Blood-derived factors to brain communication in brain diseases

Brain diseases, mainly including acute brain injuries, neurodegenerative diseases, and mental disorders, have posed a significant threat to human health worldwide. Due to the limited regenerative capability and the existence of the blood-brain barrier, the brain was previously thought to be separated from the rest of the body. Currently, various cross-talks between the central nervous system and peripheral organs have been widely described, including the brain-gut axis, the brain-liver axis, the brain-skeletal muscle axis, and the brain-bone axis. Moreover, several lines of evidence indicate that leveraging systemic biology intervention approaches, including but not limited to lifestyle interventions, exercise, diet, blood administration, and peripheral immune responses, have demonstrated a significant influence on the progress and prognosis of brain diseases. The advancement of innovative proteomic and transcriptomic technologies has enriched our understanding of the nuanced interplay between peripheral organs and brain diseases. An array of novel or previously underappreciated blood-derived factors have been identified to play pivotal roles in mediating these communications. In this review, we provide a comprehensive summary of blood-to-brain communication following brain diseases. Special attention is given to the instrumental role of blood-derived signals, positing them as significant contributors to the complex process of brain diseases. The insights presented here aim to bridge the current knowledge gaps and inspire novel therapeutic strategies for brain diseases.