In multiple sclerosis (MS), inflammation in the central nervous system (CNS) 
leads to damage of axons and myelin. Early during the clinical course, patients 
can compensate this damage, but little is known about the changes that underlie 
this improvement of neurological function. To study axonal changes that may 
contribute to recovery, we made use of an animal model of MS, which allows us to 
target inflammatory lesions to the corticospinal tract (CST), a major descending 
motor pathway. We demonstrate that axons remodel at multiple levels in response 
to a single neuroinflammatory lesion as follows: (a) surrounding the lesion, 
local interneurons show regenerative sprouting; (b) above the lesion, descending 
CST axons extend new collaterals that establish a "detour" circuit to the lumbar 
target area, whereas below the lesion, spared CST axons increase their terminal 
branching; and (c) in the motor cortex, the distribution of projection neurons 
is remodeled, and new neurons are recruited to the cortical motor pool. 
Behavioral tests directly show the importance of these changes for recovery. 
This paper provides evidence for a highly plastic response of the motor system 
to a single neuroinflammatory lesion. This framework will help to understand the 
endogenous repair capacity of the CNS and to develop therapeutic strategies to 
support it.