMSC administration during the acute phase would improve ICH-induced neurobehavioral disorders. The underlying mechanism was suggested to be the suppression of subacute inflammation and apoptosis by suppressing macrophage/microglia cell numbers and macrophage functions (such as TNFα and iNOS). From a clinical point of view, hAMSC-based treatment may be a novel strategy for the treatment of ICH.

In conjunction with recent advancements in machine learning (ML), such technologies have been applied in various fields owing to their high predictive performance. We tried to develop prehospital stroke scale with ML. We conducted multi-center retrospective and prospective cohort study. The training cohort had eight centers in Japan from June 2015 to March 2018, and the test cohort had 13 centers from April 2019 to March 2020. We use the three different ML algorithms (logistic regression, random forests, XGBoost) to develop models. Main outcomes were large vessel occlusion (LVO), intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH), and cerebral infarction (CI) other than LVO. The predictive abilities were validated in the test cohort with accuracy, positive predictive value, sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and F score. The training cohort included 3178 patients with 337 LVO, 487 ICH, 131 SAH, and 676 CI cases, and the test cohort included 3127 patients with 183 LVO, 372 ICH, 90 SAH, and 577 CI cases. The overall accuracies were 0.65, and the positive predictive values, sensitivities, specificities, AUCs, and F scores were stable in the test cohort. The classification abilities were also fair for all ML models. The AUCs for LVO of logistic regression, random forests, and XGBoost were 0.89, 0.89, and 0.88, respectively, in the test cohort, and these values were higher than the previously reported prediction models for LVO. The ML models developed to predict the probability and types of stroke at the prehospital stage had superior predictive abilities.

BackgroundDual antiplatelet therapy (DAPT) is necessary to prevent thromboembolic complications after stent-assisted coiling (SAC) or flow-diversion (FD) for cerebral aneurysms, but the optimal antiplatelet regimen remains unclear.ObjectiveTo determine the optimal DAPT duration in patients with SAC/FD.MethodsThis multicenter cohort study enrolled patients who received SAC/FD for cerebral aneurysms at seven Japanese institutions between January 2010 and December 2020. The primary outcome was the time from procedure to the occurrence of a composite of target vessel-related thromboembolic events, procedure-unrelated major bleeding events, or death. The cumulative event-free survival rates were analyzed using a Kaplan–Meier curve, and the differences in each outcome between the groups dichotomized by the duration of DAPT were analyzed using the log-rank test.ResultsOf 632 patients (median observational period, 646 days), primary outcome occurred in 63 patients (10.0%), most frequently within 30 days after the procedure. The cumulative event-free survival rates at 30 days, 1 year, and 2 years after the procedure were 93.3% (91.4 to 95.3%), 91.5% (89.3 to 93.7%), and 89.5% (87.0 to 92.0%), respectively. The cumulative event-free survival rates after switching to monotherapy were similar for the >91 and <90 days DAPT groups in the population limited to patients who were switched from DAPT to monotherapy without major clinical events.ConclusionsThromboembolic events rarely occurred beyond 30 days after SAC/FD. The duration of DAPT may be shortened if patients have a periprocedural period without events. Further prospective studies are warranted to determine the optimal duration of antiplatelet therapy.Trial registration numberUMIN000044122 :https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000050384.

Neuro-inflammation plays a key role in the pathophysiology of brain infarction. Cell therapy offers a novel therapeutic option due to its effect on immunomodulatory effects. Amniotic stem cells, in particular, show promise owing to their low immunogenicity, tumorigenicity, and easy availability from amniotic membranes discarded following birth. We have successfully isolated and expanded human amniotic mesenchymal stem cells (hAMSCs). Herein, we evaluated the therapeutic effect of hAMSCs on neurological deficits after brain infarction as well as their immunomodulatory effects in a mouse model in order to understand their mechanisms of action. One day after permanent occlusion of the middle cerebral artery (MCAO), hAMSCs were intravenously administered. RT-qPCR for TNFα, iNOS, MMP2, and MMP9, immunofluorescence staining for iNOS and CD11b/c, and a TUNEL assay were performed 8 days following MCAO. An Evans Blue assay and behavioral tests were performed 2 days and several months following MCAO, respectively. The results suggest that the neurological deficits caused by cerebral infarction are improved in dose-dependent manner by the administration of hAMSCs. The mechanism appears to be through a reduction in disruption of the blood brain barrier and apoptosis in the peri-infarct region through the suppression of pro-inflammatory cytokines and the M2-to-M1 phenotype shift.

We report the case of a woman in her fourth decade of life with a known nickel allergy. She visited the previous clinic complaining of a headache. Head MRI was performed, which showed a right internal carotid artery aneurysm, and she was referred to our hospital for further treatment. We planned treatment using coiling embolization with a balloon catheter because we were afraid of allergic reactions against the nickel device. However, recused stenting was done during the procedure to prevent coil migration. After the treatment, there were no post-procedure neurological complications or hypersensitivity reactions due to nickel allergy. No medication was given to suppress the hypersensitivity reaction. The patient was discharged from the hospital with no complications. This case demonstrates that nickel-containing stents can be safely used in selected patients with confirmed nickel allergy.

Background Meige syndrome is a segmental dystonia affecting the head and neck, with bilateral blepharospasm as the primary symptom. First-line treatment typically involves Botox injections. For cases resistant to this treatment, bilateral deep brain stimulation of the globus pallidus internus (GPi) is considered. This study explores the efficacy of unilateral radiofrequency (RF) lesioning as an alternative surgical treatment for Meige syndrome. Methods We investigated six cases of medically refractory Meige syndrome treated with unilateral RF lesioning between October 2022 and August 2023. The procedures utilized the Leksell Stereotactic System (Elekta, Stockholm, Sweden) and the StealthStation S8 system (Medtronic, Dublin, Ireland). Target coordinates were initially set at 8-9 mm lateral and 1-2 mm inferior to the mid-commissure point (MCP) for the pallidothalamic tract (PTT), and 20 mm lateral, 2 mm anterior, and 3.0-4.5 mm inferior to the MCP for GPi, with fine adjustments based on MRI findings. Results The mean age of patients was 53. 3 ±16.5 years. Five patients underwent PTT RF lesioning, while one received GPi RF lesioning (pallidotomy). No surgical complications were reported. The Burke-Fahn-Marsden Dystonia Rating Scale scores were 32.9 ± 19.4 preoperatively and 17.7 ± 13.9 three months postoperatively, reflecting an average improvement of 42.7%. The Jankovic Rating Scale scores were 7.17 ± 0.76 preoperatively, 2.33 ± 2.34 the day after surgery (average improvement of 67%), and 3.50 ± 1.64 three months postoperatively (average improvement of 51%). Bilateral facial symptoms improved in four patients (67%). Conclusion Unilateral RF lesioning for Meige syndrome demonstrated the potential to improve bilateral symptoms and may be considered a viable treatment option for patients with refractory cases.

Our previous study demonstrated that coagulation factor Xa (FXa) induced endothelial cell senescence, resulting in inflammation and impaired angiogenesis. This mechanism is dictated through protease-activated receptors, PARs, insulin-like growth factor-binding protein 5 (IGFBP-5), and p53. Activation of PARs contributes to the pathophysiology of several chronic inflammatory diseases, including atherosclerosis. Thus, we speculated that similar mechanism might participate in the progression of atherosclerotic plaques. In the present study, we successfully identified the cells that produced FX/Xa in atherosclerosis using human atherosclerotic plaques obtained from carotid endarterectomy. In situ hybridization for FX revealed that FX was generated in vascular smooth muscle cells (VSMC), inflammatory cells, and endothelial cells. Then, we examined the effects of FXa on the growth of VSMC in vitro . The present study revealed that chronic FXa stimulation significantly induced the senescence of VSMC with concomitant upregulation of IGFBP-5 and p53. Inhibition of FXa signaling with rivaroxaban or knock down of IGFBP-5 significantly reduced FXa-induced VSMC senescence and inflammatory cytokine production. Finally, we confirmed that FXa and IGFBP-5 are co-distributed in atherosclerotic plaques. In conclusion, induction of senescence of VSMC induced by locally produced FX/Xa may contribute to the progression of atherosclerosis.

We report a case with paretic focal hand dystonia, which at first glance was diagnosed as writer's cramp, with poor performance only when playing the guitar and writing but with increased muscle tension around the elbow rather than in the fingers and hands. The muscle tension was around the elbow and the pallidothalamic tract (PTT) was selected as the proximal muscle target with less permanent complications. During the operation, the PTT test electrical stimulation was impaired only for guitar playing, but not for other hand movements. Therefore, test lesioning at a lower temperature and for a shorter time improved the symptoms, so we were convinced that this was the target site and coagulated this site, i.e., the PPT, at the usual temperature and time. With only one target lesioning, the patient's symptoms disappeared for six months. Careful history taking and physical examination to identify the site of muscle tension is important in determining the target of paretic form dystonia. In addition, test lesioning at a lower temperature and for a shorter time is useful if the test electrical stimulation produces a paradoxically unexpected response.

This case report describes the use of pharmacologic vasodilation with intra-arterial isosorbide dinitrate to facilitate endovascular treatment of a foramen magnum dural arteriovenous fistula in a man in his 40s. The fistula was supplied by the posterior meningeal artery arising from the right vertebral artery and the hypoglossal branch of the ascending pharyngeal artery (APA). Catheterization of the APA was challenging due to its tortuous course and small caliber. To address this, 2 mg of isosorbide dinitrate was administered intra-arterially, resulting in effective vasodilation and allowing smooth microcatheter navigation. Embolization was then successfully performed using 12.5% n-butyl-2-cyanoacrylate, leading to a significant reduction in shunt flow. Follow-up angiography at three months confirmed complete obliteration of the fistula, and the patient remained neurologically intact, with no perioperative or delayed complications. This case highlights the potential utility of intra-arterial vasodilators, such as isosorbide dinitrate, in overcoming anatomical challenges during transarterial embolization and suggests their broader applicability in complex neuroendovascular procedures.