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Background: <p>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.</p> Methods: <p>We developed a model of mice with repetitive and mild TBI following a weight-drop once a day for 5&#xa0;days. PLX3397 (50&#xa0;mg/kg, p. o.) was administered for 21&#xa0;days. Intranasal administration of hNTSCs (1 × 10<sup>6</sup>) was performed once.</p> Results: <p>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.</p> Conclusion: <p>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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年3月5日

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  • Jung Eun Lee,
  • Jung Yeon Lim,
  • Seung Yoon Song,
  • Sun Hwa Park,
  • Jai Ho Choi,
  • Hyun Kook Lim,
  • Sung Won Kim,
  • Seung Ho Yang

摘要

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.