Grant: Operating Grant

In contrast to the peripheral nervous system, nerve cells in the central nervous system (CNS: i.e. brain or spinal cord) cannot spontaneously regenerate their connections. Consequently, after a spinal cord injury (SCI) individuals permanently suffer from the loss of sensory, motor, and autonomic function below the level of the injury. Unfortunately there is still no effective treatment to repair the injured spinal cord. A reason for the lack of an efficient treatment despite years of intensive research is that regeneration of nerve cell branches in the CNS is inhibited by multiple factors. Therefore, it is now widely agreed upon that an effective treatment for SCI will have to address various obstacles for nerve cell regeneration at the same time. A possibility to circumvent the necessity for regeneration of nerve cells originating in the brain following SCI, but still promoting their reconnection to targets that lost their input from the brain below the lesion, is based on findings following incomplete SCI. Our research has shown that injured nerve cells spontaneously sprout new branches above the lesion site and connect to descending nerve cells spared by the lesion. Thereby, these injured cells are reconnecting to their original targets via a relay. A possible relay following complete SCI are nerve cells located in the spinal cord, so called interneurons, that have demonstrated a superior ability to regenerate. Therefore, the goal of this proposal is to extend our previous combined treatment in rats with complete SCI, with the focus to enhance regeneration of interneurons. Then, we will encourage rerouting of injured nerve cells originating in the brain via these interneurons, in order to indirectly reconnect them to spinal networks below the injury.