Review
Biochemistry & Molecular Biology
Rawan Tarawneh
Summary: Alzheimer's disease (AD) models propose that abnormal protein aggregation is the primary event in AD, but recent evidence indicates that reduced blood flow due to capillary loss and endothelial dysfunction may be the early and primary events in AD pathogenesis. These vascular factors may precede amyloid and tau aggregation and contribute to neuronal and synaptic injury. Clinical studies have shown that endothelial dysfunction is closely related to cognitive outcomes in AD, suggesting that promoting endothelial repair in early AD may be a potential therapeutic strategy to slow disease progression. This review examines evidence from various studies supporting the vascular hypothesis of AD and emphasizes the need for further investigations into its role in the disease.
Article
Geriatrics & Gerontology
Kira Shaw, Katie Boyd, Silvia Anderle, Matthew Hammond-Haley, Davina Amin, Orla Bonnar, Catherine N. Hall
Summary: The function of different components of the neurovascular unit gradually changes along the vascular tree, without clear transitions between different types of vessels. Different functions are performed by wide areas of the vasculature, and alterations in cell morphology suggest functional specializations.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Neurosciences
Gary P. P. Morris, Catherine G. G. Foster, Jo-Maree Courtney, Jessica M. M. Collins, Jake M. M. Cashion, Lachlan S. S. Brown, David W. W. Howells, Gabriele C. C. DeLuca, Alison J. J. Canty, Anna E. E. King, Jenna M. M. Ziebell, Brad A. A. Sutherland
Summary: We discovered a subset of microglia, called pericyte-associated microglia (PEM), that closely associate with pericytes. PEM are present in the brain and spinal cord, and their number is reduced in the superior frontal cortex in Alzheimer's disease (AD). This may contribute to vascular dysfunction in neurodegenerative diseases.
Review
Pharmacology & Pharmacy
Gema Mondejar-Parreno, Angel Cogolludo, Francisco Perez-Vizcaino
Summary: The functional diversity of K+ channels in the pulmonary vasculature is attributed to various factors including gene expression, alternative RNA splicing, post-transcriptional modifications, and the presence of different subunits. These channels play a crucial role in regulating membrane potential and controlling the dilation or contraction of pulmonary arteries. Impaired K+ channel activity is a key factor in the development of pulmonary hypertension, which can result from mutation, downregulation of expression, or decreased channel current due to various vasoactive factors or drug exposure. Restoring K+ channel function is a potential therapeutic strategy for pulmonary hypertension.
PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Neurosciences
Cara D. Nielson, Andy Y. Shih
Summary: This article describes a method to study pericyte function in the living mouse brain. By optically ablating individual pericytes, the researchers can examine their roles in the local capillary network and remaining cells.
FRONTIERS IN NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Francesca Del Gaudio, Dongli Liu, Urban Lendahl
Summary: Notch signalling is a highly conserved mechanism that plays important roles in differentiation and homeostasis in various tissues. This review focuses on the recent advances in understanding the roles of Notch signalling in the vasculature. It discusses the regulation of blood vessel generation and remodelling, as well as the contribution of dysregulated Notch signalling to vascular diseases. Furthermore, it highlights the current gaps in knowledge and challenges in understanding the role of Notch in the vasculature.
Review
Biochemistry & Molecular Biology
Arash Y. Tehrani, Marco A. Ciufolini, Pascal Bernatchez
Summary: Marfan syndrome is a connective tissue disorder caused by mutations in the FBN1 gene, with progressive aortic root widening being a serious manifestation. Our understanding of MFS-associated aortic remodeling remains fragmented, with nitric oxide synthase-related changes potentially playing a significant role in the pathogenesis.
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
(2021)
Article
Physiology
Robert G. Underly, Andy Y. Shih
Summary: Nitric oxide plays important roles in normal vascular physiology but can also contribute to vascular pathology in disease; during brain ischemia, aberrant nitric oxide levels can cause cellular injury, and the rapid activation of MMP-9 at capillary pericyte somata during ischemia involves both nitric oxide synthase and new protein synthesis.
FRONTIERS IN PHYSIOLOGY
(2021)
Review
Neurosciences
Parand Zarekiani, Henrique Nogueira Pinto, Elly M. Hol, Marianna Bugiani, Helga E. de Vries
Summary: The neurovascular unit (NVU) is a highly organized multicellular system in the brain, consisting of neuronal, glial, and vascular cells. Dysfunctions of the NVU occur in various neurological disorders, but little is known about its function in leukodystrophies. Human induced pluripotent stem cells (hiPSC) offer a solution to overcome the limitations of studying leukodystrophies, providing a biologically relevant human context and preserving the patient's genetic background. This review focuses on the NVU function in leukodystrophies and the use of hiPSC-derived models to study neurovascular pathophysiology in these diseases.
FLUIDS AND BARRIERS OF THE CNS
(2022)
Article
Endocrinology & Metabolism
Elisa Vazquez-Liebanas, Khayrun Nahar, Giacomo Bertuzzi, Annika Keller, Christer Betsholtz, Maarja Andaloussi Mae
Summary: PDGFB expression in endothelial cells is critical for maintaining pericyte coverage and normal BBB function in adult quiescent microvasculature, but does not lead to vessel dilation, arterio-venous skewing, and microvascular calcification.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)
Article
Physiology
D. Ryan King, Meghan W. Sedovy, Xinyan Eaton, Luke S. Dunaway, Miranda E. Good, Brant E. Isakson, Scott R. Johnstone
Summary: The arterial vasculature consists of different types of arteries and arterioles that play a crucial role in controlling blood pressure. The communication between endothelial cells and smooth muscle cells within the vessel walls regulates arterial diameter, resistance, and blood pressure. Activation of endothelial cells produces vasodilatory signals, while activation of smooth muscle cells leads to vasoconstriction.
COMPREHENSIVE PHYSIOLOGY
(2022)
Article
Biochemical Research Methods
Lei Tong, Robert A. Hill, Eyiyemisi C. Damisah, Katie N. Murray, Peng Yuan, Angelique Bordey, Jaime Grutzendler
Summary: This protocol outlines tools and procedures for intravital labeling, in vivo calcium imaging, and optogenetics to study mural cells in brain blood vessels. These tools allow for investigation of the physiological and pathophysiological roles of mural cells in various disease models, revealing functional and structural heterogeneity.
Article
Neurosciences
David A. Hartmann, Robert G. Underly, Roger I. Grant, Ashley N. Watson, Volkhard Lindner, Andy Y. Shih
Article
Neurosciences
Robert G. Underly, Manuel Levy, David A. Hartmann, Roger I. Grant, Ashley N. Watson, Andy Y. Shih
JOURNAL OF NEUROSCIENCE
(2017)
Article
Endocrinology & Metabolism
Philipp M. Summers, David A. Hartmann, Edward S. Hui, Xingju Nie, Rachael L. Deardorff, Emilie T. McKinnon, Joseph A. Helpern, Jens H. Jensen, Andy Y. Shih
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2017)
Review
Biochemistry & Molecular Biology
David A. Hartmann, Hyacinth I. Hyacinth, Francesca-Fang Liao, Andy Y. Shih
JOURNAL OF NEUROCHEMISTRY
(2018)
Review
Clinical Neurology
Andy Y. Shih, Hyacinth I. Hyacinth, David A. Hartmann, Susanne J. van Veluw
Article
Cell Biology
Andree-Anne Berthiaume, Roger I. Grant, Konnor P. McDowell, Robert G. Underly, David A. Hartmann, Manuel Levy, Narayan R. Bhat, Andy Y. Shih
Review
Geriatrics & Gerontology
Andree-Anne Berthiaume, David A. Hartmann, Mark W. Majesky, Narayan R. Bhat, Andy Y. Shih
FRONTIERS IN AGING NEUROSCIENCE
(2018)
Review
Neurosciences
David Hartmann, Jana Drummond, Erik Handberg, Sharday Ewell, Lucas Pozzo-Miller
Article
Neurosciences
David A. Hartmann, Andree-Anne Berthiaume, Roger I. Grant, Sarah A. Harrill, Tegan Koski, Taryn Tieu, Konnor P. McDowell, Anna V. Faino, Abigail L. Kelly, Andy Y. Shih
Summary: Capillary pericytes play a role in regulating blood flow by influencing vasoconstriction and dilation. Optogenetic stimulation of these cells leads to decreased luminal diameter and blood flow, affecting the overall modulation of blood flow in the brain.
NATURE NEUROSCIENCE
(2021)
Article
Biology
Philip J. O'Herron, David A. Hartmann, Kun Xie, Prakash Kara, Andy Y. Shih
Summary: This study presents an optical method to manipulate and monitor the contractility of brain arterioles in mice with high spatiotemporal resolution. By expressing the red-shifted excitatory opsin ReaChR and using light pulses for two-photon activation, highly localized arteriole contractions can be achieved. The method can be used to study arteriole contractile dynamics, produce transient focal blood flow reductions, and reshape vasodilatory responses to sensory stimulation.
Article
Clinical Neurology
David A. Hartmann, Meredith Bock, Vanja Douglas, Josiah Gerdts, Biswarathan Ramani, Maulik Shah
Summary: The 67-year-old woman was diagnosed with immune-mediated necrotizing myopathy, coinciding with the discovery of a gastrointestinal stromal tumor (GIST) and positivity for anti-nuclear matrix protein (anti-NXP2).
