Erythrocytes, a New Contributor to Age‐Associated Loss of Blood–Brain Barrier Integrity

Abstract

Blood exchanges between young and old partners demonstrate old blood has a detrimental effect on brain health of young animals. Previous studies primarily investigate soluble blood factors, such as transforming growth factor-beta, on the brain and the blood-brain barrier (BBB). However, the role of blood cellular components, particularly erythrocytes, has not been defined. Erythrocyte morphology and rigidity change as mammals age, altering their transport within the capillary bed. This impacts downstream biological events, such as the release of reactive oxygen species and hemoglobin, potentially compromising the BBB. Here, a micro electrical BBB (μE-BBB), with cocultured endothelial and astrocytic cells, and a built-in trans-endothelial electrical resistance (TEER) system is described to monitor the effect of capillary shear stress on erythrocytes derived from young and old mice and people and the subsequent effects of these cells on BBB integrity. This is monitored by the passage of fluorescein isothiocyanate-dextran and real-time profiling of TEER across the BBB after old and young erythrocyte exposure. Compared to young erythrocytes, old erythrocytes induce an increased permeability by 42% and diminished TEER by 2.9% of the μE-BBB. These results suggest that changes in circulating erythrocytes are a biomarker of aging in the context of BBB integrity.

Novel YOF-Based Theranostic Agents with a Cascade Effect for NIR-II Fluorescence Imaging and Synergistic Starvation/Photodynamic Therapy of Orthotopic Gliomas

“…Then, the BBB model in vitro was constructed to assess the traverse competence of YMIGL using the monolayer b. End3 cerebrovascular endothelial cells (b End3 cells, Figure b). The trans-endothelial electrical resistance (TEER) values were above 190 Ω/cm 2 , proving the successful construction of the BBB model (Figure c) . Compared with the YMIG group, the green fluorescent emission can be observed in the YMIGL group, demonstrating that LF can assist YMIGL NPs to pass the BBB (Figure d).…”

“…The trans-endothelial electrical resistance (TEER) values were above 190 Ω/cm 2 , proving the successful construction of the BBB model (Figure 3c). 31 Compared with the YMIG group, the green fluorescent emission can be observed in the YMIGL group, demonstrating that LF can assist YMIGL NPs to pass the BBB (Figure 3d). The TEER value did not change after penetrating BBB, which proved that the BBB was not destroyed.…”

A nanotheranostic agent based on Nd3+-doped YVO4 with blood-brain-barrier permeability for NIR-II fluorescence imaging/magnetic resonance imaging and boosted sonodynamic therapy of orthotopic glioma

“…Successful establishment of the BBB was proved by the values of trans-endothelial electrical resistance (TEER), which exceeded 180 Ω cm -2 (Fig. 3d ) 37 . Then, FITC was loaded to the surface of YH@MnO 2 and YHM to evaluate their ability to penetrate the BBB.…”

In situ biosensing technologies for an organ-on-a-chip

“…Numerous other studies have employed the TEER method to test BBB models. For instance, Amiri et al produced a micro-electrical BBB (µE-BBB) chip employing TEER electrodes that were positioned on either side of the model comprising endothelial cells and astrocytes [57]. They analyzed the TEER to determine the difference between the BBB permeabilities of young and old erythrocytes.…”