Intranasal Administration of Human Neural Crest-Derived Nasal Turbinate Stem Cells Attenuates Microglia Activity in Mild Head Trauma Models

Background: Mild head trauma often leads to long-term cognitive and neurological deficits. PLX3397, an inhibitor of colony-stimulating factor 1 receptor (CSF1R), offers promise as a therapeutic agent for traumatic brain injury (TBI) by targeting neuro-inflammation. Stem cell-based approaches are widely studied for neurological disorders. The objective of this study was to investigate therapeutic effect of intranasal administration of human neural crest-derived nasal turbinate stem cells (hNTSCs) on mild TBI in comparison with that of PLX3397. Methods: We developed a model of mice with repetitive and mild TBI following a weight-drop once a day for 5 days. PLX3397 (50 mg/kg, p. o.) was administered for 21 days. Intranasal administration of hNTSCs (1 × 10⁶) was performed once. Results: Iba1 + and GFAP + cells were increased in the cortex and hippocampus of TBI models. Iba1 + cells and GFAP + cells were remarkably decreased in PLX3397 or hNTSC-treated TBI models. Administration of PLX3397 attenuated the decrease in neurobehavioral activity. Similar effects were observed in a TBI model with a single dose of hNTSC. Conclusion: Intranasal administration of hNTSCs had a microglia-depleting effect. Administered hNTSCs were found around the cortex and hippocampus of TBI brains. This investigation may provide a promising path for therapeutic initiatives for repetitive and mild TBI.