Sex-Specific Effects of Dexmedetomidine on Brain Microvascular Endothelial Cell Function After Traumatic Brain Injury in Juvenile Mice.

AIMS: This study aimed to evaluate the effects of dexmedetomidine (DEX), a selective α2-adrenergic receptor agonist, on brain microvascular endothelial cell (BMEC) function and blood-brain barrier (BBB) integrity in juvenile mice following traumatic brain injury (TBI). We specifically assessed the effects of DEX on ER stress, neuroinflammation, and ferroptosis and explored potential sex-specific responses.

METHODS

Male and female juvenile mice were subjected to an impact-acceleration TBI model. DEX was administered during the acute phase post-injury. Muscle strength and sensorimotor coordination were measured, and BBB permeability was assessed. BMECs and cerebral microvessels were isolated from the injured and control regions for molecular analysis of inflammatory markers, ER stress activation, ferroptosis, and expression of tight junction markers.

RESULTS

DEX treatment improved motor and coordination outcomes and reduced BBB leakage in both sexes after TBI. Molecular analyses revealed decreased inflammatory signaling, ER stress, and ferroptosis-related oxidative stress pathways in BMECs with DEX treatment. Importantly, DEX led to greater upregulation of selected tight junction markers in female mice than in male mice, suggesting possible sex-specific differences in α2-adrenergic receptor expression.

CONCLUSION

DEX provides both behavioral and cellular protection following juvenile TBI, with potential sex-dependent effects on BMECs and BBB function.