A research team at Keio University has identified that miR-9-3p contained in cerebrospinal fluid (CSF) extracellular vesicles (EVs) can serve as a novel biomarker capable of predicting spontaneous functional recovery and exhibits neuroprotective responses after spinal cord injury (SCI). The team was led by Dr. Narihito Nagoshi, Assistant Professor at the Department of Orthopaedic Surgery, Keio University School of Medicine; Hideyuki Okano, Director of the Keio University Regenerative Medicine Research Center; Dr. Tomoharu Tanaka, Assistant Professor; and Satoru Morimoto, Associate Professor/Vice Director.
Although biomarker development for SCI has been actively pursued worldwide, no biomarker has yet been established that can predict the potential for spontaneous recovery during the early phase after injury. To address this gap, the research team performed a comprehensive analysis of CSF-derived EVs. In rat SCI models, they identified a marked increase in miR-9-3p levels in CSF-derived EVs following injury. Furthermore, in human CSF samples, miR-9-3p levels were significantly higher in the non-recovery group than in the spontaneous recovery group, demonstrating its usefulness as a prognostic biomarker.
In addition, in an acute SCI rat model, miR-9-3p expression decreased at the spinal lesion site but increased in the brain, where it was found to be highly expressed in astrocytes. These findings suggest that miR-9-3p may be actively secreted from astrocytes in the brain as a compensatory response to spinal cord injury. Analysis using human-derived motor neurons further revealed that miR-9-3p regulates genes associated with suppression of energy metabolism, synaptic plasticity, and stress responses, suggesting its involvement in adaptive neuroprotective responses.
These findings provide new insights into intercellular communication within the central nervous system during the acute phase of SCI and suggest that CSF EV-derived miR-9-3p may serve as both a novel biomarker for predicting spontaneous recovery and a therapeutic target.
The findings were published online in Communications Biology on October 27, 2025, at 18:00 JST.
