Figure 13.

Impaired FOCM and Elevated Hcy (HHcy) Results in an Activated Endothelium that Promotes Activated Fractalkine (CX3CL1). This collection of transmission electron micrographs from the female diabetic db/db models and diabetic BTBR ob/ob models in cortical grey matter (layer III) allow for illustrative and representative images that may also be present in Long COVID/post-acute sequelae of SARS-CoV-2 (LC/PASC). Impaired FOCM is associated with hyperhomocysteinemia (HHcy) and results in an activated endothelium with an attenuation and/or loss of endothelial glycocalyx (ecGCx) (yellows arrows pointing to lanthanum nitrate positively stained ecGCx) in the control model (panel (A)), which predisposes to the attenuation and/or loss of the ecGCx in diabetic BTBR ob/ob models and the development of microclots and microthrombi (panel (B)). Additionally, impaired FOCM with HHcy is associated with endothelial activation and dysfunction resulting in adhesion of red blood cell(s) (RBCs) (panel (C)) and adhesion of leukocytes such as lymphocytes (panel (D)) and monocytes (which may include the non-classical monocyte (CD14Lo, CD16+) (panel (E)). Magnifications vary and scale bars are included. This modified multi-panel figure is reproduced with permission by CC 4.0 [6,27,32,41].