A2B Adenosine Receptor as a New and Attractive Target to Treat Brain Ischemia or Demyelination

Ischemic stroke is one of the most prevalent vascular diseases worldwide that cause a decline in quality of life and a high mortality rate. Cerebral ischemia usually results in damage to white matter regions, especially the corpus callosum and the optic tract, with consequent demyelination. Animal models of stroke demonstrated that white matter injured after ischemia causes both axonal and myelin damage, thereby impacting behaviour and functional outcome after stroke. Oligodendrocyte precursor cells (OPCs) differentiate into mature oligodendrocyte, that is responsible for myelin production also in the adult brain. OPC migration, proliferation, and differentiation are altered after stroke, interfering, and limiting a functional recovery in this condition. Accumulated evidence indicates that after stroke, there is a strikingly release of adenosine, that may activate all its receptors, including the low-af!nity A2B subtype (A2BRs). After ischemia this receptor plays different and often contradictory roles, strictly depending on its cellular localisation (i.e. neuronal vs glial cells) indicating A2BRs as a novel and encouraging target to improve white matter integrity in stroke and demyelinating pathologies.