Oxygen-Glucose Deprivation/Reoxygenation Induces Human Brain Microvascular Endothelial Cell Hyperpermeability Via VE-Cadherin Internalization: Roles of RhoA/ROCK2

Blood-Brain Barrier: More Contributor to Disruption of Central Nervous System Homeostasis Than Victim in Neurological Disorders

“…VE-cadherin is important for AJ assembly and BBB regulation ( Li et al, 2018 ). In conditions of oxygen-glucose deprivation (OGD), VE-cadherin internalization induces BBB hyperpermeability via the RhoA/ROCK2 pathway ( Chen J. et al, 2019 ). VE-cadherin phosphorylation under pathological conditions results in uncoupling of ECs and increased vascular permeability; thus, it may also serve as a novel target in moderating BBB dysfunction ( Li et al, 2018 ).…”

Modeling blood–brain barrier pathology in cerebrovascular disease in vitro: current and future paradigms

“…Similar to OGD, the degree of injury after reperfusion varies with time of the exposure of cells to normoxia and normalized glucose level. This experimental setting has been applied in numerus studies with 2-D BBB models in both monocultures of BECs and dual and triple co-cultures of murine and human primary and immortalized cell lines [96,[159][160][161][162][163][164][165][166][167][168]. However, in addition to reducing oxygen and glucose delivery, stroke in vivo also reduces blood flow and thereby endothelial shear stress.…”

“…Thus, there is hyperpermeability, inflammation, focal excitotoxicity/cytotoxicity and alterations in transporter expression and function. The degree of diminished BBB integrity can be evaluated by measuring TEER and/or tracer permeability (ranging from small to high molecular weight) at different time points of OGD and reperfusion [96,160,163,168,172]. TEER assesses ionic permeability and it has limitations in defining the degree of BBB hyperpermeability.…”

“…Summary of current in vitro models of CVD that include the modeled in vitro condition, blood brain barrier (BBB) pathology and utilized in vitro BBB model CVD In vitro model condition BBB pathology Utilized in vitro BBB model Refs. Stroke Ischemic OGD (1–5 h) OGD + Reperfusion (reoxygenation + normal glucose level) (1–5 h + 1–96 h) Chemical ischemia ( rotenone, antimycin and sodium azide ) Enzymatic ( GOX, GOX/CAT and 2 - deoxyglucose ) Hyperpermeability Cytotoxicity Inflammation BBB recovery Angiogenesis BEC monolayer 2-D model DIV-BBB 3-D model [ 78 , 127 , 148 , 160 , 162 , 165 ] [ 164 , 166 , 167 , 182 ] [ 126 ] [ 135 ] [ 156 – 158 ] Hemorrhagic hemin/hemoglobin +/OGD thrombin ± OGD Hyperpermeability Cytotoxicity Inflammation BEC monolayer 2-D model [ 187 , 189 , 207 – 211 ] [ 186 ] Vascular dementia CADASIL Replicative senescence H 2 O 2 (50 μM) modification of telomerase DNA damage NOTCH3 mutation Senescence Hyperpermeability Inflammation BEC monolayer hiPSC [ 194 , …”

Non-Mitogenic Fibroblast Growth Factor 1 Enhanced Angiogenesis Following Ischemic Stroke by Regulating the Sphingosine-1-Phosphate 1 Pathway

“…Control group is the HBMECs monolayers culture without OGD/R treatment. For the OGD/R treatment, the protocol was performed as described previously (Lin et al, 2018;Chen et al, 2019b). In brief, HBMECs cultured EBM-2 media were replaced with glucose free DMEM media, and then the cells cultured dish or plates were put in a specialized, humidified chamber (Heidolph, incubator 1000, Brinkmann Instruments, Westbury, NY) at 37°C, which contained an anaerobic gas mixture (90% N 2 , 5% H 2 , and 5% CO 2 ), for 20 minutes to ensure anaerobic conditions, and for a further 4 hours incubation.…”