Connexin43 mimetic peptide is neuroprotective and improves function following spinal cord injury

Publisher:
Wiley-Liss
Publication Type:
Journal Article
Citation:
Journal Of Neuroscience Research, 2013, 75 (3), pp. 256 - 267
Issue Date:
2013-01
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Connexin43 (Cx43) is a gap junction protein up-regulated after spinal cord injury and is involved in the on-going spread of secondary tissue damage. To test whether a connexin43 mimetic peptide (Peptide5) reduces inflammation and tissue damage and improves function in an in vivo model of spinal cord injury, rats were subjected to a 10 g, 12.5 mm weight drop injury at the vertebral level T10 using a MASCIS impactor. Vehicle or connexin43 mimetic peptide was delivered directly to the lesion via intrathecal catheter and osmotic mini-pump for up to 24 h after injury. Treatment with Peptide5 led to significant improvements in hindlimb function as assessed using the BassoBeattieBresnahan scale. Peptide5 caused a reduction in Cx43 protein, increased Cx43 phosphorylation and decreased levels of TNF-a and IL-1ß as assessed by Western blotting. Immunohistochemistry of tissue sections 5 weeks after injury showed reductions in astrocytosis and activated microglia as well as an increase in motor neuron survival. These results show that administration of a connexin mimetic peptide reduces secondary tissue damage after spinal cord injury by reducing gliosis and cytokine release and indicate the clinical potential for mimetic peptides in the treatment of spinal cord patients.
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