From the bench to bedside: Secondary spinal cord injury, ischemic penumbra after stroke, neural regulation of appetite, microglia in Rett syndrome, signaling pathways in peripheral nerve regeneration

Secondary injury in spinal cord injury has been postulated to be due to an inflammatory response propagated by excessive ATP release in surrounding traumatic areas. In this study, the authors explain that the mechanism behind the spread of ATP relies upon the presence of connexin43 (Cx43) channels. Connexins are hemichannels which, when connected with another hemichannel, form gap junctions between two neighboring cells. This allows for the transfer of small molecule nutrients and neurotransmitters that are necessary for cell–cell survival and communication. In order to study the effects of connexins on ATP release secondary to spinal cord injury, the authors utilized astrocytes lacking Cx43. ATP levels were detected and measured in both control and CX43 knockout (KO) mice after spinal cord injury. The researchers found that ATP levels, astrogliosis, and microglia activation were reduced in the KO mice lacking Cx43. Furthermore, the researchers assessed functional recovery of the mice by measuring compound action potentials (CAPs). They found that Cx43 KO mice exhibited improved preservation of spinal cord conduction than CX43 WT mice after spinal cord injury. This work suggests that Cx43 plays an important role in secondary inflammatory responses after spinal cord injury. With future research, Cx43 may be able to be targeted with an inhibitor and a neuroprotective treatment could be utilized in humans to minimize post-traumatic inflammation.