Effect of thymosin β4 on lipopolysaccharide‑stimulated brain microvascular endothelial cell remodeling: A possible role in blood‑brain barrier injury

• Published in: Experimental and therapeutic medicine 2023-08, Vol.26 (4), Article 468
• Main Authors: Stewart, William, Hejl, Christina, Guleria, Rakeshwar, Gupta, Sudhiranjan
• Format: Article
• Language: English
• Subjects: Apoptosis; Brain research; Cells; Cytokines; Gene expression; Homeostasis; Ischemia; Kinases; Mental disorders; Mental health; Permeability; Physiology; Proteins; R&D; Research & development; Traumatic brain injury
• ISSN: 1792-0981; 1792-1015
• DOI: 10.3892/etm.2023.12167

War veterans, in particular, are more prone to mental illness as they are more likely to have encountered multiple traumatic brain injuries (TBIs) whilst serving on active duty in war zone areas. A TBI is known to cause mortality or serious neurological disabilities among survivors and elicits a number of pathological processes, including neuroinflammation and blood brain barrier (BBB) disruption, leading to secondary brain damage and subsequent impairment of the neurovascular unit. Although several drugs exhibit promising effects for TBI, the repertoire of currently available therapeutic strategies remains limited. Thymosin 4 (Tβ4) is a 43-amino acid G-acting sequestering peptide that confers neuroprotective potential in TBI models. However, its role in BBB function remains unclear. Further research into the mechanism of BBB disruption induced by TBI and its specific role in neurovascular pathophysiology is necessary. In the present study, the protective effects of Tβ4 in lipopolysaccharide (LPS)-stimulated gene expression of several tight junction proteins, inflammatory genes, apoptotic genes, and adhesion genes in human brain microvascular endothelial cells (hBMVECs), one of the pivotal cell types in the BBB, were reported. The results suggested that pretreatment with Tβ4 reversed the LPS-induced damage of BBB components in hBMVECs. Furthermore, these results identified neuregulin 1 as a possible target for Tβ4. Therefore, it is proposed that Tβ4-mediated cellular signaling in hBMVEC may be vital for understanding the association between the BBB and TBI pathophysiology, which warrants further investigation.