The role of purinergic receptors in neural repair and regeneration after spinal cord injury

Abstract

Spinal cord injury is a serious injury of the central nervous system that results in neurological deficits. The pathophysiological mechanisms underlying spinal cord injury, as well as the mechanisms involved in neural repair and regeneration, are highly complex. Although there have been many studies on these mechanisms, there is no effective intervention for such injury. In spinal cord injury, neural repair and regeneration is an important part of improving neurological function after injury, although the low regenerative ability of nerve cells and the difficulty in axonal and myelin regeneration after spinal cord injury hamper functional recovery. Large amounts of ATP and its metabolites are released after spinal cord injury and participate in various aspects of functional regulation by acting on purinergic receptors which are widely expressed in the spinal cord. These processes mediate intracellular and extracellular signalling pathways to improve neural repair and regeneration after spinal cord injury. This article reviews research on the mechanistic roles of purinergic receptors in spinal cord injury, highlighting the potential role of purinergic receptors as interventional targets for neural repair and regeneration after spinal cord injury.

Keywords: glial cells; glial scar; inflammatory responses; neural regeneration; neural repair; neural stem cells; purinergic receptors; spinal cord injury.

Figure 1

P2X7, P2Y2, P2Y13, A1 and A2a receptors mediate oxidative stress response and inflammatory response after spinal cord injury. Intervention targeted to these receptors can regulate the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), as well as the release of inflammatory cytokines, such as tumor necrosis factor alpha-α (TNF-α), interleukin (IL)-6 and IL-1β, so as to reduce neuronal apoptosis and histological lesions after spinal cord injury.

Figure 2

Purinergic receptors expressed in a variety of glial cells play an important role in nerve repair and regeneration after spinal cord injury. P2X4, P2X7, P2Y12 and A1 receptors expressed in the microglia; P2Y1 and P2Y12 receptors expressed in oligodendrocytes and P2Y13 receptors expressed in astrocytes play an important role in nerve repair and regeneration after spinal cord injury (SCI). Inhibition of the P2X4, P2X7 and P2Y1 receptors attenuate neurodegeneration based on excitotoxicity. A1, P2Y12 and P2Y13 receptors play a neuroprotective role and inhibit gliosis, thereby reducing histological damage and dysfunction after SCI.