title: Remodeling of axonal connections contributes to recovery in an animal model of multiple sclerosis.
abstract: 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.
authors.affiliation: Department of Neuromorphology, Brain Research Institute, University of Zurich, Switzerland. martink@mcb.harvard.edu
authors.forename: Martin
authors.initials: M
authors.lastname: Kerschensteiner
authors.forename: Florence M
authors.initials: FM
authors.lastname: Bareyre
authors.forename: Bigna S
authors.initials: BS
authors.lastname: Buddeberg
authors.forename: Doron
authors.initials: D
authors.lastname: Merkler
authors.forename: Christine
authors.initials: C
authors.lastname: Stadelmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
authors.forename: Thomas
authors.initials: T
authors.lastname: Misgeld
authors.forename: Martin E
authors.initials: ME
authors.lastname: Schwab
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D019922:GAP-43 Protein / Q000032:analysis; D009103:Multiple Sclerosis / Q000503:physiopathology*; D009416:Nerve Regeneration; D016501:Neurites / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology
chemical_list: D019922:GAP-43 Protein