Neuron, Volume 103, 7 August 2019,
Traumatic brain injury (TBI) is one the most common human afflictions, contributing to long-term disability in survivors. Emerging data indicate that functional improvement or deterioration can occur years after TBI. In this regard, TBI is recognized as risk factor for late-life neurodegenerative disorders. TBI encompasses a heterogeneous disease process in which diverse injury subtypes and multiple molecular mechanisms overlap. To develop precision medicine approaches where specific pathobiological processes are targeted by mechanistically appropriate therapies, techniques to identify and measure these subtypes are needed. Traumatic microvascular injury is a common but relatively understudied TBI endophenotype. In this review, we describe evidence of microvascular dysfunction in human and animal TBI, explore the role of vascular dysfunction in neurodegenerative disease, and discuss potential opportunities for vascular-directed therapies in ameliorating TBI-related neurodegeneration. We discuss the therapeutic potential of vascular-directed therapies in TBI and the use and limitations of preclinical models to explore these therapies. Sandsmark et al. review the evidence of microvascular dysfunction in human and animal TBI, explore the role of vascular dysfunction in neurodegenerative disease, and discuss the potential for vascular-directed therapies in ameliorating TBI-related neurodegeneration.
Acetylsalicylic Acid; Alzheimer Disease; Alzheimer's Disease; Amyloid Plaque; Animal; Animal Model; Animals; Arterial Spin Labeling; Biomarker; Blood Brain Barrier; Blood Vessel Tone; Blood-brain Barrier; Brain Blood Flow; Brain Circulation; Brain Concussion; Brain Injuries, Traumatic; Brain Ischemia; Brain Microcirculation; Cerebrovascular Circulation; Cerebrovascular Disease; Cerebrovasculature; Chronic Traumatic Encephalopathy; Complication; Degenerative Disease; Disease Exacerbation; Disease Progression; Endophenotype; Endothelial Dysfunction; Endothelium, Vascular; Fibrinolytic Agent; Human; Humans; Lithium; Metabolism; Microcirculation; Micronutrients; Microvasculature; Microvessels; Models, Animal; Mood Disorder; Multiinfarct Dementia; Nerve Degeneration; Nerve Protein; Nerve Tissue Proteins; Neurodegenerative Disease; Neurodegenerative Diseases; Neurofibrillary Tangle; Neuroimaging; Neurovascular Coupling; Neurovascular Unit; Nonhuman; Nonsteroid Antiinflammatory Agent; Pathology; Pathophysiology; Personalized Medicine; Priority Journal; Review; Seizure; Sildenafil; Sunitinib; Trace Element; Traumatic Brain Injury; Valproic Acid; Vascular Endothelium; Global