title: Critical role of connexin 43 in secondary expansion of traumatic spinal cord injury.
abstract: Spinal cord injury (SCI) is often complicated by secondary injury as a result of the innate inflammatory response to tissue trauma and swelling. Previous studies have shown that excessive ATP release from peritraumatic regions contributes to the inflammatory response to SCI by activation of low-affinity P2X7 receptors. Because connexin hemichannels constitute an important route for astrocytic ATP release, we here evaluated the impact on post-traumatic ATP release of deletion of connexins (Cx30/Cx43) in astrocytes. In vivo bioluminescence imaging showed a significant reduction in ATP release after weight-drop injury in mice with deletion of Cx43 compared with Cx43-expressing littermates, both on a Cx30 knockout background. Moreover, astrogliosis and microglia activation were reduced in peritraumatic areas of those mice lacking Cx43; motor recovery was also significantly improved, and the traumatic lesion was smaller. Combined, these observations are consistent with a contribution by astrocytic hemichannels to post-traumatic ATP release that aggravates secondary injury and restrains functional recovery after experimental spinal cord injury. Connexins may thereby constitute a new therapeutic target in spinal cord injury.
authors.affiliation: Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester, Rochester, New York 14642, USA.
authors.forename: Chunlan
authors.initials: C
authors.lastname: Huang
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Han
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.forename: Eric
authors.initials: E
authors.lastname: Lam
authors.forename: Weiguo
authors.initials: W
authors.lastname: Peng
authors.forename: Nanhong
authors.initials: N
authors.lastname: Lou
authors.forename: Arnulfo
authors.initials: A
authors.lastname: Torres
authors.forename: Meixiang
authors.initials: M
authors.lastname: Yang
authors.forename: Juan Mauricio
authors.initials: JM
authors.lastname: Garre
authors.forename: Guo-Feng
authors.initials: GF
authors.lastname: Tian
authors.forename: Michael V L
authors.initials: MV
authors.lastname: Bennett
authors.forename: Maiken
authors.initials: M
authors.lastname: Nedergaard
authors.forename: Takahiro
authors.initials: T
authors.lastname: Takano
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D018031:Connexin 43 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D018031:Connexin 43; C543076:GJA1 protein, mouse; D000255:Adenosine Triphosphate