Table 5.
Summary of factors in hyperglycemia that promote BBB disruption and risk of HT.
| Marker | Effect on BBB/consequences/contribution to risk of HT | References (for further reading) |
|---|---|---|
| Inflammation associated with diabetes | ||
| Increase in chronic inflammatory cytokines: TNF, IL-1β, IL-6, and PAI-1 | Impacting inflammation response (BBB permeability) PAI-1 interferes with tPa/alteplase degradation | (60) |
| NLRP3 Inflammasome | Associated with chronic inflammation in T2DM | (61) |
| Inflammation associated with hyperglycemia and ischemia | ||
| Activation of NF-κB. Inflammatory response: includes TNF, IL-1β, IL- 6, sICAM-1, ICAM-1, VCAM-1 and E-selectin activation. Source: astrocytes | Inflammatory cascade attracting leukocytes to the ischemic area. | (42) |
| Increase in MMP-9 (associated with ischemia) | Disruption of BBB | (54, 55) |
| Increased adhesion of neutrophils | NVU disruption | (62) |
| Increased superoxide production, NADPH | Disruption of BBB | (63) |
| Peroxynitrite | • HMGB1 leading to activating leukocytes and inflammatory cytokines. • Activation of NLRP3 leading to neutrophil recruitment and BBB disruption |
(9) (64) |
| Mechanical cellular changes due to chronic hyperglycemia | ||
| Capillary basement membrane thickening and enhanced microvascular permeability | Diabetes complications impacting the BBB structure | (60) |
| Decrease in pericytes | Diabetes complications impacting the BBB structure (NVU) | (65) |
| Decreased tight junction proteins (occludin and claudin-5) | Disruption of BBB | (66) |
BBB, blood-brain barrier; E-selectin, endothelial-leukocyte adhesion molecule 1; HMGB1, high mobility group box protein 1; ICAM-1, intercellular adhesion molecule-1; IL, interleukin; MMP, matrix metalloproteinase; NF-κB, nuclear factor-κB; NLRP3, NOD-, LRR- and pyrin domain-containing protein 3; NVU, neurovascular unit; PAI-1, plasminogen activator inhibitor-1; sICAM, soluble intercellular adhesion molecule; T2DM, type 2 diabetes; TNF, tumor necrosis factor; tPa, tissue plasminogen activator; VCAM-1, vascular cell adhesion molecule 1.