Chronic elevation of plasma vascular endothelial growth factor-A (VEGF-A) is associated with a history of blast exposure

• Published in: Journal of the neurological sciences Vol. 417; p. 117049
• Main Authors: Meabon, James S., Cook, David G., Yagi, Mayumi, Terry, Garth E., Cross, Donna J., Muzi, Mark, Pagulayan, Kathleen F., Logsdon, Aric F., Schindler, Abigail G., Ghai, Vikas, Wang, Kai, Fallen, Shannon, Zhou, Yong, Kim, Taek-Kyun, Lee, Inyoul, Banks, William A., Carlson, Erik S., Mayer, Cynthia, Hendrickson, Rebecca C., Raskind, Murray A., Marshall, Desiree A., Perl, Daniel P., Keene, C. Dirk, Peskind, Elaine R.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.10.2020
• Subjects: 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; 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
• ISSN: 0022-510X; 1878-5883; 1878-5883
• DOI: 10.1016/j.jns.2020.117049

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.