Article
Geriatrics & Gerontology
Amanda C. Rosehart, Thomas A. Longden, Nick Weir, Jackson T. Fontaine, Anne Joutel, Fabrice Dabertrand
Summary: Research suggests that PGE(2) can induce upstream arteriolar dilation by stimulating capillaries, but its action is inhibited by EP1 receptor antagonists and is also influenced by the strong inward-rectifier K+ channel. In an animal model of cerebral small vessel disease, the response to capillary stimulation with PGE(2) is weakened.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Clinical Neurology
Stephanie Guey, Saskia A. J. Lesnik Oberstein, Elisabeth Tournier-Lasserve, Hugues Chabriat
Summary: This article summarizes the key features for diagnosing hereditary cerebral small vessel diseases in adult stroke patients, describes the main clinical and imaging characteristics of major hereditary cerebral small vessel diseases that can present as stroke, and provides general recommendations for clinical management of affected patients and their relatives.
Article
Clinical Neurology
Jing-Yi Liu, Ming Yao, Yi Dai, Fei Han, Fei-Fei Zhai, Ding-Ding Zhang, Li-Xin Zhou, Jun Ni, Shu-Yang Zhang, Li-Ying Cui, Yi-Cheng Zhu
Summary: A study in a Chinese community-based cohort found a high frequency of rare NOTCH3 variants, with carriers of EGFr-involved variants potentially predisposed to age-related cerebral small vessel disease. These carriers of rare variants also showed higher volume of white matter hyperintensities and heavier burden of cerebral small vessel disease.
Article
Clinical Neurology
Jessica Walsh, Dan J. Tozer, Hasan Sari, Young T. Hong, Anna Drazyk, Guy Williams, N. Jon Shah, John T. O'Brien, Franklin Aigbirhio, Gary Rosenberg, Tim D. Fryer, Hugh S. Markus
Summary: Cerebral small vessel disease is a major cause of stroke and dementia. The study found that in sporadic SVD patients, microglial activation and increased blood-brain barrier permeability occur separately in spatial terms. No evidence of increased blood-brain barrier permeability was found in CADASIL.
Article
Clinical Neurology
Alvin S. Das, Robert W. Regenhardt, Elif Gokcal, Mitchell J. Horn, Nader Daoud, Kristin M. Schwab, Natalia S. Rost, Anand Viswanathan, W. Taylor Kimberly, Joshua N. Goldstein, Alessandro Biffi, Lee H. Schwamm, Jonathan Rosand, Steven M. Greenberg, M. Edip Gurol
Summary: The study found that approximately one-third of IP-IVH patients had cerebral amyloid angiopathy, and 23% had hypertensive small vessel disease. This suggests that both types of small vessel diseases may be associated with IP-IVH.
INTERNATIONAL JOURNAL OF STROKE
(2022)
Article
Biochemistry & Molecular Biology
Hannah R. Ferris, Nathan C. Stine, David C. Hill-Eubanks, Mark T. Nelson, George C. Wellman, Masayo Koide
Summary: Functional hyperemia, which refers to the increase in local blood perfusion in response to enhanced neuronal activity, plays a crucial role in brain health. This study found that the impairment of endothelial epidermal growth factor receptor (EGFR) signaling resulted in crippled functional hyperemia, likely due to depletion of phosphatidylinositol 4,5-bisphosphate (PIP2) and dysfunctional Kir2.1 channels in capillary endothelial cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Mengke Zhang, Ruiwen Che, Wenbo Zhao, Hailiang Sun, Changhong Ren, Jin Ma, Wenbo Hu, Milan Jia, Chuanjie Wu, Xin Liu, Xunming Ji
Summary: This study aimed to explore the relationship between computed tomography (CT)-based cerebral small vessel disease (SVD) markers and the clinical outcomes in patients with cerebral amyloid angiopathy (CAA)-related intracerebral hemorrhage (ICH). The results showed that the SVD markers based on CT could predict the short-term outcome more effectively in patients with CAA-ICH. Further studies are needed to validate these findings and identify modifiable factors for preventing CAA-ICH development.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Multidisciplinary Sciences
Shira Burg, Shir Shapiro, Asher Peretz, Elvira Haimov, Boris Redko, Adva Yeheskel, Luba Simhaev, Hamutal Engel, Avi Raveh, Ariel Ben-Bassat, Michael Murninkas, Rotem Polak, Yoni Haitin, Yoram Etzion, Bernard Attali
Summary: Phosphatidylinositol 4-5 bisphosphate (PIP2) potently activates the SK4 channel by docking to the boundary of the CaM-binding domain. An allosteric blocker, BA6b9, inhibits SK4 channels by interacting with specific residues in the linker S4-S5, preventing proper interaction between the Ca2+-CaM N-lobe and the channel linker region. Inhibition of SK4 channels by targeting drugs to the CaM-PIP2-binding domain may serve as a promising anti-arrhythmic therapy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Clinical Neurology
Jessica Lebenberg, Ruiting Zhang, Lina Grosset, Jean Pierre Guichard, Fanny Fernandes, Eric Jouvent, Hugues Chabriat
Summary: This study developed and validated an automatic segmentation method for quantifying incident lacunes in a severe and progressive form of cerebral small vessel disease. The automatic method accurately identified and quantified the lacunes, providing a fast and efficient approach for measuring incident lacunes in large-scale studies.
FRONTIERS IN NEUROLOGY
(2023)
Article
Geriatrics & Gerontology
Xingfang Guo, Bin Deng, Lizi Zhong, Fen Xie, Qing Qiu, Xiaobo Wei, Wenya Wang, Jiangping Xu, Ganqiang Liu, Wong Peter Tsun Hon, Midori A. Yenari, Shuzhen Zhu, Qing Wang
Summary: This study investigated the relationship between fibrinogen and WMHs in sCSVD and CADASIL patients. The results showed that high levels of plasma fibrinogen are associated with the severity of WMHs in CADASIL patients but not in sCSVD patients, indicating a different role of fibrinogen in disparate subtypes of CSVD.
Article
Clinical Neurology
Anna Dewenter, Mina A. Jacob, Mengfei Cai, Benno Gesierich, Paul Hager, Anna Kopczak, Davina Biel, Michael Ewers, Anil M. Tuladhar, Frank-Erik De Leeuw, Martin Dichgans, Nicolai Franzmeier, Marco Duering
Summary: Fixel-based analysis of diffusion MRI can identify changes in white matter integrity. Neurodegeneration in Alzheimer's disease affects white matter macrostructure, while cerebral small vessel disease affects white matter microstructure. Fiber density reflects the impact of cerebral small vessel disease, while fiber-bundle cross-section is primarily determined by neurodegeneration.
Article
Neurosciences
Paul J. Dunn, Rodney A. Lea, Neven Maksemous, Robert A. Smith, Heidi G. Sutherland, Larisa M. Haupt, Lyn R. Griffiths
Summary: This study identifies a genetic overlap between Alzheimer's disease and cerebral small vessel disease, and identifies ERNI as a novel candidate gene for cerebral small vessel disease.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Cell Biology
Jiajie Xu, Ya Su, Jiayu Fu, Yong Shen, Qiang Dong, Xin Cheng
Summary: Cerebral small vessel diseases (CSVD) are a group of diseases caused by pathologies of intracranial small blood vessels. Traditional explanations for CSVD pathogenesis, including endothelium dysfunction, blood-brain barrier leakage, and the inflammatory response, are not sufficient to explain the complex syndrome and related neuroimaging characteristics. Recent research has focused on the glymphatic pathway, which plays a pivotal role in clearing perivascular fluid and metabolic solutes, and its potential role in CSVD.
AGEING RESEARCH REVIEWS
(2023)
Article
Clinical Neurology
Remco J. Hack, Gido Gravesteijn, Minne N. Cerfontaine, Mark A. Santcroos, Laura Gatti, Anna Kopczak, Anna Bersano, Marco Duering, Julie W. Rutten, Saskia A. J. Lesnik Oberstein
Summary: A novel three-tiered risk classification for NOTCH3 variants associated with CADASIL disease prediction has been identified in this study.
Article
Neurosciences
Haotian Xin, Hongwei Wen, Mengmeng Feng, Yian Gao, Chaofan Sui, Nan Zhang, Changhu Liang, Lingfei Guo
Summary: This study aimed to investigate alterations in functional brain networks in patients with cerebral small vessel disease (CSVD) and assess the relationship between functional impairment and topological network changes. The results showed that patients with CSVD and cerebral microbleeds (CMBs) exhibited disrupted balance between local specialization and global integration in the functional connectivity networks, as well as altered nodal betweenness centrality in certain brain regions. These findings contribute to our understanding of the pathophysiological mechanisms underlying CSVD.
HUMAN BRAIN MAPPING
(2022)
Article
Geriatrics & Gerontology
Amanda C. Rosehart, Thomas A. Longden, Nick Weir, Jackson T. Fontaine, Anne Joutel, Fabrice Dabertrand
Summary: Research suggests that PGE(2) can induce upstream arteriolar dilation by stimulating capillaries, but its action is inhibited by EP1 receptor antagonists and is also influenced by the strong inward-rectifier K+ channel. In an animal model of cerebral small vessel disease, the response to capillary stimulation with PGE(2) is weakened.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Meeting Abstract
Physiology
Osama F. Harraz, Nicholas R. Klug, Amanda Senatore, Masayo Koide, Mark T. Nelson
JOURNAL OF GENERAL PHYSIOLOGY
(2022)
Editorial Material
Physiology
Daniela Carnevale, Fabrice Dabertrand, Clotilde Lecrux, Jean-Luc Morel
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Hematology
Selen C. Muratoglu, Marc F. Charette, Zorina S. Galis, Adam S. Greenstein, Alan Daugherty, Anne Joutel, Beth A. Kozel, Donna M. Wilcock, Emily C. Collins, Farzaneh A. Sorond, Gareth R. Howell, Hyacinth I. Hyacinth, Kent K. C. Lloyd, Kurt R. Stenmark, Manfred Boehm, Mark L. Kahn, Roderick Corriveau, Sara Wells, Timothy J. Bussey, Stacey J. Sukoff Rizzo, M. Luisa Iruela-Arispe
Summary: Clinical investigations have shown that vascular-associated medical conditions are significant risk factors for dementia. However, the specific cognitive impairments associated with certain types of vascular deficiencies are still unclear. To address this, the National Heart, Lung, and Blood Institute has developed animal models to study vascular disease and its underlying causes. These models could be used as tools to link specific vascular signaling pathways with cognitive and neurobehavioral deficits related to dementia.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Clinical Neurology
Aniket Mishra, Cecile Duplaa, Dina Vojinovic, Hideaki Suzuki, Muralidharan Sargurupremraj, Nuno R. Zilhao, Shuo Li, Traci M. Bartz, Xueqiu Jian, Wei Zhao, Edith Hofer, Katharina Wittfeld, Sarah E. Harris, Sandra Van der Auwera-Palitschka, Michelle Luciano, Joshua C. Bis, Hieab H. H. Adams, Claudia L. Satizabal, Rebecca F. Gottesman, Piyush G. Gampawar, Robin Bulow, Stefan Weiss, Miao Yu, Mark E. Bastin, Oscar L. Lopez, Meike W. Vernooij, Alexa S. Beiser, Uwe Voelker, Tim Kacprowski, Aicha Soumare, Jennifer A. Smith, David S. Knopman, Zoe Morris, Yicheng Zhu, Jerome Rotter, Carole Dufouil, Maria Valdes Hernandez, Susana Munoz Maniega, Mark Lathrop, Erik Boerwinkle, Reinhold Schmidt, Masafumi Ihara, Bernard Mazoyer, Qiong Yang, Anne Joutel, Elizabeth Tournier-Lasserve, Lenore J. Launer, Ian J. Deary, Thomas H. Mosley, Philippe Amouyel, Charles S. DeCarli, Bruce M. Psaty, Christophe Tzourio, Sharon L. R. Kardia, Hans J. Grabe, Alexander Teumer, Cornelia M. van Duijn, Helena Schmidt, Joanna M. Wardlaw, M. Arfan Ikram, Myriam Fornage, Vilmundur Gudnason, Sudha Seshadri, Paul M. Matthews, William T. Longstreth, Thierry Couffinhal, Stephanie Debette
Summary: Cerebral small vessel disease is a leading cause of stroke and cognitive decline. A comprehensive gene study identified multiple loci and genes associated with the disease. Mendelian randomization supported the causal relationship between disease severity and increased risk of stroke and Alzheimer's disease. Further functional evaluation suggested a potential role of TRIM47 in the pathophysiology of cerebral small vessel disease.
Article
Cardiac & Cardiovascular Systems
Osama F. Harraz, Nicholas R. Klug, Amanda J. Senatore, David C. Hill-Eubanks, Mark T. Nelson
Summary: This study shows that Piezo1 channels act as mechanosensors in central nervous system capillaries, initiating crucial Ca2+ signals and having a profound impact on blood flow control.
CIRCULATION RESEARCH
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Terry Sehaid, Sanchayita Mitra, Margot DeBot, Alexis Cralley, Christopher Erickson, Fabrice Dabertrand, Jackson Fontaine, Angelo D'Alessandro, Kirk Hansen, Kenneth Jones, Angela Sauaia
Article
Multidisciplinary Sciences
Takahiro Masuda, Lukas Amann, Gianni Monaco, Roman Sankowski, Ori Staszewski, Martin Krueger, Francesca Del Gaudio, Liqun He, Neil Paterson, Elisa Nent, Francisco Fernandez-Klett, Ayato Yamasaki, Maximilian Frosch, Maximilian Fliegauf, Lance Fredrick Pahutan Bosch, Hatice Ulupinar, Nora Hagemeyer, Dietmar Schreiner, Cayce Dorrier, Makoto Tsuda, Claudia Grothe, Anne Joutel, Richard Daneman, Christer Betsholtz, Urban Lendahl, Klaus-Peter Knobeloch, Tim Laemmermann, Josef Priller, Katrin Kierdorf, Marco Prinz
Summary: This study reveals the ontogenetic relationships and development of different subsets of macrophages in the central nervous system (CNS). Microglia and meningeal macrophages share a common prenatal progenitor, while perivascular macrophages originate from the perinatal meningeal macrophages after birth in an integrin-dependent manner. The presence of arterial vascular smooth muscle cells is crucial for the establishment of perivascular macrophages.
Article
Neurosciences
Danielle A. Jeffrey, Jackson T. Fontaine, Fabrice Dabertrand
Summary: This article introduces an ex vivo method that replicates the dynamics of blood vessels in the brain. By using this method, researchers were able to observe changes in smooth muscle cells and pericytes in the arterial wall without interfering with neuronal tissue. This method is crucial for studying the differences of mural cells based on their location in microvasculature.
Article
Cell Biology
Ashwini Hariharan, Colin D. Robertson, Daniela C. G. Garcia, Thomas A. Longden
Summary: This study demonstrates the important role of capillary thin-strand pericytes in regulating brain hemodynamics and responding to local energy deficits. Activation of KATP channels in pericytes leads to hyperpolarization and increased blood flow to prevent energetic shortfalls.
Editorial Material
Neurosciences
Oliver Bracko, Osama F. Harraz
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Review
Physiology
Thomas A. Longden, Guiling Zhao, Ashwini Hariharan, W. Jonathan Lederer
Summary: Pericytes play a key role in regulating blood flow in the brain and heart, and possess unique morphological features such as tunneling nanotubes and tunneling microtubes. They are involved in electro-metabolic signaling, which links tissue metabolic state with blood flow regulation. However, there are still unresolved questions in this field that need further investigation.
ANNUAL REVIEW OF PHYSIOLOGY
(2023)
Article
Neurosciences
Eleonora Grandi, Manuel F. Navedo, Jeffrey J. Saucerman, Donald M. Bers, Nipavan Chiamvimonvat, Rose E. Dixon, Dobromir Dobrev, Ana M. Gomez, Osama F. Harraz, Bence Hegyi, David K. Jones, Trine Krogh-Madsen, Walter Lee Murfee, Matthew A. Nystoriak, Nikki G. Posnack, Crystal M. Ripplinger, Rengasayee Veeraraghavan, Seth Weinberg
Summary: This white paper summarises the outcomes of the seventh UC Davis Cardiovascular Research Symposium on Systems Approach to Understanding Cardiovascular Disease and Arrhythmia. The Symposium aimed to bring together experts in cardiovascular biomedicine to focus on the diversity and signaling involved in cardiovascular function. The paper presents an overview of major cell types, explores the complexity of cardiovascular development and disease at various levels, and discusses technological innovations for advancing understanding of integrated cardiovascular function and dysfunction.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Meeting Abstract
Peripheral Vascular Disease
Lowri Elizabeth Evans, Jade Taylor, Fabrice Dabertrand, Harry Pritchard, Ingo Schiessl, Stuart Allan, Adam Greenstein
JOURNAL OF HYPERTENSION
(2023)
Article
Medicine, Research & Experimental
Fumiaki Oka, Jeong Hyun Lee, Izumi Yuzawa, Mei Li, Daniel von Bornstaedt, Katharina Eikermann-Haerter, Tao Qin, David Y. Chung, Homa Sadeghian, Jessica L. Seidel, Takahiko Imai, Doga Vuralli, Rosangela M. Platt, Mark T. Nelson, Anne Joutel, Sava Sakadzic, Cenk Ayata
Summary: This study found that CADASIL mutations worsen outcomes after ischemic stroke, likely due to a higher blood flow threshold needed to maintain tissue viability compared to wild type mice. Mutants developed larger infarcts and worse neurological deficits regardless of age or sex. Perfusion deficits during occlusion were similar between mutants and wild type controls. However, mutants had a higher cerebral blood flow threshold below which infarction occurred, suggesting increased sensitivity to ischemia. The study also revealed a higher frequency of peri-infarct spreading depolarizations in CADASIL mutants, indicating a defect in extracellular K+ clearance. These findings suggest that CADASIL is associated with enhanced vulnerability to ischemic injury and abnormal extracellular ion homeostasis.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
