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

• Published in: Neuroscience research 2013-03, Vol.75 (3), p.256-267
• Main Authors: O’Carroll, Simon J., Gorrie, Catherine A., Velamoor, Sailakshmi, Green, Colin R., Nicholson, Louise F.B.
• Format: Article
• Language: English
• Subjects: Animals; Behavior, Animal - drug effects; Behavior, Animal - physiology; Connexin; Connexin 43 - administration & dosage; Connexin 43 - pharmacology; Cytokines; Infusion Pumps; Injections, Spinal; Male; Mimetic peptide; Neuroinflammation; Neuroprotection; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - pharmacology; Rats; Rats, Sprague-Dawley; Recovery of Function - drug effects; Spinal Cord Injuries - drug therapy; Spinal Cord Injuries - etiology; Spinal Cord Injuries - physiopathology; Spinal cord injury; Thoracic Vertebrae - injuries
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2013.01.004

► We tested if connexin43 modulation was protective in spinal cord injury. ► We examined changes in behaviour, neuroinflammation and neuronal survival. ► Treatment with mimetic peptide led to an improvement in locomotion. ► Treatment led to a reduction in the degree of neuroinflammation ► Treatment led to improved neuronal survival. 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 10g, 12.5mm 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 24h after injury. Treatment with Peptide5 led to significant improvements in hindlimb function as assessed using the Basso–Beattie–Bresnahan scale. Peptide5 caused a reduction in Cx43 protein, increased Cx43 phosphorylation and decreased levels of TNF-α and IL-1β 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.