Thymosin 4 was found to reverse the damage caused by lipopolysaccharide stimulation on blood-brain barrier components. It preserved the expression of tight junction proteins, prevented inflammation and apoptosis, and reduced endothelial cell permeability.
Article published in journal Experimental and Therapeutic Medicine discusses the regulation of the blood-brain barrier (BBB) and its dysfunction in the context of traumatic brain injury (TBI). The BBB is a protective barrier that separates the brain from the bloodstream and regulates the exchange of molecules between the two compartments. Dysfunction of the BBB can occur following TBI, leading to increased permeability and disruption of normal brain function.
The article highlights the importance of understanding the cellular and molecular mechanisms underlying BBB dysfunction in TBI. cellular infiltration plays a role in TBI-induced BBB dysfunction, and that microvascular disruption contributes to brain damage. The breakdown of the BBB is associated with neuroinflammation and the development of cerebral edema, which can further exacerbate brain injury.
The authors also discuss the role of specific proteins involved in maintaining BBB integrity, such as claudin-5 and ZO proteins. They mention that targeted suppression of claudin-5 can decrease cerebral edema and improve cognitive outcomes in TBI. Additionally, the involvement of various factors, including microRNAs and inflammatory mediators, in BBB dysfunction also plays role.
Understanding the mechanisms underlying BBB dysfunction in TBI is crucial for the development of potential therapeutic strategies to mitigate brain damage and improve patient outcomes.
BBB disruption can result in brain edema, structural protein breakdown, and cell death. It can also contribute to secondary brain damage and impairment of the neurovascular unit. The BBB plays a crucial role in maintaining brain homeostasis by regulating the exchange of nutrients and preventing the entry of toxic molecules and immune cells. TBI-induced BBB disruption can lead to increased permeability and leakage, causing cytotoxicity and neuronal damage. Additionally, TBI can activate glial cells, which further contribute to BBB disruption through the release of inflammatory molecules.
Thymosin 4 (Tβ4) has shown potential therapeutic effects in protecting the blood-brain barrier by preserving the expression of tight junction proteins, reducing inflammation, preventing apoptosis, and regulating vascular gene expression.
In studies using human brain microvascular endothelial cells (hBMVECs), Tβ4 pre-treatment was found to reverse the damage caused by lipopolysaccharide (LPS) stimulation, which is known to induce BBB disruption. Tβ4 preserved the expression of tight junction proteins, which are crucial for maintaining the integrity of the BBB. It also reduced the expression of inflammatory mediators, such as IL-6, IL-1β, and TNFα, suggesting an anti-inflammatory role. Additionally, Tβ4 prevented the upregulation of adhesion molecules, such as ICAM1 and VCAM1, which are involved in the adhesion and migration of inflammatory cells.
Furthermore, Tβ4 was shown to protect against LPS-induced dysfunction in endothelial cell permeability. LPS treatment increased the permeability of hBMVECs, but this increase was significantly prevented by Tβ4 pre-treatment. This suggests that Tβ4 may offer protection against LPS-induced disruption of endothelial cell permeability, thereby preserving the barrier function of the BBB.
TBI has a detrimental impact on the integrity and function of the neurovascular unit.
Tβ4 has demonstrated potential therapeutic effects in protecting the BBB by preserving tight junction proteins, reducing inflammation, preventing apoptosis, and regulating vascular gene expression. Further research is needed to both understand the complex interactions and signaling pathways involved in BBB regulation and dysfunction in the context of TBI as well as the mechanism of action and the specific role of Tβ4 in neurovascular pathophysiology.
Whole article can be found here: