TY - JOUR
T1 - Critical role of connexin 43 in secondary expansion of traumatic spinal cord injury
AU - Huang, Chunlan
AU - Han, Xiaoning
AU - Li, Xi
AU - Lam, Eric
AU - Peng, Weiguo
AU - Lou, Nanhong
AU - Torres, Arnulfo
AU - Yang, Meixiang
AU - Garre, Juan Mauricio
AU - Tian, Guo Feng
AU - Bennett, Michael V.L.
AU - Nedergaard, Maiken
AU - Takano, Takahiro
PY - 2012/3/7
Y1 - 2012/3/7
N2 - 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.
AB - 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.
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U2 - 10.1523/JNEUROSCI.1216-11.2012
DO - 10.1523/JNEUROSCI.1216-11.2012
M3 - Article
C2 - 22399755
AN - SCOPUS:84863248130
SN - 0270-6474
VL - 32
SP - 3333
EP - 3338
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 10
ER -