Publications

Hope Center Member Publications

Scopus list of publications for December 3, 2023

Multi-scale measurement of stiffness in the developing ferret brain” (2023) Scientific Reports

Multi-scale measurement of stiffness in the developing ferret brain
(2023) Scientific Reports, 13 (1), art. no. 20583, . 

Walter, C.a , Balouchzadeh, R.a , Garcia, K.E.b , Kroenke, C.D.c , Pathak, A.a , Bayly, P.V.a

a Mechanical Engineering and Materials Science, Washington University, St. Louis, United States
b Radiology and Imaging Sciences, Indiana University School of Medicine, Evansville, IN, United States
c Advanced Imaging Research Center and Oregon National Primate Research Center Division of Neuroscience, Oregon Health and Science University, Portland, OR, United States

Abstract
Cortical folding is an important process during brain development, and aberrant folding is linked to disorders such as autism and schizophrenia. Changes in cell numbers, size, and morphology have been proposed to exert forces that control the folding process, but these changes may also influence the mechanical properties of developing brain tissue. Currently, the changes in tissue stiffness during brain folding are unknown. Here, we report stiffness in the developing ferret brain across multiple length scales, emphasizing changes in folding cortical tissue. Using rheometry to measure the bulk properties of brain tissue, we found that overall brain stiffness increases with age over the period of cortical folding. Using atomic force microscopy to target the cortical plate, we found that the occipital cortex increases in stiffness as well as stiffness heterogeneity over the course of development and folding. These findings can help to elucidate the mechanics of the cortical folding process by clarifying the concurrent evolution of tissue properties. © 2023, The Author(s).

Funding details
CMMI -154857
National Institutes of HealthNIHR01 NS111948, R35 GM128764, T32 EB028092

Document Type: Article
Publication Stage: Final
Source: Scopus

Molecular Diagnostic Yield of Exome Sequencing in Patients With Congenital Hydrocephalus: A Systematic Review and Meta-Analysis” (2023) JAMA Network Open

Molecular Diagnostic Yield of Exome Sequencing in Patients With Congenital Hydrocephalus: A Systematic Review and Meta-Analysis
(2023) JAMA Network Open, 6 (11), p. e2343384. 

Greenberg, A.B.W.a , Mehta, N.H.b , Allington, G.a b , Jin, S.C.c d , Moreno-De-Luca, A.e , Kahle, K.T.a f g

a Department of Neurosurgery, Massachusetts General Hospital, Boston, United States
b Department of Pathology, Yale University School of Medicine, New Haven, CT, United States
c Department of Genetics, Washington University School of Medicine, St Louis, MO, United States
d Department of Pediatrics, Washington University School of Medicine, St Louis, MO, United States
e Department of Radiology, Neuroradiology Section, Kingston Health Sciences Centre, Queen’s University Faculty of Health Sciences, Kingston, Ontario, Canada
f Broad Institute of MIT and Harvard, Cambridge, MA, United States
g Harvard Center for Hydrocephalus and Neurodevelopmental Disorders, Massachusetts General Hospital, Boston, United States

Abstract
Importance: Exome sequencing (ES) has been established as the preferred first line of diagnostic testing for certain neurodevelopmental disorders, such as global developmental delay and autism spectrum disorder; however, current recommendations are not specific to or inclusive of congenital hydrocephalus (CH). Objective: To determine the diagnostic yield of ES in CH and whether ES should be considered as a first line diagnostic test for CH. Data Sources: PubMed, Cochrane Library, and Google Scholar were used to identify studies published in English between January 1, 2010, and April 10, 2023. The following search terms were used to identify studies: congenital hydrocephalus, ventriculomegaly, cerebral ventriculomegaly, primary ventriculomegaly, fetal ventriculomegaly, prenatal ventriculomegaly, molecular analysis, genetic cause, genetic etiology, genetic testing, exome sequencing, whole exome sequencing, genome sequencing, microarray, microarray analysis, and copy number variants. Study Selection: Eligible studies included those with at least 10 probands with the defining feature of CH and/or severe cerebral ventriculomegaly that had undergone ES. Studies with fewer than 10 probands, studies of mild or moderate ventriculomegaly, and studies using genetic tests other than ES were excluded. A full-text review of 68 studies was conducted by 2 reviewers. Discrepancies were resolved by consensus. Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Meta-Analysis of Observational Studies in Epidemiology guidelines were used by 2 reviewers to extract data. Data were synthesized using a random-effects model of single proportions. Data analysis occurred in April 2023. Main Outcomes and Measures: The primary outcome was pooled diagnostic yield. Additional diagnostic yields were estimated for specific subgroups on the basis of clinical features, syndromic presentation, and parental consanguinity. For each outcome, a 95% CI and estimate of interstudy heterogeneity (I2 statistic) was reported. Results: From 498 deduplicated and screened records, 9 studies with a total of 538 CH probands were selected for final inclusion. The overall diagnostic yield was 37.9% (95% CI, 20.0%-57.4%; I2 = 90.1). The yield was lower for isolated and/or nonsyndromic cases (21.3%; 95% CI, 12.8%-31.0%; I2 = 55.7). The yield was higher for probands with reported consanguinity (76.3%; 95% CI, 65.1%-86.1%; I2 = 0) than those without (16.2%; 95% CI, 12.2%-20.5%; I2 = 0). Conclusions and Relevance: In this systematic review and meta-analysis of the diagnostic yield of ES in CH, the diagnostic yield was concordant with that of previous recommendations for other neurodevelopmental disorders, suggesting that ES should also be recommended as a routine diagnostic adjunct for patients with CH.

Document Type: Article
Publication Stage: Final
Source: Scopus

Skull bone marrow channels as immune gateways to the central nervous system” (2023) Nature Neuroscience

Skull bone marrow channels as immune gateways to the central nervous system
(2023) Nature Neuroscience, 26 (12), pp. 2052-2062. 

Mazzitelli, J.A.a b c d , Pulous, F.E.e f , Smyth, L.C.D.a b , Kaya, Z.e f , Rustenhoven, J.g , Moskowitz, M.A.e f h , Kipnis, J.a b c d , Nahrendorf, M.e f i j

a Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
b Center for Brain Immunology and Glia (BIG), Washington University School of Medicine, St. Louis, MO, United States
c Medical Scientist Training Program, Washington University School of Medicine, St. Louis, MO, United States
d Neuroscience Graduate Program, Washington University School of Medicine, St. Louis, MO, United States
e Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
f Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
g Department of Pharmacology and Clinical Pharmacology, The University of Auckland, Auckland, New Zealand
h Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
i Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
j Department of Internal Medicine I, University Hospital Wuerzburg, Wuerzburg, Germany

Abstract
Decades of research have characterized diverse immune cells surveilling the CNS. More recently, the discovery of osseous channels (so-called ‘skull channels’) connecting the meninges with the skull and vertebral bone marrow has revealed a new layer of complexity in our understanding of neuroimmune interactions. Here we discuss our current understanding of skull and vertebral bone marrow anatomy, its contribution of leukocytes to the meninges, and its surveillance of the CNS. We explore the role of this hematopoietic output on CNS health, focusing on the supply of immune cells during health and disease. © 2023, Springer Nature America, Inc.

Funding details
National Institutes of HealthNIHAT010416, HL139598, HL142494, NS096967, NS108419, NS127808
Cure Alzheimer’s FundCAF

Document Type: Article
Publication Stage: Final
Source: Scopus