ABSTRACT
There are multiple studies reporting changes to connexin expression associated with central nervous system (CNS) injury mechanisms and inŽammatory processes (for review, see Kielian 2008; Chew et al. 2010). Areas of maximal tissue damage may show lower connexin levels (generally reŽecting cell death), but the most commonly reported response is connexin43 (Cx43) upregulation, either in the wounded area or in tissue immediately surrounding the damaged sector. This upregulation correlates closely with a number of inŽammatory events, in particular secondary damage or lesion spread, white blood cell inŸltration or glial cell activation, and endothelial cell activation leading to a breakdown in the bloodbrain barrier. Gap junction modulation has been identiŸed as a potential neuroprotective target in events such as traumatic brain injury, optic nerve and retinal ischemia, spinal cord injury or repair, and for chronic neurodegenerative diseases. Section 14.2 brieŽy introduces the key inŽammatory events involving gap junction communication and hemichannel roles relevant to this chapter (for more speciŸc details refer to the Prequel and Chapters 1 and 3 of this book). Examples of both ex vivo and in vivo models are then presented in which communication levels have been modulated following CNS injury, at the level of a gene knockout or through transient modulation, primarily with connexin-speciŸc antisense oligonucleotides or functional connexin peptidomimetics.
