Exploring blood-brain barrier hyperpermeability and potential biomarkers in traumatic brain injury

Abstract

Blood-brain barrier breakdown and associated vascular hyperpermeability leads to vasogenic edema in traumatic brain injury (TBI). Tight junctions maintain blood-brain barrier integrity; their disruption in TBI holds significant promise for diagnosis and treatment. A controlled cortical impactor was used for TBI in mouse studies. Blood was collected 1 h after injury and sent for antibody microarray analysis. Twenty human subjects with radiographic evidence of TBI were enrolled and blood collected within 48 h of admission. Control subjects were individuals with nontrauma diagnoses. The subjects were matched by age and gender. Enzyme-linked immunosorbent assays were performed on each TBI and control sample for tight junction-associated proteins (TJPs), inflammatory markers, and S100b. Plasma was used to conduct in vitro monolayer permeability studies with human brain endothelial cells. S100b and the TJP occludin were significantly elevated in TBI plasma in both the murine and human studies. Monolayer permeability studies showed increased hyperpermeability in TBI groups. Plasma from TBI subjects increases microvascular hyperpermeability in vitro. TJPs in the blood may be a potential biomarker for TBI.

Blood-Brain Barrier Disintegration in Growth-Restricted Fetuses with Brain Sparing Effect

“…The brain endothelial function has an important role in many neurological diseases but there are no diagnostic tools to examine the fetal blood-brain barrier in clinical practice [ 44 ]. The TJPs that form the blood-brain barrier gave a promise as biomarkers in adults, and in animal models of brain injury [ 45 , 46 ], and may be tested as potential factors of fetal neuronal damage in prenatal life. Andersson et al observed the time-dependent changes of the CLN5 and OCLN concentrations in the blood and cerebrospinal fluid after a hypoxic brain damage in neonatal rats.…”

Targeting the Cerebrovascular System: Next-Generation Biomarkers and Treatment for Mild Traumatic Brain Injury

“…Plasma occludin levels were significantly elevated acutely after mTBI in humans when compared with uninjured controls; however, levels were also elevated in orthopedic injury controls (Shan and others 2016). Acutely elevated plasma occludin was also recently observed after mTBI in mice (Robinson and others 2020). To the best of our knowledge, no studies have assessed how blood occludin levels align with the extent of BBB damage after mTBI, although a recent study on ischemic stroke in rats revealed a strong correlation between acute serum occludin levels and BBB integrity as indicated by Evans blue extravasation (Pan and others 2017).…”

Role of microglia after subarachnoid hemorrhage

“…7,66 The accumulation of high-solute extracellular fluid from plasma protein leak into the brain secondary to a diminished ability of the BBB to exclude these molecules generates osmotic forces, increasing the overall volume of water within the brain. 67,68 Microglia can worsen vasogenic edema directly through their gene products. Vascular endothelial growth factor (VEGF) is upregulated following SAH in response to diminished baseline degradation of Hypoxia-inducible factor 1 (HIF-1).…”