Article
Clinical Neurology
Ruoyao Cao, Peng Qi, Yun Jiang, Shen Hu, Gengfan Ye, Yaxin Zhu, Ling Li, Zilong You, Juan Chen
Summary: The quantitative evaluation of collateral circulation on tMIP CTA is associated with clinical outcomes in AIS patients with endovascular treatments.
FRONTIERS IN NEUROLOGY
(2021)
Review
Clinical Neurology
Gino Maguida, Ashfaq Shuaib
Summary: The collateral circulation is important in ischemic stroke as it maintains perfusion to brain tissue and allows for a longer time window for effective therapies. However, enhancing it as a therapeutic target remains a challenge. Assessment of the collateral circulation is now routine in neuroimaging for stroke, providing a more complete picture of the pathophysiology and aiding in treatment selection and outcome prediction. This review aims to provide an updated approach to the collateral circulation and highlight ongoing research with potential clinical applications.
Review
Clinical Neurology
Francesco Motolese, Jacopo Lanzone, Antonio Todisco, Mariagrazia Rossi, Francesca Santoro, Alessandro Cruciani, Fioravante Capone, Vincenzo Di Lazzaro, Fabio Pilato
Summary: Ischemic stroke is a complex process involving vessel occlusion and subsequent changes in brain tissue. The penumbra, or hypo-perfused tissue surrounding the core of the stroke, can potentially be recovered with restored blood flow. Neurophysiological changes occur in both the core and penumbra, as well as in overall neural networks due to disrupted connectivity.
FRONTIERS IN NEUROLOGY
(2023)
Review
Clinical Neurology
Simone M. Uniken Venema, Jan Willem Dankbaar, Aad van der Lugt, Diederik W. J. Dippel, H. Bart van der Worp
Summary: The extent of collateral circulation in patients with acute ischemic stroke affects their clinical outcomes, and a good collateral circulation is associated with greater benefit of thrombolysis and endovascular treatment. Computed tomography and magnetic resonance imaging allow for rapid assessment of collateral extent and cerebral perfusion, however, the importance of collateral circulation in clinical decision-making may be underestimated due to the use of coarse and rater-dependent grading methods.
Article
Endocrinology & Metabolism
James E. Faber, Hua Zhang, James G. Xenakis, Timothy A. Bell, Pablo Hock, Fernando Pardo-Manuel de Villena, Martin T. Ferris, Wojciech Rzechorzek
Summary: Collateral blood flow varies greatly among humans and mice, which is caused by genetic background-dependent differences. The use of closely related inbred strains limits the understanding of this variation. The Collaborative Cross (CC) multiparent mouse genetic reference panel was developed to address this limitation. This study provides a comprehensive set of candidate genes for future investigations of collateral insufficiency.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Article
Clinical Neurology
Stanley Hughwa Hung, Sharon Kramer, Emilio Werden, Bruce C. V. Campbell, Amy Brodtmann
Summary: Favorable cerebral collateral circulation is important in preventing infarction and improving clinical outcomes after stroke. This article discusses the potential association between pre-stroke physical activity and cerebral collateral circulation in ischemic stroke, as well as opportunities for future research in this area.
FRONTIERS IN NEUROLOGY
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Jin Seok Yi, Hee Jong Ki, Yoo Sung Jeon, Jeong Jin Park, Taek-Jun Lee, Jin Tae Kwak, Sang Bong Lee, Hyung Jin Lee, In Seong Kim, Joo Hyun Kim, Ji Sung Lee, Hong Gee Roh, Hyun Jeong Kim
Summary: This study evaluated the ability of collateral maps to predict lesion growth and penumbra after acute anterior circulation ischemic strokes. The results showed that collateral perfusion grades were associated with lesion growth, and the collateral ratio had a high concordance correlation coefficient, making it useful for personalized application of recanalization treatments.
EUROPEAN RADIOLOGY
(2023)
Review
Geriatrics & Gerontology
Truong An Bui, Glen C. Jickling, Ian R. Winship
Summary: Stroke is a major cause of death and disability worldwide. Restoring blood flow through recanalization is the only acute treatment for cerebral ischemia. Activation of peripheral immune cells, particularly neutrophils, may contribute to microcirculatory failure and ineffective recanalization. Age is associated with higher mortality after endovascular therapies, and the interaction between stroke injury, aging, and inflammation is complex. Understanding these interactions is important for developing protective treatments.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Clinical Neurology
Jae Eun Sim, Jong-Won Chung, Woo-Keun Seo, Oh Young Bang, Gyeong-Moon Kim
Summary: This study investigated the factors related to initial collateral flow in patients with acute ischemic stroke and analyzed the results according to stroke etiology. The results showed that elevated initial systolic blood pressure was associated with poor cerebral collateral flow and more severe symptoms in the cardioembolism group, but not in the large artery atherosclerosis group.
FRONTIERS IN NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hayden Waller, Thomas Blankers, Mingzi Xu, Kerry L. Shaw
Summary: Sexual signalling traits and their associated genetic components are crucial for the speciation process. However, our understanding of the genetic basis of variable sexual signalling traits linked to speciation is limited. This study provides new genetic evidence of Quantitative Trait Loci (QTL) underlying divergent sexual signalling behaviour in Hawaiian crickets. By sequencing RNA in the brain and central nervous system, candidate genes associated with pulse rate are identified, shedding light on the genetic processes driving reproductive isolation and species diversity.
INSECT MOLECULAR BIOLOGY
(2023)
Article
Geriatrics & Gerontology
Chanchan Li, Xiaozhu Hao, Luyi Lin, Chengfeng Sun, Hai Yu, Zhenwei Yao, Xiaoyuan Feng, Yanmei Yang
Summary: The study found that AIS patients with poor collateral circulation on CTA and high relative PS on CTP were at a higher risk for hemorrhagic transformation, indicating the importance of assessing both parameters for predicting HT in MCAO patients.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Review
Medicine, General & Internal
Marilena Mangiardi, Adriano Bonura, Gianmarco Iaccarino, Michele Alessiani, Maria Cristina Bravi, Domenica Crupi, Francesca Romana Pezzella, Sebastiano Fabiano, Enrico Pampana, Francesco Stilo, Guido Alfano, Sabrina Anticoli
Summary: Cerebral collateral circulation is a network of blood vessels that ensures adequate blood flow in the brain when the main arteries fail, as seen in ischemic stroke. The extent of this collateral circulation plays a crucial role in determining treatment efficacy and outcomes. The use of advanced brain imaging techniques has enabled a better understanding of these networks, leading to more effective therapeutic strategies. This narrative review discusses the pathophysiology, clinical aspects, and potential diagnostic and therapeutic roles of collateral circulation in acute ischemic stroke.
Article
Clinical Neurology
Daniel Guisado-Alonso, Pol Camps-Renom, Raquel Delgado-Mederos, Esther Granell, Luis Prats-Sanchez, Alejandro Martinez-Domeno, Marina Guasch-Jimenez, M. Victoria Acosta, Anna Ramos-Pachon, Joan Marti-Fabregas
Summary: This study aimed to determine whether the degree of collateral circulation is associated with blood pressure at admission in acute ischemic stroke patients treated with endovascular treatment and to determine its prognostic value. The results showed that admission systolic blood pressure and higher baseline NIHSS were associated with a worse collateral score. A good collateral score was associated with a favorable outcome.
FRONTIERS IN NEUROLOGY
(2022)
Article
Clinical Neurology
Yao Xu, Jianhong Yang, Xiang Gao, Jie Sun, Qing Shang, Qing Han, Yuefei Wu, Jichuan Li, Tianqi Xu, Yi Huang, Yuning Pan, Mark W. Parson, Longting Lin
Summary: This study aimed to find and validate an optimal collateral time measurement method for patients with acute ischemic stroke. Through studying 106 patients with complete large vessel occlusions, it was found that perfusion computed tomography can accurately measure collateral time and has better performance in clinical outcome prediction compared to other methods.
FRONTIERS IN NEUROLOGY
(2023)
Article
Medicine, General & Internal
Mersedeh Bahr-Hosseini, Kambiz Nael, Gozde Unal, Marco Iacoboni, David S. Liebeskind, Marom Bikson, Jeffrey L. Saver
Summary: This study conducted a first-in-human pilot trial using individualized high-definition cathodal transcranial direct current stimulation (HD C-tDCS) for the treatment of acute ischemic stroke. The results showed that HD C-tDCS was efficiently initiated and well tolerated in emergency settings, with potential benefits in salvaging the ischemic penumbra. These findings support further investigation of HD C-tDCS in larger clinical trials.
Article
Genetics & Heredity
K. P. Thompson, J. Nelson, H. Kim, L. Pawlikowska, D. A. Marchuk, M. T. Lawton, Marie E. Faughnan
Summary: Chronic gastrointestinal bleeding, anemia, and symptomatic liver vascular malformations are associated with increased mortality in HHT patients, while pulmonary arteriovenous malformations and brain vascular malformations do not seem to impact mortality.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Medicine, Research & Experimental
Wenqing Li, Robert Shenkar, Mathew R. Detter, Thomas Moore, Christian Benavides, Rhonda Lightle, Romuald Girard, Nicholas Hobson, Ying Cao, Yan Li, Erin Griffin, Carol Gallione, Joseph M. Zabramski, Mark H. Ginsberg, Douglas A. Marchuk, Issam A. Awad
Summary: Propranolol, a pleiotropic beta-adrenergic blocker, has shown promising results in reducing cerebral cavernous malformations in animal models such as zebrafish and mice, possibly due to its beta 1 adrenergic antagonism. These findings suggest that propranolol or other beta 1-selective antagonists may be beneficial in treating CCM disease.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Clinical Neurology
Lindsay F. Smegal, Alison J. Sebold, Adrienne M. Hammill, Csaba Juhasz, Warren D. Lo, Daniel K. Miles, Angus A. Wilfong, Alex Levin, Brian Fisher, Karen L. Ball, Anna L. Pinto, Anne M. Comi
Summary: The study analyzed the use of neurological drug treatment in SWS patients across different demographic and SWS characteristic groups. Results showed that variables such as sex, ethnicity, and brain, skin, and eye involvement can impact medication use. The study also found that a history of neurosurgery, bilateral brain involvement, and family history may affect the number of antiseizure medications used by patients.
PEDIATRIC NEUROLOGY
(2021)
Article
Multidisciplinary Sciences
Aileen A. Ren, Daniel A. Snellings, Yourong S. Su, Courtney C. Hong, Marco Castro, Alan T. Tang, Matthew R. Detter, Nicholas Hobson, Romuald Girard, Sharbel Romanos, Rhonda Lightle, Thomas Moore, Robert Shenkar, Christian Benavides, M. Makenzie Beaman, Helge Mueller-Fielitz, Mei Chen, Patricia Mericko, Jisheng Yang, Derek C. Sung, Michael T. Lawton, J. Michael Ruppert, Markus Schwaninger, Jakob Koerbelin, Michael Potente, Issam A. Awad, Douglas A. Marchuk, Mark L. Kahn
Summary: Vascular malformations are caused by increased signaling through the PI3K-mTOR pathway and loss of function of the CCM complex, which are found in the majority of human CCMs. Using mouse models, researchers discovered that the formation of CCMs can be effectively blocked by the mTORC1 inhibitor rapamycin.
Article
Clinical Neurology
Sara Keranen, Santeri Suutarinen, Rahul Mallick, Johanna P. Laakkonen, Diana Guo, Ludmila Pawlikowska, Behnam Rezai Jahromi, Tuomas Rauramaa, Seppo Yla-Herttuala, Doug Marchuk, Timo Krings, Timo Koivisto, Michael Lawton, Ivan Radovanovic, Helen Kim, Marie E. Faughnan, Juhana Frosen
Summary: COX2 expression is found in the majority of bAVMs and is associated with inflammation, but not hemorrhage. Further studies are needed to understand the role of COX2 signaling in the pathobiology and clinical course of bAVMs.
ACTA NEUROCHIRURGICA
(2021)
Article
Peripheral Vascular Disease
F. Galeffi, D. A. Snellings, S. E. Wetzel-Strong, N. Kastelic, J. Bullock, C. J. Gallione, P. E. North, D. A. Marchuk
Summary: Sturge-Weber syndrome (SWS) is a rare neuro-cutaneous disorder caused by GNAQ gene mutations. A new Q209R mutation was identified, which may contribute to signal activation but is less common. Additionally, different GNAQ mutations exhibit varying levels of activation but have similar downstream effects.
Article
Genetics & Heredity
Carol J. Gallione, Matthew R. Detter, Adrienne Sheline, Henrietta M. Christmas, Cornelia Lee, Douglas A. Marchuk
Summary: Cerebral cavernous malformations (CCM) are vascular malformations that can occur sporadically or be inherited. This study found that a gene deletion mutation in seemingly unrelated patients may have originated from a founder mutation that occurred centuries ago on the North American continent. Further investigation is needed for the inclusion of another gene, NACAD, in this deletion for these patients.
Letter
Medicine, Research & Experimental
Robert Shenkar, Thomas Moore, Christian Benavides, Rhonda Lightle, Matthew R. Detter, Nicholas Hobson, Romuald Girard, Dorothy DeBiasse, Mary Patrucco, Carol Gallione, Joseph M. Zabramski, Douglas A. Marchuk, Issam A. Awad
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Jillian L. Cardinell, Joel M. Ramjist, Chaoliang Chen, Weisong Shi, Nhu Q. Nguyen, Tiffany Yeretsian, Matthew Choi, David Chen, Dewi S. Clark, Anne Curtis, Helen Kim, Marie E. Faughnan, Victor X. D. Yang
Summary: This study utilizes optical coherence tomography (OCT) to image and quantitatively characterize dermal HHT lesions in order to understand the dynamic processes of the disease. Refined metrics specifically tailored for HHT were developed based on a pilot study and presented alongside preliminary results in this paper. The use of this imaging modality provides a non-invasive and efficient method to analyze and understand HHT lesions.
SCIENTIFIC REPORTS
(2022)
Article
Clinical Neurology
Sharbel G. Romanos, Abhinav Srinath, Ying Li, Bingqing Xie, Chang Chen, Yan Li, Thomas Moore, Dehua Bi, Je Yeong Sone, Rhonda Lightle, Nick Hobson, Dongdong Zhang, Janne Koskimaki, Le Shen, Sara McCurdy, Catherine Chinhchu Lai, Agnieszka Stadnik, Kristina Piedad, Julian Carrion-Penagos, Abdallah Shkoukani, Daniel Snellings, Robert Shenkar, Dinanath Sulakhe, Yuan Ji, Miguel A. Lopez-Ramirez, Mark L. Kahn, Douglas A. Marchuk, Mark H. Ginsberg, Romuald Girard, Issam A. Awad
Summary: This study identifies homologous differentially expressed (DE) plasma miRNAs that can reflect germline mutations in familial cerebral cavernous malformation (CCM) in preclinical murine models and patients. The findings suggest the potential development of translatable circulating biomarkers for monitoring and restoring gene function in CCM and other diseases.
TRANSLATIONAL STROKE RESEARCH
(2023)
Article
Genetics & Heredity
Han Kyu Lee, Do Hoon Kwon, David L. Aylor, Douglas A. Marchuk
Summary: This study establishes an in vivo evaluation platform in mice and verifies that human RABEP2 can rescue the volume and collateral vessel phenotypes of mice with ischemic stroke. Additionally, it identifies damaging coding variants that affect the function of RABEP2, expanding the potential targets for ischemic stroke therapeutics development.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Cardiac & Cardiovascular Systems
Sean P. Reuter, Mark H. Soonpaa, Dorothy Field, Ed Simpson, Michael Rubart-von der Lohe, Han Kyu Lee, Arthi Sridhar, Stephanie M. Ware, Nick Green, Xiaochun Li, Susan Ofner, Douglas A. Marchuk, Kai C. Wollert, Loren J. Field
Summary: Genetic analysis found that Tnni3k expression increases cardiomyocyte S-phase activity after injury. This study may help guide the development of therapeutic interventions for cardiac regeneration.
Article
Genetics & Heredity
K. P. Thompson, J. Sykes, P. Chandakkar, P. Marambaud, N. T. Vozoris, D. A. Marchuk, M. E. Faughnan
Summary: The study did not demonstrate the effectiveness of doxycycline as a treatment for epistaxis in patients with HHT, although hemoglobin levels were significantly higher during treatment. Secondary analyses may help guide future trials in HHT.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Genetics & Heredity
Sarah E. Wetzel-Strong, Francesca Galeffi, Christian Benavides, Mary Patrucco, Jessica L. Bullock, Carol J. Gallione, Han Kyu Lee, Douglas A. Marchuk
Summary: Sturge-Weber Syndrome (SWS) is a non-inherited syndrome characterized by vascular malformations in the face, leptomeninges, or choroid. A mouse model for SWS has been created using gene targeting to express the GNAQ p.R183Q mutation. These mice survive and show no obvious vascular defects, supporting the paradominant inheritance hypothesis for SWS and providing a model for studying postnatal phenotypes and developing therapies.
Review
Chemistry, Medicinal
Matthew J. Hagan, Robert Shenkar, Abhinav Srinath, Sharbel G. Romanos, Agnieszka Stadnik, Mark L. Kahn, Douglas A. Marchuk, Romuald Girard, Issam A. Awad
Summary: Cerebral cavernous malformations (CCMs) are hemorrhagic neurovascular lesions that affect more than 1 million people in the United States. Rapamycin inhibits CCM development and bleeding in murine models. The appropriate dosage to modify disease phenotype remains unknown. Current approved indications by the U.S. Food and Drug Administration and clinicaltrials.gov were queried for rapamycin human dosing for various indications. In humans, low daily doses of <2 mg/day or trough level targets <15 ng/mL were typically used for benign indications akin to CCM disease, with relatively low complication rates. Higher oral doses in humans, used for organ rejection, result in higher complication rates. Oral dosing in mice, between 2 and 4 mg/kg/day, achieved blood trough levels in the 5-15 ng/mL range, a concentration likely to be targeted in human studies to treat CCM. Preclinical studies are needed utilizing dosing strategies which achieve blood levels corresponding to likely human dosimetry.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2022)
