Remote cell death in the cerebellar system

Functional impairment after focal CNS lesion is highly dependent on damage that occurs in regions that are remote but functionally connected to the primary lesion site. This pattern is particularly evident in the cerebellar system, in which functional interactions between the cerebellar cortex, deep cerebellar nuclei, and precerebellar stations are of paramount importance. Diffuse degeneration after development of a focal CNS lesion has been associated with poor outcomes in several pathologies, such as stroke, multiple sclerosis, and brain trauma. A greater understanding of the mechanisms that underlie the spread of death signals from focal lesions, however, can aid in identifying a neuroprotective approach for CNS pathologies. To this end, studies on degenerative mechanisms in the inferior olive and pontine nuclei after focal cerebellar damage have been a valuable asset in which pharmacological approaches have been tested. In this review, we focus on mechanisms of remote cell death in cerebellar circuits, analyzing the neuroprotective effects of inflammation-modulating drugs in particular.