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4. Agrin expression during synaptogenesis induced by traumatic brain injury

Author

M. Cristina Falo, Thomas M. Reeves, and Linda L. Phillips

Subjects
Male, animal structures, Synaptogenesis, Presynaptic Terminals, Biology, Receptors, N-Methyl-D-Aspartate, Lesion, Extracellular matrix, Rats, Sprague-Dawley, Neuroplasticity, medicine, Animals, Entorhinal Cortex, Agrin, RNA, Messenger, Neuronal Plasticity, Entorhinal cortex, Denervation, Original Papers, Cell biology, Extracellular Matrix, Nerve Regeneration, Rats, Up-Regulation, Disease Models, Animal, Neuroprotective Agents, nervous system, Gene Expression Regulation, Brain Injuries, Synaptic plasticity, NMDA receptor, Matrix Metalloproteinase 3, Neurology (clinical), medicine.symptom, Dizocilpine Maleate, Neuroscience, Excitatory Amino Acid Antagonists
Abstract

Interaction between extracellular matrix proteins and regulatory proteinases can mediate synaptic integrity. Previously, we documented that matrix metalloproteinase 3 (MMP-3) expression and activity increase following traumatic brain injury (TBI). We now report protein and mRNA analysis of agrin, a MMP-3 substrate, over the time course of trauma-induced synaptogenesis. Agrin expression during the successful synaptic reorganization of unilateral entorhinal cortical lesion (UEC) was compared with expression when normal synaptogenesis fails (combined fluid percussion TBI and bilateral entorhinal lesion [BEC]). We observed that agrin protein was increased in both models at 2 and 7 days postinjury, and immuohistochemical (IHC) co-localization suggested reactive astrocytes contribute to that increase. Agrin formed defined boundaries for sprouting axons along deafferented dendrites in the UEC, but failed to do so after combined insult. Similarly, Western blot analysis revealed greater increase in UEC agrin protein relative to the combined TBI+BEC model. Both models showed increased agrin transcription at 7 days postinjury and mRNA normalization by 15 days. Attenuation of synaptic pathology with the NMDA antagonist MK-801 reduced 7-day UEC agrin transcript to a level not different from unlesioned controls. By contrast, MK-801 in the combined insult failed to significantly change 7-day agrin transcript, mRNA levels remaining elevated over uninjured sham cases. Together, these results suggest that agrin plays an important role in the sprouting phase of reactive synaptogenesis, and that both its expression and distribution are correlated with extent of successful recovery after TBI. Further, when pathogenic conditions which induce synaptic plasticity are reduced, increase in agrin mRNA is attenuated.

Published
2008

12. A Systematic Review of Positron Emission Tomography of Tau, Amyloid Beta, and Neuroinflammation in Chronic Traumatic Encephalopathy: The Evidence To Date

Author

Lee, Bern G, Leavitt, MacKenzie J, Bernick, Charles B, Leger, Gabriel C, Rabinovici, Gil, and Banks, Sarah J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Brain Disorders, Biomedical Imaging, Neurosciences, Neurodegenerative, Acquired Cognitive Impairment, Traumatic Brain Injury (TBI), Neurological, Amyloid Neuropathies, Amyloid beta-Peptides, Brain, Chronic Traumatic Encephalopathy, Craniocerebral Trauma, Evidence-Based Medicine, Humans, Inflammation, Positron-Emission Tomography, Tauopathies, tau Proteins, adult brain injury, beta amyloid, head trauma, inflammation, PET scanning, Neurology & Neurosurgery, Clinical sciences, Biological psychology
Abstract

Chronic traumatic encephalopathy (CTE) is associated with pathological changes, yet detecting these changes during life has proven elusive. Positron emission tomography (PET) offers the potential for identifying such pathology. Few studies have been completed to date and their approaches and results have been diverse. It was the objective of this review to systematically examine relevant research using ligands for PET that bind to identified pathology in CTE. We focused on identification of patterns of binding and addressing gaps in knowledge of PET imaging for CTE. A comprehensive literature search was conducted. Data used were published on or before May 22, 2017. As the extant literature is limited, any peer-reviewed article assessing military, contact sports athletes, or professional fighters was considered for inclusion. The main outcomes were regional binding to brain regions identified through control comparisons or through clinical metrics (e.g., standardized uptake volume ratios). A total of 1207 papers were identified for review, of which six met inclusion criteria. Meta-analyses were planned but were deemed inappropriate given the small number of studies identified. Methodological concerns in these initial papers included small sample sizes, lack of a control comparison, use of nonstandard statistical procedures to quantify data, and interpretation of potentially off-target binding areas. Across studies, the hippocampi, amygdalae, and midbrain had reasonably consistent increased uptake. Evidence for increased uptake in cortical regions was less consistent. The evidence suggests that the field of PET imaging in those at risk for CTE remains nascent. As the field evolves to include more stringent studies, ligands for PET may prove an important tool in identifying CTE in vivo.

Published
2018

13. International Spinal Cord Injury Biobank: A Biorepository and Resource for Translational Research.

Author

Hirsch-Reinshagen, Veronica, Velenosi, Adam, Morris, Sarah R., Dong, Kevin, Samadi-Bahrami, Zahra, Nassimbwa, Sureyah, Abdelaziz, Eslam, Kozlowski, Piotr, Moore, G.R. Wayne, Laule, Cornelia, and Kwon, Brian K.

Subjects
*SPINAL cord injuries, *TRANSLATIONAL research, *DISABILITIES, *STANDARD operating procedure
Abstract

Over the past few decades, tremendous advances have been made in our understanding of the biological changes underpinning the devastating impairment of traumatic spinal cord injury (SCI). Much of this scientific research has focused on animal models of SCI, and comparatively little has been done in human SCI, largely because biospecimens from human SCI patients are not readily available. This paucity of scientific enquiry in human SCI represents an important void in the spectrum of translational research, as biological differences between animal models and the human condition need to be considered in the pre-clinical development of therapeutic approaches. The International Spinal Cord Injury Biobank (ISCIB) is a multi-user biorepository with the mission of accelerating therapeutic development in traumatic SCI through improved biological understanding of human injury, and the vision of serving as a global research resource where human SCI biospecimens are shared with researchers around the world. Aligned with internationally recognized best practices, ISCIB's formal governance structure and standard operating procedures have earned it official biobank certification through the Canadian Tissue Repository Network. Herein, we describe the translational research gap that ISCIB is helping to fill; its structure, governance and certification; how data and samples are accrued, processed and stored; and finally, the process through which samples and data are shared with global researchers. The purpose of this paper describing ISCIB is to serve as an introductory guidance document for the wider community of SCI researchers. By helping researchers understand the contents of ISCIB and the process of accessing biospecimens, we seek to further ISCIB's vision as being a resource for human and translational research in SCI, with the ultimate goal of finding disease-modifying therapies for this disabling condition. [ABSTRACT FROM AUTHOR]

Published
2022
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15. Imaging Findings in Acute Traumatic Brain Injury: a National Institute of Neurological Disorders and Stroke Common Data Element-Based Pictorial Review and Analysis of Over 4000 Admission Brain Computed Tomography Scans from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study

Author

Vande Vyvere, Thijs, Pisică, Dana, Wilms, Guido, Claes, Lene, Van Dyck, Pieter, Snoeckx, Annemiek, van den Hauwe, Luc, Pullens, Pim, Verheyden, Jan, Wintermark, Max, Dekeyzer, Sven, Mac Donald, Christine L., Maas, Andrew I.R., and Parizel, Paul M.

Published
2024
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23. A Four-Country Study of Strangulation-Related Alterations in Consciousness in Women Who Have Experienced Intimate Partner Violence: Co-Occurrence with Traumatic Brain Injuries and Measures of Psychological Distress.

Author

Adhikari, Shambhu Prasad, Daugherty, Julia C., Quiroz Molinares, Nathalia, Maldonado-Rodriguez, Naomi, Wallace, Colin, Smirl, Jonathan, Perez-García, Miguel, De los Reyes-Aragón, Carlos José, Hidalgo-Ruzzante, Natalia, van Donkelaar, Paul, and Valera, Eve M.

Published
2024
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37. Examining the Subacute Effects of Mild Traumatic Brain Injury Using a Traditional and Computerized Neuropsychological Test Battery.

Author

Karlsen, Rune Hatlestad, Saksvik, Simen Berg, Stenberg, Jonas, Lundervold, Astri Johansen, Olsen, Alexander, Rautio, Ida, Folvik, Line, Håberg, Asta Kristine, Vik, Anne, Karr, Justin E., Iverson, Grant L., and Skandsen, Toril

Subjects
*BRAIN injuries, *NEUROPSYCHOLOGICAL tests, *TRAUMA centers, *LOSS of consciousness, *ELECTRIC batteries
Abstract

This study investigates subacute cognitive effects of mild traumatic brain injury (MTBI) in the Trondheim Mild TBI Study, as measured, in part, by the neuropsychological test battery of the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) program, including computerized tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and traditional paper-and-pencil tests. We investigated whether cognitive function was associated with injury severity: intracranial traumatic lesions on neuroimaging, witnessed loss of consciousness (LOC), or post-traumatic amnesia (PTA) >1 h. Further, we explored which of the tests in the CENTER-TBI battery might be associated with the largest subacute effects of MTBI (i.e., at 2 weeks post-injury). We recruited 177 patients with MTBI (16–59 years of age) from a regional trauma center and an outpatient clinic,79 trauma control participants, and 81 community control participants. The MTBI group differed from community controls only on one traditional test of processing speed (coding; p = 0.009, Cliff's delta [Δ] = 0.20). Patients with intracranial abnormalities performed worse than those without on a traditional test (phonemic verbal fluency; p = 0.043, Δ = 0.27), and patients with LOC performed differently on the Attention Switching Task from the CANTAB (p = 0.020, Δ = −0.20). Patients with PTA >1 h performed worse than those with <1 h on 10 measures, from traditional tests and the CANTAB (Δ = 0.33–0.20), likely attributable, at least in part, to pre-existing differences in intellectual functioning between groups. In general, those with MTBI had good neuropsychological outcome 2 weeks after injury and no particular CENTER-TBI computerized or traditional tests seemed to be more sensitive to subtle cognitive deficits. [ABSTRACT FROM AUTHOR]

Published
2021
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42. Metabotropic Glutamate Receptor 2 Expression Is Chronically Elevated in Male Rats With Post-Traumatic Stress Disorder Related Behavioral Traits Following Repetitive Low-Level Blast Exposure.

Author

De Gasperi, Rita, Gama Sosa, Miguel A., Perez Garcia, Georgina, Perez, Gissel M., Pryor, Dylan, Morrison, Chenel L-A., Lind, Rachel, Abutarboush, Rania, Kawoos, Usmah, Statz, Jonathan K., Patterson, Jacob, Hof, Patrick R., Zhu, Carolyn W., Ahlers, Stephen T., Cook, David G., and Elder, Gregory A.

Published
2024
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49. CARE4Kids Study: Endophenotypes of Persistent Post-Concussive Symptoms in Adolescents: Study Rationale and Protocol.

Author

Giza, Christopher C., Gioia, Gerard, Cook, Lawrence J., Asarnow, Robert, Snyder, Aliyah, Babikian, Talin, Thompson, Paul, Bazarian, Jeffery J., Whitlow, Christopher T., Miles, Christopher M., Otallah, Scott, Kamins, Joshua, Didehbani, Nyaz, Rosenbaum, Philip E., Chrisman, Sara P.D., Vaughan, Christopher G., Cullum, Munro, Popoli, David M., Choe, Meeryo, and Gill, Jessica

Published
2024
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