Systemic administration of Connexin43 mimetic peptide improves functional recovery following traumatic spinal cord injury in adult rats.

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Journal Article
Journal of neurotrauma, 2017, 34 (3), pp. 707 - 719
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Blocking of Connexin43 hemichannels, the main gap junction protein located on astrocytes in the central nervous system, has been shown to reduce neural injury in a number of models. We previously demonstrated that local administration of a Connexin43 mimetic peptide, Peptide5, reduces secondary tissue damage after spinal cord injury (SCI). Here, we investigated whether acute systemic delivery of Peptide5 is also protective in a model of SCI. Rats were subjected to a mild spinal cord contusion using the MASCIS impactor and were injected intraperitoneally with Peptide5 or a scrambled peptide immediately and at 2 and 4 hours post-injury. Rats were tested for locomotor recovery and pain hypersensitivity and euthanised at 8 hours, 24 hours, 2 weeks or 6 weeks post-injury. Compared to control rats, Peptide5 treated rats showed significant improvement in hindlimb locomotor function between 3 and 6 weeks post-injury and reductions in at-level mechanical allodynia from week 1 post-injury. Immunohistochemistry showed that Peptide5 treatment led to a reduction in total Connexin43 and increased phosphorylated Connexin43 at 8 hours compared to scrambled peptide. At 2 and 6 weeks, lesion size, the astrocytic and the activated macrophage and/or microglial response were all decreased in the Peptide5 animals. Additionally, neuronal cell numbers were higher in the Peptide5 animals compared to the scrambled peptide treated rats at 2 and 6 weeks. These results show for the first time that systemic administration of Peptide5 to block the pathological opening of Connexin43 hemichannels is a feasible treatment strategy in this setting, ameliorating the secondary SCI.
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