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  4. Selective Calpain Inhibition Improves Functional and Histopathological Outcomes in a Canine Spinal Cord Injury Model

Selective Calpain Inhibition Improves Functional and Histopathological Outcomes in a Canine Spinal Cord Injury Model

Int. J. Mol. Sci., 2022 · DOI: 10.3390/ijms231911772 · Published: October 4, 2022

NeurologyGeneticsVeterinary Medicine

Simple Explanation

This study investigates the use of a calpain inhibitor, PD150606, alone and in combination with methylprednisolone sodium succinate (MPSS) to treat spinal cord injury (SCI) in dogs. The results showed that the combination of MPSS and PD150606 was more effective in preventing neurodegeneration after SCI than either treatment alone. The study suggests that early treatment with MPSS and PD150606 after acute SCI may prevent further nerve damage through calpain inhibition.

Study Duration
8 Weeks
Participants
17 mongrel dogs
Evidence Level
Not specified

Key Findings

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    The combined administration of MPSS+PD150606 demonstrated considerably lower neuronal loss and microglial cell infiltration than the other groups, with a significant improvement in the locomotor score.
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    The increased levels of inflammatory markers (GFAP and CD11) and calcium-binding proteins (Iba1 and S100) were significantly reduced in the combination group.
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    The combined treatment effectively inhibited the calpain-induced cleavage of p35, limited cdk5 activation, and inhibited tau phosphorylation.

Research Summary

This study evaluated the therapeutic potential of a selective calpain inhibitor (PD150606) in combination with methylprednisolone sodium succinate (MPSS) in a dog SCI model. The findings revealed that the combined administration of MPSS+PD150606 demonstrated considerably lower neuronal loss and microglial cell infiltration than the other groups, with a significant improvement in the locomotor score. These results suggest that early MPSS+PD150606 therapy after acute SCI may prevent subsequent neurodegeneration via calpain inhibition.

Practical Implications

Clinical Treatment Strategies

The study suggests that combining MPSS with calpain inhibitors may improve outcomes in treating acute SCI.

Understanding Neurodegeneration

The research provides insight into the role of calpain activation in neurodegeneration following SCI.

Drug Development

The findings support further research into selective calpain inhibitors as therapeutic alternatives for SCI.

Study Limitations

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