Initial behavioral deficits resulting from brain injury are frequently followed by spontaneous recovery of function. The basis of this behavioral plasticity is not fully understood, although neural network reorganization is expected to contribute to this resilience. It has been noted that synaptic plasticity within pre-existing pathways and formation of new circuits through collateral sprouting of both lesioned and unlesioned fibers are important components of the spontaneous recovery process, although the molecular mechanisms of these phenomena are poorly understood. We aim to elucidate the mechanisms underlying this plasticity, knowledge of which will contribute to enhancement of functional recovery after injury to the central nervous system. We have explored the mechanism of this behavioral plasticity (Brain, 2013), and more importantly, we have obtained evidence to show that immune modulation, inflammation-induced neovessels, and some types of microglia enhance plasticity and survival of neurons by secreting trophic factors (Nat. Med., 2012; Nat. Neurosci., 2013). These immune cells, neovessels, and microglia may prove to be drug targets for the treatment of CNS injuries, CNS inflammation, and neurodegenerative diseases. Focusing on the corticospinal tract, which is one of the main neuronal tracts that regulate motor function, I will talk about our recent findings that uncover the molecular mechanism of formation and restoration of corticospinal tract.