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Aims <p>This study evaluated the therapeutic effects, both beneficial and adverse, of Cerebrolysin (CBL) as an adjuvant to bone marrow-derived mesenchymal stem cells (BM-MSCs) in enhancing functional recovery after spinal cord injury (SCI) in female Wistar rats.</p> Methods <p>Female Wistar rats were randomly assigned to five groups: sham, SCI, SCI/BM-MSCs, SCI/CBL, and SCI/BM-MSCs/CBL. Locomotor and sensory functions were assessed using the BBB scale, inclined plane, and hot plate tests. Inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-4, IL-10), caspase activity, malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, and tissue cavity size were measured to evaluate biochemical and histological changes.</p> Results <p>The combination therapy (SCI/MSC/CBL) demonstrated superior locomotor recovery (BBB scores: <i>P</i> &lt; 0.001 vs. monotherapies from day 7) and sensory function improvement (inclined plane/hot plate: <i>P</i> &lt; 0.01). Mechanistically, SCI/MSC/CBL exhibited the lowest pro-inflammatory cytokines (IL-1β, TNF-α: <i>P</i> &lt; 0.01) and highest anti-inflammatory cytokines (IL-4, IL-10), alongside reduced caspase-3 activity (<i>P</i> &lt; 0.001 vs. SCI), indicating concurrent immunomodulation and anti-apoptotic effects. Oxidative stress mitigation was evident through the lowest MDA levels (<i>P</i> &lt; 0.05) and highest SOD activity, while histological analysis revealed minimal cavity size (10.5 ± 2.1 vs. SCI’s 28.25 ± 2.9; <i>P</i> &lt; 0.001).</p> Conclusion <p>Co-administration of BM-MSCs and CBL synergistically modulates neuroprotective pathways, suppressing inflammation, inhibiting apoptosis, and attenuating oxidative stress. These multi-mechanistic synergies underpin enhanced functional and histological recovery, supporting this combinatorial strategy for SCI therapy.</p> Lay summary <p>This study tested whether combining bone marrow stem cells (BM-MSCs) and the drug Cerebrolysin (CBL) improves recovery after spinal cord injury in rats better than either treatment alone. Compared to single treatments, the combination therapy significantly enhanced movement, reduced inflammation and cell death, and minimized spinal cord damage. The results suggest that using both BM-MSCs and CBL together could be a promising treatment for spinal cord injuries.&#xa0;</p>

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Synergistic Neuroregenerative Effects of Cerebrolysin and Bone Marrow-Derived Mesenchymal Stem Cells in a Rat Model of Spinal Cord Injury

  • 期刊论文

  • 发表日期：

    2025年9月23日

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  • Narges Ghayour,
  • Ramin Haji-khani,
  • Gholamreza Bahadorkhan,
  • Maryam Khosravi,
  • Saeid Zibaei

摘要

Aims

This study evaluated the therapeutic effects, both beneficial and adverse, of Cerebrolysin (CBL) as an adjuvant to bone marrow-derived mesenchymal stem cells (BM-MSCs) in enhancing functional recovery after spinal cord injury (SCI) in female Wistar rats.

Methods

Female Wistar rats were randomly assigned to five groups: sham, SCI, SCI/BM-MSCs, SCI/CBL, and SCI/BM-MSCs/CBL. Locomotor and sensory functions were assessed using the BBB scale, inclined plane, and hot plate tests. Inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-4, IL-10), caspase activity, malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, and tissue cavity size were measured to evaluate biochemical and histological changes.

Results

The combination therapy (SCI/MSC/CBL) demonstrated superior locomotor recovery (BBB scores: P < 0.001 vs. monotherapies from day 7) and sensory function improvement (inclined plane/hot plate: P < 0.01). Mechanistically, SCI/MSC/CBL exhibited the lowest pro-inflammatory cytokines (IL-1β, TNF-α: P < 0.01) and highest anti-inflammatory cytokines (IL-4, IL-10), alongside reduced caspase-3 activity (P < 0.001 vs. SCI), indicating concurrent immunomodulation and anti-apoptotic effects. Oxidative stress mitigation was evident through the lowest MDA levels (P < 0.05) and highest SOD activity, while histological analysis revealed minimal cavity size (10.5 ± 2.1 vs. SCI’s 28.25 ± 2.9; P < 0.001).

Conclusion

Co-administration of BM-MSCs and CBL synergistically modulates neuroprotective pathways, suppressing inflammation, inhibiting apoptosis, and attenuating oxidative stress. These multi-mechanistic synergies underpin enhanced functional and histological recovery, supporting this combinatorial strategy for SCI therapy.

Lay summary

This study tested whether combining bone marrow stem cells (BM-MSCs) and the drug Cerebrolysin (CBL) improves recovery after spinal cord injury in rats better than either treatment alone. Compared to single treatments, the combination therapy significantly enhanced movement, reduced inflammation and cell death, and minimized spinal cord damage. The results suggest that using both BM-MSCs and CBL together could be a promising treatment for spinal cord injuries.