1.A.146.  The Blood-Brain Barrier (BBB) Family 

The blood vessels that vascularize the central nervous system (CNS) confir the properties of the BBB (Waithe et al. 2024). The BBB allows these blood vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. The BBB is held together by tight junctions (see TC family 1.H.1) of the neighboring endothelial cells of the barrier, more specifically by tight junction proteins (TJPs or claudins), which can take the form of either integral transmembrane proteins or accessory cytoplasmic membrane proteins. BBB permeability can be affected by various factors, including but not limited to TJP expression, size, shape, charge, and type of extravascular molecules, as well as the nature of the vascular beds. The BBB is essential for proper maintenance of CNS function, and its structural integrity has been implicated in several disorders and conditions. For instance, it has been shown that in the cases of traumatic brain injury (TBI), TBI-associated edema, and increased intracranial pressure are primarily caused by cases of hyperpermeability seen because of BBB dysfunction. Intravital microscopy is a reliable method for measuring BBB hyperpermeability in rodent models of BBB dysfunction in vivo. Waithe et al. 2024 described the surgical and imaging methods for determining changes in BBB permeability at the level of the pial microvasculature in a mouse model of TBI using intravital microscopy.  See TC family 1.H.! for examples of claudins that may conprise BBBs.  The transporters associated with the BBB have been identified (Tremblay et al. 2024). The neuroprotective function of food-derived active peptides in CNS diseases, as well as the source of BBB penetrating peptides (BBB-shuttles) and the mechanisms of transmembrane transport have been reviewed (Li et al. 2023). Computational modeling of pharmaceuticals has been achieved with an emphasis on crossing the BBB (Alves et al. 2025).  The BBB is a crucial structure for maintaining homeostasis within the central nervous system, and its integrity plays a pivotal role in the onset and progression of epilepsy. Epileptic seizures can disrupt the molecular architecture of the BBB, including the loss of tight junction proteins (Huang et al. 2025).