Functional recovery after stroke using inosine

We have found that inosine, by activating neurons’ growth state, stimulates the rewiring of brain connections and improves functional outcome after spinal cord injury or stroke. Following a stroke restricted to one half of the cerebral cortex, inosine, delivered via osmotic minipump, caused nerve cells on the undamaged side of the brain to extend new axon branches that extended into brainstem areas which had lost their normal inputs following the damage.

We are currently investigating whether combining inosine treatment with agents to counteract inhibitory signals associated with myelin and/or the perineuronal net can enhance brain rewiring and functional improvement even further after injury. In studies led by Dr. Laila Zai, we are finding this to be the case. In behavioral tasks requiring skilled use of the paw contralateral to the stroke, we find that inosine alone, as well as an agent that partially counteracts growth-inhibitory signals, cause nerve fibers to extend new branches to the side of the spinal cord which had lost its normal input and lead to some improvement in behavior. However, when combined, inosine plus the other agent enabled animals to fully regain use of the denervated paw. This unprecedented outcome was accompanied by a strong enhancement in neural rewiring.