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Improving repair and regeneration after spinal cord injury through combinatorial therapy (LB558)
Author(s) -
Torres Luisa,
Robinson John,
Tsirka Stella
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb558
Subject(s) - microglia , lesion , spinal cord injury , regeneration (biology) , medicine , spinal cord , neuroprotection , inflammation , neuroscience , glial scar , pathology , biology , microbiology and biotechnology , psychiatry
Spinal cord injury (SCI) results in the death of neurons, disruption of neuronal connections, demyelination, and inflammation. There are three phases of SCI: acute (from the time of impact to the first few days post‐injury), secondary (hours to weeks), and chronic (months to years). Most therapeutic interventions have focused on the secondary and chronic phases to promote healing and prevent further damage. However, little can be done to modify the acute phase. We show that the small molecule inhibitor Pifithrin‐µ (PFTμ), which prevents the association of p53 with Bcl/Bax without affecting p53’s transcriptional activity, significantly reduces lesion volume and modestly improves motor function in injured mice if applied immediately after injury. Similarly, application of microglia inhibitory factor (MIF/TKP) significantly reduces lesion volume and decreases microglial activation and secondary death. Combinatory use of PFTμ and MIF further improves motor function in mice. Given that PFTμ and MIF function via different mechanisms we anticipate that combining both approaches will result in improved histopathological outcomes in addition to improved motor coordination after SCI.