Article
Neurosciences
Ashley L. Ware, Keith Owen Yeates, Ken Tang, Ayushi Shukla, Adrian Onicas, Sunny Guo, Naomi Goodrich-Hunsaker, Nishard Abdeen, Miriam H. Beauchamp, Christian Beaulieu, Bruce Bjornson, William Craig, Mathieu Dehaes, Quynh Doan, Sylvain Deschenes, Stephen B. Freedman, Bradley G. Goodyear, Jocelyn Gravel, Andree-Anne Ledoux, Roger Zemek, Catherine Lebel
Summary: In this study, the largest sample to date was used to investigate the white matter microstructural changes and their relation to persistent symptoms after pediatric mTBI. The results showed that white matter microstructural changes suggesting neuroinflammation and axonal swelling occurred chronically and continued 6 months post injury in children with mTBI, especially in younger children with persistent symptoms. The white matter microstructure appears more organized in children without persistent symptoms, indicating better clinical outcomes.
HUMAN BRAIN MAPPING
(2022)
Review
Radiology, Nuclear Medicine & Medical Imaging
Eunkyung Kim, Roh-Eul Yoo, Min Yong Seong, Byung-Mo Oh
Summary: Diffusion tensor imaging studies of mild traumatic brain injury (mTBI) in adults show a high variability in reported white matter integrity changes, with long-term neurodegenerative processes and possible recovery. Longitudinal cohort studies are needed for further understanding of brain changes after mTBI.
EUROPEAN JOURNAL OF RADIOLOGY
(2022)
Article
Critical Care Medicine
James J. Gugger, Alexa E. Walter, Drew Parker, Nishant Sinha, Justin Morrison, Jeffrey Ware, Andrea L. C. Schneider, Dmitriy Petrov, Danielle K. Sandsmark, Ragini Verma, Ramon Diaz-Arrastia
Summary: Traumatic brain injury is a global health issue causing chronic complications and long-term disability. It is important to identify biomarkers that can predict poor recovery and guide the development of neuroprotective therapies.
JOURNAL OF NEUROTRAUMA
(2023)
Review
Medicine, General & Internal
Sung-Ho Jang, Min-Jye Cho
Summary: This review paper discusses the application of diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) in the diagnosis of traumatic axonal injury (TAI) in individuals with concussion or mild traumatic brain injury (mTBI). While several hundred DTI-based studies have reported TAI in concussion or mTBI, there are fewer case studies focusing on individual patients. The summary of these studies suggests that DTI can be used as a non-invasive tool for determining the presence and severity of TAI in individual patients with concussion or mTBI. However, certain conditions need to be met for an accurate diagnosis, and further studies are required to improve the precision of TAI diagnosis in individual patients.
Review
Cell Biology
Sung Ho Jang, You Sung Seo
Summary: Diffusion tensor tractography is a valuable method to evaluate axonal injury in concussion (mTBI) patients. It reveals characteristic features such as tearing, narrowing, and discontinuations of neural tracts, which provide insights into the extent and patterns of axonal injury. Axonal injury in concussion (mTBI) patients is characterized by their occurrence in long neural tracts and multiple injuries. However, the corticospinal tract discontinuation is commonly observed in diffuse axonal injury, while partial tearing and narrowing in subcortical white matter are frequently observed in concussion (mTBI) patients. These differences suggest that the forces causing axonal injury in concussion (mTBI) patients are weaker than those in diffuse axonal injuries. Additionally, the presence of collateral branches in concussion (mTBI) patients indicates a relatively weaker impact on the brain compared to diffuse axonal injury. The characteristics of axonal injury in concussion (mTBI) patients reviewed in this study provide valuable supplementary information for the diagnosis of axonal injury in concussion (mTBI) patients.
NEURAL REGENERATION RESEARCH
(2022)
Article
Clinical Neurology
Amy E. Jolly, Maria Balaet, Adriana Azor, Daniel Friedland, Stefano Sandrone, Neil S. N. Graham, Karl Zimmerman, David J. Sharp
Summary: This study introduces a pipeline for assessing the presence of axonal injury in traumatic brain injury patients, revealing that the majority of patients have axonal injury in the chronic and subacute phases. Patients with axonal injury exhibit significantly poorer cognitive and functional outcomes.
Review
Health Care Sciences & Services
Sung Ho Jang, Dong Hyun Byun
Summary: This study reviewed traumatic axonal injury (TAI) in patients with concussion. DTI provides valuable data for the diagnosis of TAI in patients with concussion, but further research is needed to find a diagnostic method that does not require a brain biopsy for live confirmation of TAI.
Article
Neurosciences
Jiachen Zhuo, Li Jiang, Chandler Sours Rhodes, Steven Roys, Karthikamanthan Shanmuganathan, Hegang Chen, Jerry L. Prince, Neeraj Badjatia, Rao P. Gullapalli
Summary: This study found significant reductions in thalamic and hippocampal volumes in patients with mTBI at 1 month post-injury, with changes in thalamic volumes correlating with symptom and functional outcome measures at 6 months. These results suggest that the thalamus may play a key role in the structural and functional deficits seen in mTBI patients, serving as a potential biomarker for assessing the efficacy of new therapeutic interventions.
Article
Medicine, General & Internal
Sung Ho Jang, Seong Ho Kim, Hyeok Gyu Kwon
Summary: This study found a high diagnostic sensitivity of traumatic axonal injury (TAI) of the spinothalamic tract (STT) in patients with mild traumatic brain injury (TBI) suffering from central pain symptoms using diffusion tensor tractography (DTT). However, the generalizability of the study results may be limited by the small number of subjects who visited the university hospital and the constraints of DTT technology.
Article
Clinical Neurology
Stephanie S. G. Brown, Kristen Dams-O'Connor, Eric Watson, Priti Balchandani, Rebecca E. Feldman
Summary: This case study investigates the structural effects of traumatic brain injury using pre-injury and post-injury 7 Tesla MRI longitudinal data for the first time. Findings include initial volumetric changes, decreased structural connectivity, and reduced microstructural order that return to baseline 8 months post-injury, demonstrating in-depth metrics of physiological recovery. Default mode, salience, occipital, and executive function network alterations reflect patient-reported hypersomnolence, reduced cognitive processing speed, and dizziness.
FRONTIERS IN NEUROLOGY
(2021)
Article
Clinical Neurology
Jung Hyun Park, Yun Jung Bae, Ji Su Kim, Woo Sang Jung, Jin Wook Choi, Tae Hoon Roh, Namkyu You, Se-Hyuk Kim, Miran Han
Summary: The DTI-ALPS method is useful for evaluating glymphatic system impairment and quantifying its activity in patients with TBI. The study found that patients with TBI had a significantly lower ALPS index compared to healthy controls, and this was correlated with the presence of subarachnoid hemorrhage and diffuse axonal injury. There was also a weak positive correlation between the ALPS index and GCS scores.
Article
Neurosciences
Yusuf Osmanlioglu, Drew Parker, Jacob A. Alappatt, James J. Gugger, Ramon R. Diaz-Arrastia, John Whyte, Junghoon J. Kim, Ragini Verma
Summary: Traumatic brain injury (TBI) is a major public health problem characterized by the shearing of axons across the white matter, leading to cognitive deficits. Assessing network-wide structural connectivity disruptions in TBI is necessary for personalized treatment and rehabilitation planning. A novel connectomic measure called network normality score (NNS) captures the integrity of structural connectivity in TBI patients by leveraging the diffuseness of axonal injury and the heterogeneity of the disease.
HUMAN BRAIN MAPPING
(2022)
Article
Medicine, General & Internal
Sung Ho Jang, Han Do Lee
Summary: In this study, injury of the CPCT was investigated in patients with mild TBI using DTT, demonstrating differences in FA and FN values among patient groups. The findings suggest the utility of DTT for evaluating CPCT in patients with ataxia after mTBI, where conventional brain MRI may not reveal abnormalities.
Article
Clinical Neurology
Ana Luiza Zaninotto, Daphine Centola Grassi, Dante Duarte, Priscila Aparecida Rodrigues, Ellison Cardoso, Fabricio Stewan Feltrin, Vinicius Monteiro de Paula Guirado, Fabiola Bezerra de Carvalho Macruz, Maria Concepcion Garcia Otaduy, Claudia da Costa Leite, Wellingson Silva Paiva, Celi Santos Andrade
Summary: DTI parameters in the corpus callosum were found to differ between individuals with diffuse axonal injury (DAI) and healthy controls, as well as between patients with moderate and severe DAI. Changes in DTI parameters were observed over time in DAI patients, but no significant correlation was found with psychiatric outcome scores.
NEUROLOGICAL SCIENCES
(2022)
Article
Clinical Neurology
Juho Dahl, Olli Tenovuo, Jussi P. Posti, Jussi Hirvonen, Ari J. Katila, Janek Frantzen, Henna-Riikka Maanpaa, Riikka Takala, Eliisa Loyttyniemi, Jussi Tallus, Virginia Newcombe, David K. Menon, Peter J. Hutchinson, Mehrbod Mohammadian
Summary: Cerebral microbleeds are associated with the clinical severity of traumatic brain injury but have a weaker association with white matter integrity.
FRONTIERS IN NEUROLOGY
(2022)
Article
Chemistry, Medicinal
Brandon M. Taoka, Wen-Lian Wu, Jinsong Hao, Martin Dolmaski, Hongwu Wang, Dorthy Levorse, Peter Orth, Lynn A. Hyde, Brad Smith, Maria S. Michener, Matthew E. Kennedy, Eric M. Parker, Jared N. Cumming
Summary: This paper explores the structure-activity relationships of novel fluoroalkyl substituents at the C2 position of iminothiazine dioxide beta secretase inhibitors, highlighting the impact of reduced amidine basicity on Pgp, cell potency, and efficacy in preclinical in vivo animal models. The findings provide valuable insights into the mechanisms of action of these inhibitors.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Mitchell H. Keylor, Anmol Gulati, Solomon D. Kattar, Rebecca E. Johnson, Ryan W. Chau, Kaila A. Margrey, Michael J. Ardolino, Cayetana Zarate, Kelsey E. Poremba, Vladimir Simov, Gregori J. Morriello, John J. Acton, Barbara Pio, Xin Yan, Rachel L. Palte, Spencer E. McMinn, Lisa Nogle, Charles A. Lesburg, Donovon Adpressa, Shishi Lin, Santhosh Neelamkavil, Ping Liu, Jing Su, Laxminarayan G. Hegde, Janice D. Woodhouse, Robert Faltus, Tina Xiong, Paul J. Ciaccio, Jennifer Piesvaux, Karin M. Otte, Harold B. Wood, Matthew E. Kennedy, David Jonathan Bennett, Erin F. DiMauro, Matthew J. Fell, Peter H. Fuller
Summary: The study successfully discovered brain-penetrant molecules with candidate-quality, high selectivity against the kinome, potency- and selectivity-enhancing design elements, and encouraging brain penetration in preclinical models.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Neurosciences
Katie R. Zarbock, Jessica H. Han, Ajay P. Singh, Sydney P. Thomas, Barbara B. Bendlin, John M. Denu, John-Paul J. Yu, Federico E. Rey, Tyler K. Ulland
Summary: This study assessed the direct impact of TMAO on AD progression and found that TMAO could affect AD pathology by reducing neurite density.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Endocrinology & Metabolism
Tsubasa Tomoto, Aryan Verma, Kayla Kostroske, Takashi Tarumi, Neena R. Patel, Evan P. Pasha, Jonathan Riley, Cynthia D. Tinajero, Linda S. Hynan, Karen M. Rodrigue, Kristen M. Kennedy, Denise C. Park, Rong Zhang
Summary: This study found that one-year progressive, moderate-to-vigorous aerobic exercise training has positive effects on cerebral blood flow, central arterial stiffness, and cognitive performance. In cognitively normal older adults, aerobic exercise training increased cerebral blood flow, decreased carotid arterial stiffness and cerebrovascular resistance, and was associated with improved memory function.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Article
Neurosciences
Arman P. Kulkarni, Gyujoon Hwang, Cole J. Cook, Rosaleena Mohanty, Akhil Guliani, Veena A. Nair, Barbara B. Bendlin, Elizabeth Meyerand, Vivek Prabhakaran
Summary: In this study, a unique approach based on variance analyses was proposed to investigate the genetic influence on individual differences in brain functional connectivity. The findings suggest that genetic factors play a larger role in brain functional connectivity in males, while environmental factors have a greater impact in females. Moreover, the study reveals that environmental influences on individual differences may outweigh genetic influences in the frontal and overall brain regions.
HUMAN BRAIN MAPPING
(2023)
Article
Clinical Neurology
M. Yuan, Kristen M. Kennedy
Summary: This study used geospatial tools and landmarks to assess environmental complexity and predict cognitive status. The results showed that street length, circuity, and points of interest were associated with dementia. Therefore, environmental complexity plays an important role in the development of Alzheimer's disease.
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2023)
Article
Clinical Neurology
P. A. Rowley, M. J. Paukner, L. B. Eisenmenger, A. S. Field, R. J. Davidson, S. C. Johnson, S. Asthana, N. A. Chin, V. Prabhakaran, B. B. Bendlin, B. R. Postle, H. H. Goldsmith, C. M. Carlsson, M. A. Brooks, N. H. Kalin, L. E. Williams, H. A. Rowley
Summary: This study investigated 16,400 brain MRIs and found that incidental findings are common, ranging from trivial to life-threatening. Formal neuroradiologist interpretation yielded more reliable results compared to spontaneous detection by nonradiology scanning staff.
AMERICAN JOURNAL OF NEURORADIOLOGY
(2023)
Article
Neurosciences
Stephan A. Muller, Merav D. Shmueli, Xiao Feng, Johanna Tushaus, Neele Schumacher, Ryan Clark, Brad E. Smith, An Chi, Stefan Rose-John, Matthew E. Kennedy, Stefan F. Lichtenthaler
Summary: In this study, the researchers identified SEZ6 and gp130/IL6ST as physiological substrates of BACE1 in non-human-primate cerebrospinal fluid. They also found a reduction of gp130 in human CSF from a clinical trial with a BACE inhibitor and in plasma of BACE1-deficient mice. These findings provide insights into the relationship between BACE1 and gp130 in neuronal signaling and survival.
MOLECULAR NEURODEGENERATION
(2023)
Article
Neurosciences
Kyle J. Edmunds, Ira Driscoll, Erika W. Hagen, Jodi H. Barnet, Laurel A. Ravelo, David T. Plante, Julian M. Gaitan, Sarah R. Lose, Alice Motovylyak, Barbara B. Bendlin, Ozioma C. Okonkwo, Paul E. Peppard
Summary: This study provides new evidence for the protective role of cardiorespiratory fitness against the deleterious effects of obstructive sleep apnea (OSA) on brain aging.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Clinical Neurology
Rigina L. Gallagher, Rebecca Langhough Koscik, Jason F. Moody, Nicholas M. Vogt, Nagesh Adluru, Steven R. Kecskemeti, Carol A. Van Hulle, Nathaniel A. Chin, Sanjay Asthana, Gwendlyn Kollmorgen, Ivonne Suridjan, Cynthia M. Carlsson, Sterling C. Johnson, Douglas C. Dean III, Henrik Zetterberg, Kaj Blennow, Andrew L. Alexander, Barbara B. Bendlin
Summary: This study demonstrates that neurodegeneration-related markers can be detected among cognitively unimpaired individuals, and that these markers can capture early Alzheimer's disease pathology in individuals who are positive for A/T biomarkers but have normal cognitive function.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Clinical Neurology
Colin Denis, Kevin Dabbs, Veena A. Nair, Jedidiah Mathis, Dace N. Almane, Akshayaa Lakshmanan, Andrew Nencka, Rasmus M. Birn, Lisa Conant, Colin Humphries, Elizabeth Felton, Manoj Raghavan, Edgar A. Deyoe, Jeffrey R. Binder, Bruce Hermann, Vivek Prabhakaran, Barbara B. Bendlin, Mary E. Meyerand, Melanie Boly, Aaron F. Struck
Summary: There were no significant differences in myelin content between patients with temporal lobe epilepsy and the control group.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Article
Geriatrics & Gerontology
Adam R. Konopka, Dudley W. Lamming
Summary: Rapamycin, an inhibitor of mTORC1, has been shown to extend lifespan and prevent age-related diseases in various model systems. However, concerns over its side effects have limited its translation to humans. Studies suggest that the negative effects of rapamycin are associated with off-target inhibition of mTORC2. Therapeutic windows and alternatives to rapamycin are being explored to achieve more selective inhibition of mTORC1. Ongoing clinical trials aim to address safety, pharmacokinetics, pharmacodynamics, and efficacy of rapamycin and its analogs, providing important information for future phase 3 trials.
Article
Geriatrics & Gerontology
Madeline R. Hale, Rebecca Langhough, Lianlian Du, Bruce P. Hermann, Carol A. Van Hulle, Margherita Carboni, Gwendlyn Kollmorgenj, Kristin E. Basche, Davide Bruno, Leah Sanson-Miles, Erin M. Jonaitis, Nathaniel A. Chin, Ozioma C. Okonkwo, Barbara B. Bendlin, Cynthia M. Carlsson, Henrik Zetterberg, Kaj Blennow, Tobey J. Betthauser, Sterling C. Johnson, Kimberly D. Mueller
Summary: This study demonstrates a relationship between cerebrospinal fluid biomarkers and the ability to recall proper names in the preclinical phase of Alzheimer's disease.
NEUROBIOLOGY OF AGING
(2024)
Article
Clinical Neurology
Pontus Erickson, Joel Simren, Wagner S. Brum, Gilda E. Ennis, Gwendlyn Kollmorgen, Ivonne Suridjan, Rebecca Langhough, Erin M. Jonaitis, Carol A. Van Hulle, Tobey J. Betthauser, Cynthia M. Carlsson, Sanjay Asthana, Nicholas J. Ashton, Sterling C. Johnson, Leslie M. Shaw, Kaj Blennow, Ulf Andreasson, Barbara B. Bendlin, Henrik Zetterberg
Summary: The study aims to estimate the prevalence of CSF A-T+ biomarker profile and investigate its clinical implications. The results suggest that A-T+ biomarker profile is found in approximately 5% of lumbar punctures and is not associated with a higher rate of cognitive decline or biomarker signs of disease progression compared with biomarker-negative individuals.