Semaglutide Promotes Angiogenesis and Blood-Brain Barrier Repair After Traumatic Brain Injury via PDGF-BB/PDGFRβ Signaling

Repair of the blood-brain barrier (BBB) and promotion of angiogenesis are critical for recovery after traumatic brain injury (TBI). However, the uncoordinated timing of angiogenesis and BBB integrity can worsen brain edema and neuronal loss, limiting current therapeutic strategies. While Semaglutide has demonstrated neuroprotective effects in various neurological disorders, its specific mechanisms for BBB repair and angiogenesis in TBI contexts have remained largely undefined, representing a key gap in understanding its full therapeutic potential.

Researchers utilized a mouse controlled cortical impact (CCI) model to investigate the effects of Semaglutide on BBB repair, angiogenesis, and the endothelial cell (EC)-pericyte (PC) axis. The study aimed to clarify the underlying mechanisms of Semaglutide's protective effects by detecting and analyzing key molecular markers and signaling pathways involved in these processes. The abstract does not specify the dose, route, frequency, or duration of Semaglutide administration, nor the exact number of animals (n) used in the study.

Semaglutide significantly upregulated platelet-derived growth factor-BB (PDGF-BB) expression within the peri-lesional brain tissue. This increased PDGF-BB subsequently activated pericytes via platelet-derived growth factor receptor β (PDGFRβ), leading to enhanced secretion of angiopoietin-1 (Ang-1) and vascular endothelial growth factor (VEGF). This cascade not only promoted angiogenesis but also critically enhanced BBB integrity by fostering the survival of both pericytes (PC) and endothelial cells (EC), alongside upregulating tight junction proteins. These combined effects ultimately contributed to reduced brain edema and improved neurological function recovery after TBI. Mechanistically, the PDGF-BB/PDGFRβ, Ang-1/Tie2, and PI3K/AKT pathways were identified as key mediators in Semaglutide's interactions between EC and PC.

Semaglutide's action on the PDGF-BB/PDGFRβ pathway in pericytes was central to promoting both angiogenesis and BBB integrity, leading to reduced edema and improved neurological recovery post-TBI.