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| Open AccessBicarbonate signalling via G protein-coupled receptor regulates ischaemia-reperfusion injury
The acid–base balance regulates cellular responses, but little has been known about its molecular mechanism. Here, the authors unveil a bicarbonate-sensing GPCR, GPR30, that underlies cerebral ischemia–reperfusion injury by regulating blood flow recovery.
- Airi Jo-Watanabe
- , Toshiki Inaba
- & Takehiko Yokomizo
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Article
| Open AccessFatal iatrogenic cerebral β-amyloid-related arteritis in a woman treated with lecanemab for Alzheimer’s disease
A 79-year-old woman received three doses of lecanemab, an experimental drug for Alzheimer’s disease, and suffered a seizure and cerebral edema. Neuropathological evaluation showed severe cerebral amyloid angiopathy, arteritis and microhemorrhages.
- Elena Solopova
- , Wilber Romero-Fernandez
- & Matthew Schrag
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Article
| Open AccessSingle-nucleus DNA sequencing reveals hidden somatic loss-of-heterozygosity in Cerebral Cavernous Malformations
Here the authors establish somatic loss-of-heterozygosity as a genetic underpinning of Cerebral Cavernous Malformations (CCMs): using single-nucleus DNA sequencing, they show homozygosity of chromosomes 7p and/or 7q leads to biallelic inactivation of CCM genes in resected lesions.
- Andrew K. Ressler
- , Daniel A. Snellings
- & Douglas A. Marchuk
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Article
| Open AccessDeep-learning based detection of vessel occlusions on CT-angiography in patients with suspected acute ischemic stroke
AI may enhance diagnostic accuracy in medicine. Here, authors developed an AI model to detect and localise vessel occlusions in patients with suspected ischemic stroke, outperforming commercial tools on pseudo-prospective multicenter benchmarking.
- Gianluca Brugnara
- , Michael Baumgartner
- & Philipp Vollmuth
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| Open AccessTherapeutic blood-brain barrier modulation and stroke treatment by a bioengineered FZD4-selective WNT surrogate in mice
The WNT/b-catenin pathway is essential for bloodbrain barrier (BBB) and blood-retina barrier (BRB) function. A bioengineered FZD4-selective WNT surrogate demonstrated systemic efficacy during BRB and ischemic stroke BBB dysfunction in mice.
- Jie Ding
- , Sung-Jin Lee
- & Calvin J. Kuo
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Article
| Open AccessEvidence against a temporal association between cerebrovascular disease and Alzheimer’s disease imaging biomarkers
Whether a relationship exists between cerebrovascular disease and Alzheimer’s disease has been a source of controversy. Here, the authors show there is a very weak temporal relationship between the progression of Alzheimer’s disease biomarkers and those of cerebrovascular disease.
- Petrice M. Cogswell
- , Emily S. Lundt
- & Clifford R. Jack Jr
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Article
| Open AccessA randomized trial of Trendelenburg position for acute moderate ischemic stroke
The effect of head positioning in acute stroke is controversial. Here, the authors report the results of a clinical trial suggesting that the procedure, initiated within 24 hours of onset, is safe and feasible, but does not improve functional outcome in acute moderate stroke patients with large artery atherosclerosis.
- Hui-Sheng Chen
- , Nan-Nan Zhang
- & Thanh N. Nguyen
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| Open AccessElectroacupuncture improves swallowing function in a post-stroke dysphagia mouse model by activating the motor cortex inputs to the nucleus tractus solitarii through the parabrachial nuclei
Difficulty swallowing after stroke and the neural circuitry underlying this is not fully understood. Here the authors demonstrate, using a mouse model, a potential neural circuit mechanism for effects of electroacupuncture on swallowing behaviour in post-stroke dysphagia.
- Lulu Yao
- , Qiuping Ye
- & Nenggui Xu
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Article
| Open AccessHypothermia evoked by stimulation of medial preoptic nucleus protects the brain in a mouse model of ischaemia
Developing brain-protective hypothermia is a medical challenge. Here, the authors show that deep brain stimulation of a particular brain area is a new way to trigger the body into a hibernation-like state with reduced body temperature and brain protection in a mouse model of stroke.
- Shuai Zhang
- , Xinpei Zhang
- & Sheng-Tao Hou
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Article
| Open AccessGenome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities
Aortic distensibility is a risk factor for multiple cardiovascular events, but the genetic etiology is not well understood. Here, the authors identify genetic variants linked to aortic distensibility, highlighting mechanistic pathways and causal relationships between distensibility and both aortic aneurysms and brain small vessel disease.
- Catherine M. Francis
- , Matthias E. Futschik
- & Paul M. Matthews
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Article
| Open AccessNon-productive angiogenesis disassembles Aß plaque-associated blood vessels
Aß are extracellular deposits relevant in Alzheimer’s disease (AD). This study shows that Aß plaques are hubs of endothelial disassembly that induce non-productive angiogenesis. This process is aided by the microglia and unchained by reduced presenilin function, a trait of AD, in endothelial cells.
- Maria I. Alvarez-Vergara
- , Alicia E. Rosales-Nieves
- & Alberto Pascual
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Article
| Open AccessAlterations of gut microbiota contribute to the progression of unruptured intracranial aneurysms
Unruptured intracranial aneurysm (UIA) is a life-threatening cerebrovascular condition. Here the authors report altered gut microbiota including low abundance of Hungatella hathewayi in patients with UIAs, and show that supplementation with Hungatella hathewayi or the metabolite taurine prevents UIAs in mice.
- Hao Li
- , Haochen Xu
- & Jingzhou Chen
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Article
| Open AccessPermissive microbiome characterizes human subjects with a neurovascular disease cavernous angioma
Gut microbiome has been linked to cavernous angioma (CA), a common vascular disease, but the role in humans remains unclear. Here, the authors combine 16S rRNA sequencing and shotgun metagenomics to profile the microbiome in a large cohort of human subjects with and without CA, and among subjects with different CA clinical features.
- Sean P. Polster
- , Anukriti Sharma
- & Issam A. Awad
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Article
| Open AccessGenome-wide association study of MRI markers of cerebral small vessel disease in 42,310 participants
Cerebral small vessel disease (CSVD) is a major cause of stroke and associated with structural changes of the brain. Here, Persyn et al. perform genome-wide association studies for magnetic resonance imaging (MRI) markers of CSVD, explore genetic correlations and prioritize candidate genes.
- Elodie Persyn
- , Ken B. Hanscombe
- & Hugh S. Markus
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Article
| Open AccessNon-Invasive MRI of Blood–Cerebrospinal Fluid Barrier Function
The blood–cerebrospinal fluid barrier (BCSFB) is an important interface for brain homeostasis. Here the authors describe a non-invasive MRI technique for the quantitative assessment of BCSFB function.
- P. G. Evans
- , M. Sokolska
- & J. A. Wells
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Article
| Open AccessLoss of the transcription factor RBPJ induces disease-promoting properties in brain pericytes
Pericytes are perivascular cells essential for blood-brain barrier maintenance. Here Diéguez-Hurtado et al. show that depletion of the transcription factor RBPJ in pericytes affects their molecular identity and disturbs endothelial cell behaviour, inducing the formation of vascular lesions in the brain.
- Rodrigo Diéguez-Hurtado
- , Katsuhiro Kato
- & Ralf H. Adams
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Article
| Open AccessEndothelial cell clonal expansion in the development of cerebral cavernous malformations
Cerebral cavernous malformation is a vascular disease characterized by capillary-venous cavernomas in the central nervous system. Here the authors show that cavernomas display benign tumor characteristics and originate from the clonal expansion of mutated endothelial progenitors which can attract surrounding wild-type cells, inducing their mesenchymal transition and leading to growth of the cavernoma.
- Matteo Malinverno
- , Claudio Maderna
- & Elisabetta Dejana
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Article
| Open AccessA conserved CCM complex promotes apoptosis non-autonomously by regulating zinc homeostasis
Cerebral Cavernous Malformations (CCM) are often caused by mutations in CCM1/KRIT1. Here, Chapman et al. elegantly show that the CCM complex promotes apoptosis by regulating zinc homeostasis and storage via a conserved mechanism that likely generates the pathological defects observed in CCM.
- Eric M. Chapman
- , Benjamin Lant
- & W. Brent Derry
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Review Article
| Open AccessThe molecular basis of endothelial cell plasticity
Vascular endothelium possesses remarkable plasticity in response to cues from its surroundings, leading to great heterogeneity of endothelial cells in different vascular beds. Here the authors explain the molecular basis of endothelial plasticity during embryogenesis and in various diseases.
- Elisabetta Dejana
- , Karen K. Hirschi
- & Michael Simons
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Article
| Open AccessRare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals
The Tohoku Medical Megabank Organization establishes a biobank with detailed patient health care and genome information. Here the authors analyse whole-genome sequences of 1,070 Japanese individuals, allowing them to catalogue 21 million single-nucleotide variants including 12 million novel ones.
- Masao Nagasaki
- , Jun Yasuda
- & Masayuki Yamamoto
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Article
| Open AccessBruton’s tyrosine kinase is essential for NLRP3 inflammasome activation and contributes to ischaemic brain injury
Activation of inflammasome contributes to several pathologies. Here, the authors show that Bruton’s tyrosine kinase is essential for NLRP3 inflammasome activation, and that blocking it with the FDA-approved inhibitor ibrutinib limits tissue damage in a mouse model of ischaemic stroke.
- Minako Ito
- , Takashi Shichita
- & Rimpei Morita
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Article
| Open AccessHistamine H3 receptors aggravate cerebral ischaemic injury by histamine-independent mechanisms
Histamine H3 receptor dysregulation is a hallmark of pathological conditions in the central nervous system, and H3 receptor antagonism is neuroprotective. Here Chen et al.show that histamine-independent H3 receptor activation can enhance neuronal cell death during cerebral ischaemia by suppressing autophagy.
- Haijing Yan
- , Xiangnan Zhang
- & Zhong Chen
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Article
| Open AccessThe collagen-binding protein of Streptococcus mutans is involved in haemorrhagic stroke
The risk factors associated with both ischemic and haemorrhagic stroke are not fully understood. Here a certain strain of the bacteria,Streptococcus mutans, which expresses a collagen-binding protein, is shown to be associated with haemorrhagic stroke in both animal models and human patients.
- Kazuhiko Nakano
- , Kazuya Hokamura
- & Takashi Ooshima