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Objective: The role of gamma‐aminobutyric acid‐ergic (GABAergic) neuron impairment in Alzheimer's disease (AD), and if and how transplantation of healthy GABAergic neurons can improve AD, remain unknown. Methods: Human‐derived medial ganglionic eminence progenitors (hiMGEs) differentiated from programmed induced neural precursor cells (hiNPCs) were injected into the dentate gyrus region of the hippocampus (HIP). Results: We showed that grafts migrate to the whole brain and form functional synaptic connections in amyloid precursor protein gene/ presenilin‐1 (APP/PS1) chimeric mice. Following transplantation of hiMGEs, behavioral deficits and AD‐related pathology were alleviated and defective neurons were repaired. Notably, exosomes secreted from hiMGEs, which are rich in anti‐inflammatory miRNA, inhibited astrocyte activation invitro and in vivo, and the mechanism was related to regulation of CD4+ Th1 cells mediated tumor necrosis factor (TNF) pathway. Interpretation: Taken together, these findings support the hypothesis that hiMGEs transplantation is an alternative treatment for neuronal loss in AD and demonstrate that exosomes with anti‐inflammatory activity derived from hiMGEs are important factors for graft survival. ANN NEUROL 2024;96:488–507 [ABSTRACT FROM AUTHOR]

Rosai-Dorfman disease (RDD) is a condition of unknown etiology, and characterized by the proliferation of histiocytes. RDD most commonly affects lymph nodes, and central nervous system (CNS) involvement is rare. Here, we describe the case of a 43-year-old man who presented with an intradural tumour of the thoracic spine. The patient underwent a laminectomy for tumour resection and pathology results diagnosed the tumour as a RDD. Two years later, brain magnetic resonance imaging (MRI) revealed multiple intracranial dural-based lesions. Prednisolone treatment was initiated and led to resolution of the disease. We reviewed the literature to the investigate clinical characteristics, imaging features, diagnosis and treatment protocols pertaining to such cases. [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate the impact of antiplatelet agents for stent-assisted coiling, including intravenous (IV) tirofiban as an antiplatelet premedication, on rates of external ventricular drain (EVD)-related hemorrhage in acutely ruptured intracranial aneurysms. The impact of IV tirofiban in particular was also evaluated. Rates of radiographically identified hemorrhage associated with EVD placement were compared between patients who received an antiplatelet agent for stent-assisted coil embolization (SACE), and patients who did not receive an antiplatelet agent between June 2013 and June 2019. 78 patients treated for a ruptured aneurysm which required an EVD were included. A total of 46 patients who underwent stent-assisted coiling and received IV tirofiban and oral asipirin and clopidogrel (DAPT) were included in the antiplatelet group, while 32 who underwent single coiling and received no antiplatelet therapy were included in the control group. Overall, EVD-related hemorrhage occurred in 13 patients (16.67%): 11 (23.91%) in the antiplatelet group and 2 (6.25%) in the control group (p = 0.040). Of 37 patients who underwent computed tomography after SACE, but before the use of DAPT, 8 (21.62%) exhibited EVD-related hemorrhage after IV tirofiban therapy (p = 0.070 vs. control group). EVD-related hemorrhage was not significantly different between patients with EVD placement after coil embolization versus before coil embolization (p = 0.124). In the subgroup analysis for the antiplatelet group, we did not observed increased EVD-related hemorrhage in patients receiving EVD placement after administration of antiplatelet agents (8/27 [29.63%]) versus before administration of antiplatelet agents (3/19 [15.79%]). Patients with ruptured aneurysm who receive an antiplatelet agent for stent-assisted coiling are at a higher risk for EVD-related hemorrhage. The order of EVD placement and EVT, as well as the order of EVD placement and antiplatelet initiation do not appear to be significantly different regarding the outcome of EVD-related hemorrhage. Patients with ruptured aneurysm who receive an antiplatelet agent for stent-assisted coiling are at a higher risk for EVD-related hemorrhage. There was a trend towards higher EVD related haemorrhage when tirofiban was used but it did not reach statisitical significance. The order of EVD—whether before vs after endovascular treatment, or before vs after antiplatelet therapy did not influence the EVD-related hemorrhage rates. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies have shown that oligodendrocytes and motor neurons have the same progenitors in the ventral spinal cord called spinal cord progenitor cells marked by oligodendrocyte lineage transcription factor 2 (Olig2). However, it is difficult to identify the spinal cord progenitor cell in vitro as they are present transiently and further transform into other neuronal (interneuron) and glial (oligodendrocyte) lineages during development. In the present study, we try to generated Olig2+ spinal cord progenitor cells from human induced neural stem cells (iNSCs) and identify those spinal cord progenitor cells in vitro Materials and Methods: Human peripheral blood mononuclear cells (PBMCs) were converted into induced neural stem cells (iNSCs), after they were identified by immunostaining using neural stem cell markers such as Nestin, Sox1, Sox2, iNSCs were transformed into Olig2+ spinal cord progenitor cells in 3 weeks by using small molecules. Results: Olig2+ spinal cord progenitor cells could expand for at least five passages and remained in a dividing state over a considerable period of time; in addition, the Olig2+ progenitor cells could mature into O4 and MBP positive oligodendrocytes and HB9 positive motor neurons in a short period. Conclusion: Our research provides a useful protocol for rapid generation of human oligodendrocytes and motor neurons from human iNSCs and demonstrates a progenitor cell model for exploring the origin of motor neurons and oligodendrocyte in vitro, which will contribute to research on the development of spinal cord and regenerative medicine. [ABSTRACT FROM AUTHOR]

Background and Purpose: The circle of Willis (COW) is a crucial mechanism for cerebral collateral circulation. This proof-of-concept study aims to develop and assess an analysis method to characterize the hemodynamics of the arterial segments in the COW by using arterial spin-labeling (ASL) based non-contrast-enhanced dynamic MR angiography (dMRA)., Materials and Methods: The developed analysis method uses a graph model, bootstrap strategy, and ensemble learning methodologies to determine the time curve shift from ASL dMRA to estimate the flow direction within the COW. The performance of the method was assessed on 52 subjects, by using the flow direction, either antegrade or retrograde, derived from 3D phase-contrast MR imaging as the reference., Results: A total of 340 arterial segments in the COW were evaluated, among which 30 (8.8%) had retrograde flow according to 3D phase-contrast MRI. The ASL dMRA-based flow direction estimation has an accuracy, sensitivity, and specificity of 95.47%, 80%, and 96.34%, respectively., Conclusions: Using ASL dMRA and the developed image analysis method to estimate the flow direction in COW is feasible. This study provides a new method to assess the hemodynamics of the COW, which could be useful for the diagnosis and study of cerebrovascular diseases., (© 2024 by American Journal of Neuroradiology.)

Background: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a transmembrane glycoprotein that mediates uptake of oxidized low-density lipoprotein (ox-LDL) into cells. Previous studies had shown that LOX-1 deletion had a potential to inhibit cardiac fibrosis in mouse models of hypertension and myocardial infarction. Whether LOX-1 deletion also affects cardiac fibrosis associated with aging still remains unknown. The aim of this study was to investigate the effect of LOX-1 deletion on myocardial fibrosis in the aged mice. Methods: C57BL/6 mice and LOX-1 knockout (KO) mice with C57BL/6 background were studied to the age of 60 weeks. Both genotypes of aged mice were exposed to angiotensin II (Ang II) or saline for additional 4 weeks. The mice were then sacrificed, and myocardial fibrosis, reactive oxygen species (ROS) and expression of LOX-1, fibronectin, collagens, p22 phox , and gp91 phox were measured. Results: LOX-1 deletion markedly reduced Ang II-mediated rise of blood pressure in the aged mice (vs. saline-treated mice). LOX-1 deletion also limited fibrosis and decreased fibronectin and collagen-3 expression in the hearts of aged mice, but not the expression of collagen-1 and collagen-4. LOX-1 deletion also inhibited ROS production and p22 phox expression. As the aged mice were exposed to Ang II for 4 weeks (resulting in hypertension), LOX-1 deletion more pronounced inhibiting myocardial fibrosis and ROS production, and decreasing expression of fibronectin, collagen-1, collagen-2, collagen-3, p22 phox , and gp91 phox . Conclusion: LOX-1 deletion limited fibrosis and ROS production in the hearts of aged mice. This effect was more pronounced in the aged mice with hypertension induced by Ang II infusion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Tang, Liu, Zhang, Zhang, Lv, Liu, Mehta and Wang.)

Autologous neural stem cells (NSCs) may offer a promising source for deriving dopaminergic (DA) cells for treatment of Parkinson's disease (PD). Methods: By using Sendai virus, human peripheral blood mononuclear cells (PBMNCs) were reprogrammed to induced NSCs (iNSCs), which were then differentiated to dopaminergic neurons in vitro . Whole-genome deep sequencing was performed to search for mutations that had accumulated during the reprogramming and expansion processes. To find the optimal differentiation stage of cells for transplantation, DA precursors obtained at various differentiation time points were tested by engraftment into brains of naïve immunodeficient mice. At last, the safety and efficacy of iNSC-derived DA precursors were tested by transplantation into the striatum of immunodeficient PD mouse models. Results: PBMNC-derived iNSCs showed similar characteristics to fetal NSCs, and were able to specifically differentiate to DA neurons with high efficiency in vitro . The sequencing data proved that no harmful SNVs, Indels and CNVs were generated during the reprogramming and expansion processes. DA precursors obtained between differentiation day 10 to 13 in vitro were most suitable for transplantation when a balanced graft survival and maturation were taken into account. Two weeks after transplantation of DA precursors into mouse PD models, the motor functions of PD mice started to improve, and continued to improve until the end of the experiments. No graft overgrowth or tumor was observed, and a significant number of A9-specific midbrain DA neurons were surviving in the striatum. Conclusion: This study confirmed the efficacy of iNSC-derived DA precursors in a mouse PD model, and emphasized the necessity of genomic sequencing and vigorous safety assessment before any clinical translation using iNSCs., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Autologous dopamine (DA) neurons are a new cell source for replacement therapy of Parkinson's disease (PD). In this study, we tested the safety and efficacy of autologous induced pluripotent stem cell (iPSC)-derived DA cells for treatment of a cynomolgus monkey PD model. Monkey bone marrow mesenchymal cells were isolated and induced to iPSCs, followed by differentiation into DA cells using a method with high efficiency. Autologous DA cells were introduced into the brain of a cynomolgus monkey PD model without immunosuppression; three PD monkeys that had received no grafts served as controls. The PD monkey that had received autologous grafts experienced behavioral improvement compared with that of controls. Histological analysis revealed no overgrowth of grafts and a significant number of surviving A9 region-specific graft-derived DA neurons. The study provided a proof-of-principle to employ iPSC-derived autologous DA cells for PD treatment using a nonhuman primate PD model.