The role of deimination as a response to trauma and hypoxic injury in the developing CNS

In higher vertebrates, including birds and mammals, damage after birth to the central nervous system (CNS), be it brain or spinal cord, results in permanent disability. In contrast, regeneration in developing embryos can occur until relatively late developmental stages. A key question in regenerative biology and medicine concerns the mechanisms underlying the transition from a regeneration-permissive to a non-permissive state, with the view that such understanding can help devise strategies for reducing damage and aiding repair following injury to the CNS. Another important question concerns whether the same pathways are activated in response to different types of neural insult and could be targeted for the development of much-needed novel therapeutic approaches. Peptidylarginine deiminases (PADs) are emerging as new early players in the response to neural damage and may also play important roles during development. Here we discuss findings concerning the putative role of PADs in response to neural damage and evidence that PAD inhibition can reduce the secondary injury response and tissue loss in different models of injury to the developing and perinatal/neonatal CNS.