Thyroid Hormone T4 Alleviates Traumatic Brain Injury by Enhancing Blood–Brain Barrier Integrity

Traumatic brain injury (TBI) disrupts the blood-brain barrier (BBB), resulting in increased permeability, neuronal loss, and cognitive dysfunction. This study investigates the therapeutic potential of thyroid hormone (T4) to reduce BBB dysfunction following moderate fluid percussion injury. T4 injection (intraperitoneal) after TBI restores the levels of pericytes and endothelial cells vital for BBB integrity, reduces edema by downregulating AQP-4 gene expression, and enhances levels of the tight junction protein ZO-1. T4 counteracts the TBI-related increase in MMP-9 and TLR-4, significantly reducing BBB permeability. Furthermore, T4 enhances the neuroprotective functions of astrocytes by promoting the activity of A2 astrocytes. Additionally, T4 treatment increases DHA levels (important for membrane integrity and function), stimulates mitochondrial biogenesis, and leads to a notable improvement in spatial learning and memory retention. These findings suggest that T4 has significant potential to reduce vascular leakage and inflammation after TBI, thereby improving cognitive function and maintaining BBB integrity.