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      Sex differences in acute and long‐term brain recovery after concussion

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          Abstract

          Concussion is associated with acute disturbances in brain function and behavior, with potential long‐term effects on brain health. However, it is presently unclear whether there are sex differences in acute and long‐term brain recovery. In this study, magnetic resonance imaging (MRI) was used to scan 61 participants with sport‐related concussion (30 male, 31 female) longitudinally at acute injury, medical clearance to return to play (RTP), and 1‐year post‐RTP. A large cohort of 167 controls (80 male, 87 female) was also imaged. Each MRI session assessed cerebral blood flow (CBF), along with white matter fractional anisotropy (FA) and mean diffusivity (MD). For concussed athletes, the parameters were converted to difference scores relative to matched control subgroups, and partial least squares modeled the main and sex‐specific effects of concussion. Although male and female athletes did not differ in acute symptoms or time to RTP , all MRI measures showed significant sex differences during recovery. Males had greater reductions in occipital‐parietal CBF (mean difference and 95%CI: 9.97 ml/100 g/min, [4.84, 15.12] ml/100 g/min, z = 3.73) and increases in callosal MD (9.07 × 10 −5, [−14.14, −3.60] × 10 −5, z = −3.46), with greatest effects at 1‐year post‐RTP. In contrast, females had greater reductions in FA of the corona radiata (16.50 × 10 −3, [−22.38, −11.08] × 10 −3, z = −5.60), with greatest effects at RTP. These findings provide new insights into how the brain recovers after a concussion, showing sex differences in both the acute and chronic phases of injury.

          Abstract

          This study examined whether there are sex differences in acute and long‐term brain changes after concussion. Male athletes showed greater declines in cerebral blood flow, whereas both sexes showed unique alterations in white matter microstructure. These sex differences were present at acute injury and remained up to 1 year after medical clearance.

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          Most cited references67

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          NODDI: practical in vivo neurite orientation dispersion and density imaging of the human brain.

          This paper introduces neurite orientation dispersion and density imaging (NODDI), a practical diffusion MRI technique for estimating the microstructural complexity of dendrites and axons in vivo on clinical MRI scanners. Such indices of neurites relate more directly to and provide more specific markers of brain tissue microstructure than standard indices from diffusion tensor imaging, such as fractional anisotropy (FA). Mapping these indices over the whole brain on clinical scanners presents new opportunities for understanding brain development and disorders. The proposed technique enables such mapping by combining a three-compartment tissue model with a two-shell high-angular-resolution diffusion imaging (HARDI) protocol optimized for clinical feasibility. An index of orientation dispersion is defined to characterize angular variation of neurites. We evaluate the method both in simulation and on a live human brain using a clinical 3T scanner. Results demonstrate that NODDI provides sensible neurite density and orientation dispersion estimates, thereby disentangling two key contributing factors to FA and enabling the analysis of each factor individually. We additionally show that while orientation dispersion can be estimated with just a single HARDI shell, neurite density requires at least two shells and can be estimated more accurately with the optimized two-shell protocol than with alternative two-shell protocols. The optimized protocol takes about 30 min to acquire, making it feasible for inclusion in a typical clinical setting. We further show that sampling fewer orientations in each shell can reduce the acquisition time to just 10 min with minimal impact on the accuracy of the estimates. This demonstrates the feasibility of NODDI even for the most time-sensitive clinical applications, such as neonatal and dementia imaging. Copyright © 2012 Elsevier Inc. All rights reserved.
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            Blood-Brain Barrier: From Physiology to Disease and Back

            The blood-brain barrier (BBB) prevents neurotoxic plasma components, blood cells, and pathogens from entering the brain. At the same time, the BBB regulates transport of molecules into and out of the central nervous system (CNS), which maintains tightly controlled chemical composition of the neuronal milieu that is required for proper neuronal functioning. In this review, we first examine molecular and cellular mechanisms underlying the establishment of the BBB. Then, we focus on BBB transport physiology, endothelial and pericyte transporters, and perivascular and paravascular transport. Next, we discuss rare human monogenic neurological disorders with the primary genetic defect in BBB-associated cells demonstrating the link between BBB breakdown and neurodegeneration. Then, we review the effects of genes underlying inheritance and/or increased susceptibility for Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease, and amyotrophic lateral sclerosis (ALS) on BBB in relation to other pathologies and neurological deficits. We next examine how BBB dysfunction relates to neurological deficits and other pathologies in the majority of sporadic AD, PD, and ALS cases, multiple sclerosis, other neurodegenerative disorders, and acute CNS disorders such as stroke, traumatic brain injury, spinal cord injury, and epilepsy. Lastly, we discuss BBB-based therapeutic opportunities. We conclude with lessons learned and future directions, with emphasis on technological advances to investigate the BBB functions in the living human brain, and at the molecular and cellular level, and address key unanswered questions.
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              Consensus statement on concussion in sport-the 5(th) international conference on concussion in sport held in Berlin, October 2016.

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                Author and article information

                Contributors
                nchurchill.research@gmail.com
                Journal
                Hum Brain Mapp
                Hum Brain Mapp
                10.1002/(ISSN)1097-0193
                HBM
                Human Brain Mapping
                John Wiley & Sons, Inc. (Hoboken, USA )
                1065-9471
                1097-0193
                12 October 2021
                15 December 2021
                : 42
                : 18 ( doiID: 10.1002/hbm.v42.18 )
                : 5814-5826
                Affiliations
                [ 1 ] Keenan Research Centre for Biomedical Science of St. Michael's Hospital Toronto ON Canada
                [ 2 ] Neuroscience Research Program St. Michael's Hospital Toronto ON Canada
                [ 3 ] Faculty of Kinesiology and Physical Education, University of Toronto Toronto ON Canada
                [ 4 ] Department of Medical Biophysics University of Toronto Toronto ON Canada
                [ 5 ] Physical Sciences Platform Sunnybrook Research Institute, Sunnybrook Health Sciences Centre Toronto ON Canada
                [ 6 ] Faculty of Medicine (Neurosurgery), University of Toronto Toronto ON Canada
                [ 7 ] The Institute of Biomaterials and Biomedical Engineering (IBBME) at the University of Toronto Toronto ON Canada
                Author notes
                [*] [* ] Correspondence

                Nathan W. Churchill, Keenan Research Centre of the Li Ka Shing Knowledge Institute at St. Michael's Hospital Neuroscience Research Program, St. Michael's Hospital, Toronto, ON, Canada.

                Email: nchurchill.research@ 123456gmail.com

                Author information
                https://orcid.org/0000-0001-8481-2505
                Article
                HBM25591
                10.1002/hbm.25591
                8596946
                34643005
                76ca598c-75e3-4f1e-ab9c-2e39e742cf49
                © 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 May 2021
                : 13 February 2021
                : 01 July 2021
                Page count
                Figures: 4, Tables: 3, Pages: 13, Words: 11218
                Funding
                Funded by: Canadian Institute for Military and Veteran Health Research , doi 10.13039/501100015592;
                Award ID: W7714‐145967
                Funded by: Canadian Institutes of Health Research , doi 10.13039/501100000024;
                Award ID: RN294001‐367456
                Award ID: RN356342‐401065
                Funded by: Siemens Healthineers , doi 10.13039/501100011699;
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                December 15, 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.9 mode:remove_FC converted:17.11.2021

                Neurology
                asl,brain injury,concussion,dti,sex differences
                Neurology
                asl, brain injury, concussion, dti, sex differences

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