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Bone Marrow-Derived Alk1 Mutant Endothelial Cells and Clonally Expanded Somatic Alk1 Mutant Endothelial Cells Contribute to the Development of Brain Arteriovenous Malformations in Mice
AbstractWe have previously demonstrated that deletion of activin receptor-like kinase 1 (Alk1) or endoglin in a fraction of endothelial cells (ECs) induces brain arteriovenous malformations (bAVMs) in adult mice upon angiogenic stimulation. Here, we addressed three related questions: (1) couldAlk1− mutant bone marrow (BM)-derived ECs (BMDECs) cause bAVMs? (2) is Alk1− ECs clonally expended during bAVM development? and (3) is the number of mutant ECs correlates to bAVM severity? For the first question, we transplanted BM fromPdgfbiCreER;Alk12f/2f mice (EC-specific tamoxifen-inducible Cre withAlk1-floxed alleles) into wi...
Source: Translational Stroke Research - October 21, 2021 Category: Neurology Source Type: research

Deletion of muscarinic acetylcholine receptor 3 in microglia impacts brain ischemic injury.
In conclusion, our data suggest that the upregulation of m3R in microglia and monocytes in stroke has a beneficial effect on the clinical outcome in male mice. PMID: 32927021 [PubMed - as supplied by publisher]
Source: Brain, Behavior, and Immunity - September 10, 2020 Category: Neurology Authors: Costa A, Haage V, Yang S, Wegner S, Ersoy B, Ugursu B, Rex A, Kronenberg G, Gertz K, Endres M, Wolf SA, Kettenmann H Tags: Brain Behav Immun Source Type: research

An Embolic Stroke in a Patient With PROC p.Lys193del
We report a 58-year-old woman who suddenly developed brain infarction with weakness of the left lower extremity and left perioral dysesthesia during postoperative tamoxifen therapy for breast cancer and prednisolone therapy for rheumatoid arthritis. Diffusion-weighted images detected multiple areas of hyperintensity in the posterior circulation system of the brain. Despite extensive examinations, we could not identify any embolic sources except hypoplasia of the right vertebral artery. We found decreased activity of protein C against its antigen level (activity: 59% versus antigen: 122%) with enhanced activity of coagulati...
Source: Journal of Stroke and Cerebrovascular Diseases - February 10, 2020 Category: Neurology Authors: Kana Ueki, Kuniyuki Nakamura, Yoshinobu Wakisaka, Shinichi Wada, Yoji Yoshikawa, Shinya Matsumoto, Taeko Hotta, Dongchong Kang, Takanari Kitazono, Tetsuro Ago Tags: Case Report Source Type: research

Using Dental Pulp Stem Cells for Stroke Therapy
Conclusion and Future Perspectives Stem cell-based therapy is a promising alternative for stroke treatment. While stem cells from different sources, including induced PSC, ESC, MSC, and NSC, have been investigated, using NSC and enhancing the natural mechanisms is most appropriate for brain repair. In preclinical models of stroke, stem cell transplantation has led to positive outcomes through a variety of cellular and molecular mechanisms, many being mediated by the array of beneficial factors produced by the cells. Recent advances in cellular reprogramming have provided alternative sources of NSC to be investigated, allo...
Source: Frontiers in Neurology - April 28, 2019 Category: Neurology Source Type: research

Interleukin-1 mediates ischaemic brain injury via distinct actions on endothelial cells and cholinergic neurons
Publication date: Available online 16 November 2018Source: Brain, Behavior, and ImmunityAuthor(s): Raymond Wong, Nikolett Lénárt, Laura Hill, Lauren Toms, Graham Coutts, Bernadett Martinecz, Eszter Császár, Gábor Nyiri, Athina Papaemmanouil, Ari Waisman, Werner Müller, Markus Schwaninger, Nancy Rothwell, Sheila Francis, Emmanuel Pinteaux, Adam Denes, Stuart M. AllanAbstractThe cytokine interleukin-1 (IL-1) is a key contributor to neuroinflammation and brain injury, yet mechanisms by which IL-1 triggers neuronal injury remain unknown. Here we induced conditional deletion of IL-1R1 in brain endothelial cells, neurons a...
Source: Brain, Behavior, and Immunity - November 16, 2018 Category: Neurology Source Type: research

Interleukin-1 mediates ischaemic brain injury via distinct actions on endothelial cells and cholinergic neurons.
Abstract The cytokine interleukin-1 (IL-1) is a key contributor to neuroinflammation and brain injury, yet mechanisms by which IL-1 triggers neuronal injury remain unknown. Here we induced conditional deletion of IL-1R1 in brain endothelial cells, neurons and blood cells to assess site-specific IL-1 actions in a model of cerebral ischaemia in mice. Tamoxifen treatment of IL-1R1 floxed (fl/fl) mice crossed with mice expressing tamoxifen-inducible Cre-recombinase under the Slco1c1 promoter resulted in brain endothelium-specific deletion of IL-1R1 and a significant decrease in infarct size (29%), blood-brain barrier ...
Source: Brain, Behavior, and Immunity - November 16, 2018 Category: Neurology Authors: Wong R, Lénárt N, Hill L, Toms L, Coutts G, Martinecz B, Császár E, Nyiri G, Papaemmanouil A, Waisman A, Müller W, Schwaninger M, Rothwell N, Francis S, Pinteaux E, Denes A, Allan SM Tags: Brain Behav Immun Source Type: research

Selective knockout of astrocytic Na+/H+ exchanger isoform 1 reduces astrogliosis, BBB damage, infarction, and improves neurological function after ischemic stroke
In this study, we created a Nhe1flox/flox (Nhe1f/f) mouse line with exon 5 of Nhe1 flanked with two loxP sites and selective ablation of Nhe1 in astrocytes was achieved by crossing Nhe1f/f mice with Gfap‐CreERT2 Cre‐recombinase mice. Gfap‐CreERT2+/−;Nhe1f/f mice at postnatal day 60–90 were treated with either corn oil or tamoxifen (Tam, 75 mg/kg/day, i.p.) for 5 days. After 30 days post‐injection, mice underwent transient middle cerebral artery occlusion (tMCAO) to induce ischemic stroke. Compared with the oil‐vehicle group (control), Tam‐treated Gfap‐CreERT2+/−;Nhe1f/f (Nhe1 KO) mice developed signifi...
Source: Glia - September 19, 2017 Category: Neurology Authors: Gulnaz Begum, Shanshan Song, Shaoxia Wang, Hanshu Zhao, Mohammad Iqbal H. Bhuiyan, Eric Li, Rachel Nepomuceno, Qing Ye, Ming Sun, Michael Joseph Calderon, Donna B. Stolz, Claudette St. Croix, Simon C. Watkins, Yinhuai Chen, Pingnian He, Gary E. Shull, Dan Tags: RESEARCH ARTICLE Source Type: research

De Novo Cerebrovascular Malformation in the Adult Mouse After Endothelial Alk1 Deletion and Angiogenic Stimulation Brief Reports
Conclusions— Deletion of Alk1 in EC in adult mice leads to an increased local EC proliferation during brain angiogenesis and de novo brain AVM.
Source: Stroke - February 24, 2014 Category: Neurology Authors: Chen, W., Sun, Z., Han, Z., Jun, K., Camus, M., Wankhede, M., Mao, L., Arnold, T., Young, W. L., Su, H. Tags: Cerebrovascular disease/stroke, Animal models of human disease, Genetically altered mice, Aneurysm, AVM, hematoma Brief Reports Source Type: research