Chronic elevation of plasma vascular endothelial growth factor-A (VEGF-A) is associated with a history of blast exposure
Mounting evidence points to the significance of neurovascular-related dysfunction in veterans with blast-related mTBI, which is also associated with reduced [18F]-fluorodeoxyglucose (FDG) uptake. The goal of this study was to determine whether plasma VEGF-A is altered in veterans with blast-related...
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| Published in | Journal of the neurological sciences Vol. 417; p. 117049 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier B.V
15.10.2020
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| Online Access | Get full text |
| ISSN | 0022-510X 1878-5883 1878-5883 |
| DOI | 10.1016/j.jns.2020.117049 |
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| Abstract | Mounting evidence points to the significance of neurovascular-related dysfunction in veterans with blast-related mTBI, which is also associated with reduced [18F]-fluorodeoxyglucose (FDG) uptake.
The goal of this study was to determine whether plasma VEGF-A is altered in veterans with blast-related mTBI and address whether VEGF-A levels correlate with FDG uptake in the cerebellum, a brain region that is vulnerable to blast-related injury 72 veterans with blast-related mTBI (mTBI) and 24 deployed control (DC) veterans with no lifetime history of TBI were studied. Plasma VEGF-A was significantly elevated in mTBIs compared to DCs. Plasma VEGF-A levels in mTBIs were significantly negatively correlated with FDG uptake in cerebellum. In addition, performance on a Stroop color/word interference task was inversely correlated with plasma VEGF-A levels in blast mTBI veterans. Finally, we observed aberrant perivascular VEGF-A immunoreactivity in postmortem cerebellar tissue and not cortical or hippocampal tissues from blast mTBI veterans.
These findings add to the limited number of plasma proteins that are chronically elevated in veterans with a history of blast exposure associated with mTBI. It is likely the elevated VEGF-A levels are from peripheral sources. Nonetheless, increasing plasma VEGF-A concentrations correlated with chronically decreased cerebellar glucose metabolism and poorer performance on tasks involving cognitive inhibition and set shifting. These results strengthen an emerging view that cognitive complaints and functional brain deficits caused by blast exposure are associated with chronic blood-brain barrier injury and prolonged recovery in affected regions.
•Plasma VEGF-A is chronically elevated in veterans with blast-related mTBI.•Plasma VEGF-A correlates with glucose uptake measured by FDG-PET in cerebellum.•Impaired cognitive inhibition correlates with plasma VEGF-A in blast mTBI veterans.•Chronic vascular disturbances are an important feature of blast-related mTBI. |
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| AbstractList | Mounting evidence points to the significance of neurovascular-related dysfunction in veterans with blast-related mTBI, which is also associated with reduced [18F]-fluorodeoxyglucose (FDG) uptake. The goal of this study was to determine whether plasma VEGF-A is altered in veterans with blast-related mTBI and address whether VEGF-A levels correlate with FDG uptake in the cerebellum, a brain region that is vulnerable to blast-related injury 72 veterans with blast-related mTBI (mTBI) and 24 deployed control (DC) veterans with no lifetime history of TBI were studied. Plasma VEGF-A was significantly elevated in mTBIs compared to DCs. Plasma VEGF-A levels in mTBIs were significantly negatively correlated with FDG uptake in cerebellum. In addition, performance on a Stroop color/word interference task was inversely correlated with plasma VEGF-A levels in blast mTBI veterans. Finally, we observed aberrant perivascular VEGF-A immunoreactivity in postmortem cerebellar tissue and not cortical or hippocampal tissues from blast mTBI veterans. These findings add to the limited number of plasma proteins that are chronically elevated in veterans with a history of blast exposure associated with mTBI. It is likely the elevated VEGF-A levels are from peripheral sources. Nonetheless, increasing plasma VEGF-A concentrations correlated with chronically decreased cerebellar glucose metabolism and poorer performance on tasks involving cognitive inhibition and set shifting. These results strengthen an emerging view that cognitive complaints and functional brain deficits caused by blast exposure are associated with chronic blood-brain barrier injury and prolonged recovery in affected regions.Mounting evidence points to the significance of neurovascular-related dysfunction in veterans with blast-related mTBI, which is also associated with reduced [18F]-fluorodeoxyglucose (FDG) uptake. The goal of this study was to determine whether plasma VEGF-A is altered in veterans with blast-related mTBI and address whether VEGF-A levels correlate with FDG uptake in the cerebellum, a brain region that is vulnerable to blast-related injury 72 veterans with blast-related mTBI (mTBI) and 24 deployed control (DC) veterans with no lifetime history of TBI were studied. Plasma VEGF-A was significantly elevated in mTBIs compared to DCs. Plasma VEGF-A levels in mTBIs were significantly negatively correlated with FDG uptake in cerebellum. In addition, performance on a Stroop color/word interference task was inversely correlated with plasma VEGF-A levels in blast mTBI veterans. Finally, we observed aberrant perivascular VEGF-A immunoreactivity in postmortem cerebellar tissue and not cortical or hippocampal tissues from blast mTBI veterans. These findings add to the limited number of plasma proteins that are chronically elevated in veterans with a history of blast exposure associated with mTBI. It is likely the elevated VEGF-A levels are from peripheral sources. Nonetheless, increasing plasma VEGF-A concentrations correlated with chronically decreased cerebellar glucose metabolism and poorer performance on tasks involving cognitive inhibition and set shifting. These results strengthen an emerging view that cognitive complaints and functional brain deficits caused by blast exposure are associated with chronic blood-brain barrier injury and prolonged recovery in affected regions. Mounting evidence points to the significance of neurovascular-related dysfunction in veterans with blast-related mTBI, which is also associated with reduced [18F]-fluorodeoxyglucose (FDG) uptake. The goal of this study was to determine whether plasma VEGF-A is altered in veterans with blast-related mTBI and address whether VEGF-A levels correlate with FDG uptake in the cerebellum, a brain region that is vulnerable to blast-related injury 72 veterans with blast-related mTBI (mTBI) and 24 deployed control (DC) veterans with no lifetime history of TBI were studied. Plasma VEGF-A was significantly elevated in mTBIs compared to DCs. Plasma VEGF-A levels in mTBIs were significantly negatively correlated with FDG uptake in cerebellum. In addition, performance on a Stroop color/word interference task was inversely correlated with plasma VEGF-A levels in blast mTBI veterans. Finally, we observed aberrant perivascular VEGF-A immunoreactivity in postmortem cerebellar tissue and not cortical or hippocampal tissues from blast mTBI veterans. These findings add to the limited number of plasma proteins that are chronically elevated in veterans with a history of blast exposure associated with mTBI. It is likely the elevated VEGF-A levels are from peripheral sources. Nonetheless, increasing plasma VEGF-A concentrations correlated with chronically decreased cerebellar glucose metabolism and poorer performance on tasks involving cognitive inhibition and set shifting. These results strengthen an emerging view that cognitive complaints and functional brain deficits caused by blast exposure are associated with chronic blood-brain barrier injury and prolonged recovery in affected regions. •Plasma VEGF-A is chronically elevated in veterans with blast-related mTBI.•Plasma VEGF-A correlates with glucose uptake measured by FDG-PET in cerebellum.•Impaired cognitive inhibition correlates with plasma VEGF-A in blast mTBI veterans.•Chronic vascular disturbances are an important feature of blast-related mTBI. Mounting evidence points to the significance of neurovascular-related dysfunction in veterans with blast-related mTBI, which is also associated with reduced [ 18 F]-fluorodeoxyglucose (FDG) uptake. The goal of this study was to determine whether plasma VEGF-A is altered in veterans with blast-related mTBI and address whether VEGF-A levels correlate with FDG uptake in the cerebellum, a brain region that is vulnerable to blast-related injury 72 veterans with blast-related mTBI (mTBI) and 24 deployed control (DC) veterans with no lifetime history of TBI were studied. Plasma VEGF-A was significantly elevated in mTBIs compared to DCs. Plasma VEGF-A levels in mTBIs were significantly negatively correlated with FDG uptake in cerebellum. In addition, performance on a Stroop color/word interference task was inversely correlated with plasma VEGF-A levels in blast mTBI veterans. Finally, we observed aberrant perivascular VEGF-A immunoreactivity in postmortem cerebellar tissue and not cortical or hippocampal tissues from blast mTBI veterans. These findings add to the limited number of plasma proteins that are chronically elevated in veterans with a history of blast exposure associated with mTBI. It is likely the elevated VEGF-A levels are from peripheral sources. Nonetheless, increasing plasma VEGF-A concentrations correlated with chronically decreased cerebellar glucose metabolism and poorer performance on tasks involving cognitive inhibition and set shifting. These results strengthen an emerging view that cognitive complaints and functional brain deficits caused by blast exposure are associated with chronic blood-brain barrier injury and prolonged recovery in affected regions. AbstractMounting evidence points to the significance of neurovascular-related dysfunction in veterans with blast-related mTBI, which is also associated with reduced [ 18F]-fluorodeoxyglucose (FDG) uptake. The goal of this study was to determine whether plasma VEGF-A is altered in veterans with blast-related mTBI and address whether VEGF-A levels correlate with FDG uptake in the cerebellum, a brain region that is vulnerable to blast-related injury. 72 veterans with blast-related mTBI (mTBI) and 24 deployed control (DC) veterans with no lifetime history of TBI were studied. Plasma VEGF-A was significantly elevated in mTBIs compared to DCs. Plasma VEGF-A levels in mTBIs were significantly negatively correlated with FDG uptake in cerebellum. In addition, performance on a Stroop color/word interference task was inversely correlated with plasma VEGF-A levels in blast mTBI veterans. Finally, we observed aberrant perivascular VEGF-A immunoreactivity in postmortem cerebellar tissue and not cortical or hippocampal tissues from blast mTBI veterans. These findings add to the limited number of plasma proteins that are chronically elevated in veterans with a history of blast exposure associated with mTBI. It is likely the elevated VEGF-A levels are from peripheral sources. Nonetheless, increasing plasma VEGF-A concentrations correlated with chronically decreased cerebellar glucose metabolism and poorer performance on tasks involving cognitive inhibition and set shifting. These results strengthen an emerging view that cognitive complaints and functional brain deficits caused by blast exposure are associated with chronic blood-brain barrier injury and prolonged recovery in affected regions. Mounting evidence points to the significance of neurovascular-related dysfunction in veterans with blast-related mTBI, which is also associated with reduced [ F]-fluorodeoxyglucose (FDG) uptake. The goal of this study was to determine whether plasma VEGF-A is altered in veterans with blast-related mTBI and address whether VEGF-A levels correlate with FDG uptake in the cerebellum, a brain region that is vulnerable to blast-related injury 72 veterans with blast-related mTBI (mTBI) and 24 deployed control (DC) veterans with no lifetime history of TBI were studied. Plasma VEGF-A was significantly elevated in mTBIs compared to DCs. Plasma VEGF-A levels in mTBIs were significantly negatively correlated with FDG uptake in cerebellum. In addition, performance on a Stroop color/word interference task was inversely correlated with plasma VEGF-A levels in blast mTBI veterans. Finally, we observed aberrant perivascular VEGF-A immunoreactivity in postmortem cerebellar tissue and not cortical or hippocampal tissues from blast mTBI veterans. These findings add to the limited number of plasma proteins that are chronically elevated in veterans with a history of blast exposure associated with mTBI. It is likely the elevated VEGF-A levels are from peripheral sources. Nonetheless, increasing plasma VEGF-A concentrations correlated with chronically decreased cerebellar glucose metabolism and poorer performance on tasks involving cognitive inhibition and set shifting. These results strengthen an emerging view that cognitive complaints and functional brain deficits caused by blast exposure are associated with chronic blood-brain barrier injury and prolonged recovery in affected regions. |
| ArticleNumber | 117049 |
| Author | Muzi, Mark Lee, Inyoul Peskind, Elaine R. Carlson, Erik S. Cross, Donna J. Fallen, Shannon Ghai, Vikas Cook, David G. Zhou, Yong Marshall, Desiree A. Perl, Daniel P. Meabon, James S. Keene, C. Dirk Yagi, Mayumi Logsdon, Aric F. Mayer, Cynthia Raskind, Murray A. Kim, Taek-Kyun Banks, William A. Schindler, Abigail G. Pagulayan, Kathleen F. Wang, Kai Terry, Garth E. Hendrickson, Rebecca C. |
| AuthorAffiliation | a Veterans Affairs (VA) Northwest Mental Illness, Research, Education, and Clinical Center (MIRECC), Seattle, WA, USA g Department of Radiology, University of Washington, Seattle, WA, USA d Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington, Seattle, WA, USA f Department of Radiology, University of Utah, Salt Lake City, UT, USA j Department of Pathology, Center for Neuroscience and Regenerative Medicine, School of Medicine, Uniformed Services University, Bethesda, MD, USA c Geriatric Research, Education, and Clinical Center (GRECC), Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA h Institute for Systems Biology, Seattle, WA, USA e Department of Pharmacology, University of Washington, Seattle, WA, USA b Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA i Department of Pathology, University of Washington, Seattle, WA, USA |
| AuthorAffiliation_xml | – name: g Department of Radiology, University of Washington, Seattle, WA, USA – name: d Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington, Seattle, WA, USA – name: e Department of Pharmacology, University of Washington, Seattle, WA, USA – name: i Department of Pathology, University of Washington, Seattle, WA, USA – name: j Department of Pathology, Center for Neuroscience and Regenerative Medicine, School of Medicine, Uniformed Services University, Bethesda, MD, USA – name: f Department of Radiology, University of Utah, Salt Lake City, UT, USA – name: b Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA – name: a Veterans Affairs (VA) Northwest Mental Illness, Research, Education, and Clinical Center (MIRECC), Seattle, WA, USA – name: c Geriatric Research, Education, and Clinical Center (GRECC), Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA – name: h Institute for Systems Biology, Seattle, WA, USA |
| Author_xml | – sequence: 1 givenname: James S. surname: Meabon fullname: Meabon, James S. organization: Veterans Affairs (VA) Northwest Mental Illness, Research, Education, and Clinical Center (MIRECC), Seattle, WA, USA – sequence: 2 givenname: David G. surname: Cook fullname: Cook, David G. organization: Geriatric Research, Education, and Clinical Center (GRECC), Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA – sequence: 3 givenname: Mayumi surname: Yagi fullname: Yagi, Mayumi organization: Geriatric Research, Education, and Clinical Center (GRECC), Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA – sequence: 4 givenname: Garth E. surname: Terry fullname: Terry, Garth E. organization: Veterans Affairs (VA) Northwest Mental Illness, Research, Education, and Clinical Center (MIRECC), Seattle, WA, USA – sequence: 5 givenname: Donna J. surname: Cross fullname: Cross, Donna J. organization: Department of Radiology, University of Utah, Salt Lake City, UT, USA – sequence: 6 givenname: Mark surname: Muzi fullname: Muzi, Mark organization: Department of Radiology, University of Washington, Seattle, WA, USA – sequence: 7 givenname: Kathleen F. surname: Pagulayan fullname: Pagulayan, Kathleen F. organization: Veterans Affairs (VA) Northwest Mental Illness, Research, Education, and Clinical Center (MIRECC), Seattle, WA, USA – sequence: 8 givenname: Aric F. surname: Logsdon fullname: Logsdon, Aric F. organization: Geriatric Research, Education, and Clinical Center (GRECC), Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA – sequence: 9 givenname: Abigail G. surname: Schindler fullname: Schindler, Abigail G. organization: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA – sequence: 10 givenname: Vikas surname: Ghai fullname: Ghai, Vikas organization: Institute for Systems Biology, Seattle, WA, USA – sequence: 11 givenname: Kai surname: Wang fullname: Wang, Kai organization: Institute for Systems Biology, Seattle, WA, USA – sequence: 12 givenname: Shannon surname: Fallen fullname: Fallen, Shannon organization: Institute for Systems Biology, Seattle, WA, USA – sequence: 13 givenname: Yong surname: Zhou fullname: Zhou, Yong organization: Institute for Systems Biology, Seattle, WA, USA – sequence: 14 givenname: Taek-Kyun surname: Kim fullname: Kim, Taek-Kyun organization: Institute for Systems Biology, Seattle, WA, USA – sequence: 15 givenname: Inyoul surname: Lee fullname: Lee, Inyoul organization: Institute for Systems Biology, Seattle, WA, USA – sequence: 16 givenname: William A. surname: Banks fullname: Banks, William A. organization: Geriatric Research, Education, and Clinical Center (GRECC), Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA – sequence: 17 givenname: Erik S. surname: Carlson fullname: Carlson, Erik S. organization: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA – sequence: 18 givenname: Cynthia surname: Mayer fullname: Mayer, Cynthia organization: Veterans Affairs (VA) Northwest Mental Illness, Research, Education, and Clinical Center (MIRECC), Seattle, WA, USA – sequence: 19 givenname: Rebecca C. surname: Hendrickson fullname: Hendrickson, Rebecca C. organization: Veterans Affairs (VA) Northwest Mental Illness, Research, Education, and Clinical Center (MIRECC), Seattle, WA, USA – sequence: 20 givenname: Murray A. surname: Raskind fullname: Raskind, Murray A. organization: Veterans Affairs (VA) Northwest Mental Illness, Research, Education, and Clinical Center (MIRECC), Seattle, WA, USA – sequence: 21 givenname: Desiree A. surname: Marshall fullname: Marshall, Desiree A. organization: Department of Pathology, University of Washington, Seattle, WA, USA – sequence: 22 givenname: Daniel P. surname: Perl fullname: Perl, Daniel P. organization: Department of Pathology, Center for Neuroscience and Regenerative Medicine, School of Medicine, Uniformed Services University, Bethesda, MD, USA – sequence: 23 givenname: C. Dirk surname: Keene fullname: Keene, C. Dirk organization: Department of Pathology, University of Washington, Seattle, WA, USA – sequence: 24 givenname: Elaine R. surname: Peskind fullname: Peskind, Elaine R. email: peskind@uw.edu organization: Veterans Affairs (VA) Northwest Mental Illness, Research, Education, and Clinical Center (MIRECC), Seattle, WA, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32758764$$D View this record in MEDLINE/PubMed |
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| Keywords | DSM-IV BBB FDG CNS DKEFS PHQ-9 Angiogenic CSF Endothelial BRIEF-A Neurovascular Vascular VEGF-A bFGF Neurotrauma PTSD VOI CTE OEF/OIF IAS Neurovascular unit mTBI PET PSQI VA/DoD vascular endothelial growth factor-A volume of interest interface astroglial scarring Pittsburgh Sleep Quality Index Patient Health Questionaire-9 [ 18F]-fluorodeoxyglucose chronic traumatic encephalopathy basic fibroblast growth factor, FGF2 Diagnostic and Statistical Manual of Mental Disorders, 4th edition blood-brain barrier Operation Enduring Freedom/Operation Iraqi Freedom Veterans Affairs/Department of Defense mild traumatic brain injury central nervous system posttraumatic stress disorder Delis-Kaplan Executive Function Scale cerebrospinal fluid Behavioral Rating Inventory for Executive Function-Adult Version positron emission tomography |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Data collection and statistical analyses: Meabon, Peskind, Cook, Terry, Muzi, Yagi, Pagulayan, Mayer, Cross. Drafted manuscript: Cook, Peskind, Meabon. Clinical evaluation of research participants: Peskind, Pagulayan, Hendrickson, Mayer, Perl, Keene, Marshall, Raskind. Concept and design: Meabon, Peskind, Cook, Pagulayan, Carlson. Critical manuscript revisions for important intellectual content: Raskind, Logsdon, Schindler, Banks, Ghai, Wang, Fallen, Zhou, Kim, Lee, Terry, Cross, Carlson, Pagulayan. Author contributions |
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| Snippet | Mounting evidence points to the significance of neurovascular-related dysfunction in veterans with blast-related mTBI, which is also associated with reduced... AbstractMounting evidence points to the significance of neurovascular-related dysfunction in veterans with blast-related mTBI, which is also associated with... Mounting evidence points to the significance of neurovascular-related dysfunction in veterans with blast-related mTBI, which is also associated with reduced [... |
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| SubjectTerms | Angiogenic Blast Injuries - complications Blast Injuries - diagnostic imaging Brain Concussion Endothelial Humans Neurology Neurotrauma Neurovascular Neurovascular unit Stress Disorders, Post-Traumatic Vascular Vascular Endothelial Growth Factor A Veterans |
| Title | Chronic elevation of plasma vascular endothelial growth factor-A (VEGF-A) is associated with a history of blast exposure |
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