Angiotensin II Receptor Signaling in the Hypothalamic-Pituitary-Adrenal Axis and Spleen After Spinal Cord Injury Depends on the Sympathetic Innervation Integrity.

Traumatic brain injury (TBI) is a leading cause of long‐term neurological disability and remains a serious public health concern worldwide [, ]. Beyond the immediate mechanical injury, TBI also triggers a cascade of secondary processes including neurovascular disruption, neuroinflammation, and maladaptive remodeling which can persist for weeks or even years [, ]. A central consequence of this process is the breakdown of the blood–brain barrier (BBB) and long‐term endothelial dysfunction, leading to white matter and neuronal loss [, ]. Yet, despite decades of research, effective pharmacological therapies capable of restoring BBB integrity and promoting long‐term functional recovery remain elusive. Increasing evidence suggests the brain endothelium is not just a passive barrier but an active orchestrator of neural repair after TBI [, , ]. Endothelial cells within the neurovascular unit are known to integrate mechanical and chemical cues to regulate angiogenesis, inflammation, and metabolic support [, , ], while also functioning as signaling hubs to coordinate neurovascular responses to brain injury []. Thus, identifying the molecular switches that govern endothelial dysfunction during the chronic phase of TBI is critical for developing restorative therapies. MicroRNAs (miRNAs) are potent post‐transcriptional regulators of endothelial function and vascular homeostasis [, , ]. Among them, the cluster has emerged as a key regulator of cerebrovascular integrity []. Our previous work demonstrated that global genetic deletion or pharmacological inhibition of protects the brain across multiple disease settings, including ischemic stroke, vascular dementia, and TBI, by attenuating neuroinflammation, BBB disruption, neuronal loss, white matter degeneration, and promoting cerebral angiogenesis [, , , , , , , ]. While these findings have established as a crucial regulator of the brain response to ischemic or traumatic insults, whether its therapeutic efficacy stems from an endothelial‐intrinsic mechanism and its downstream molecular effectors remain unknown.