title: Connexin43 mimetic peptide is neuroprotective and improves function following spinal cord injury.
abstract: 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.
authors: Department of Anatomy with Radiology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. s.ocarroll@auckland.ac.nz
authors: Simon J
authors: SJ
authors: O'Carroll
authors: Catherine A
authors: CA
authors: Gorrie
authors: Sailakshmi
authors: S
authors: Velamoor
authors: Colin R
authors: CR
authors: Green
authors: Louise F B
authors: LF
authors: Nicholson
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D018031:Connexin 43 / Q000008:administration & dosage / Q000494:pharmacology*; D007260:Infusion Pumps; D007278:Injections, Spinal; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D013904:Thoracic Vertebrae / Q000293:injuries
chemical_list: D018031:Connexin 43; C580592:Gja1 protein, rat; D018696:Neuroprotective Agents