title: Neuroaxonal regeneration is more pronounced in early multiple sclerosis than in traumatic brain injury lesions.
abstract: The extent of irreversible neuroaxonal damage is the key determinant of permanent disability in traumatic and inflammatory conditions of the central nervous system (CNS). Structural damage is nevertheless in part compensated by neuroplastic events. However, it is unknown whether the same kinetics and mechanisms of neuroaxonal de- and regeneration take place in inflammatory and traumatic conditions. We analyzed neuroaxonal degeneration and plasticity in early multiple sclerosis (MS) lesions and traumatic brain injury (TBI). Neuroaxonal degeneration identified by the presence of SMI31+ chromatolytic neurons and SMI32+ axonal profiles were characteristic features of leukocortical TBI lesions. Axonal transport disturbances as determined by amyloid precursor protein (APP)+ spheroids were present in both TBI and MS lesions to a similar degree. Neurons expressing growth-associated protein 43 (GAP43) and synaptophysin (Syn) were found under both pathological conditions. However, axonal swellings immunopositive for GAP43 and Syn clearly prevailed in subcortical MS lesions, suggesting a higher regenerative potential in MS. In this context, GAP43+/APP+ axonal spheroid ratios correlated with macrophage infiltration in TBI and MS lesions, supporting the idea that phagocyte activation might promote neuroplastic events. Furthermore, axonal GAP43+ and Syn+ swellings correlated with prolonged survival after TBI, indicating a sustained regenerative response.
authors.affiliation: Department of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Lucas
authors.initials: L
authors.lastname: Schirmer
authors.forename: Doron
authors.initials: D
authors.lastname: Merkler
authors.forename: Fatima B
authors.initials: FB
authors.lastname: König
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
authors.forename: Christine
authors.initials: C
authors.lastname: Stadelmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D001369:Axons / Q000473:pathology / Q000502:physiology*; D001706:Biopsy; D001930:Brain Injuries / Q000473:pathology* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology*; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology* / Q000503:physiopathology; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D012038:Regeneration / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism; D055815:Young Adult
chemical_list: D016564:Amyloid beta-Protein Precursor; D019922:GAP-43 Protein; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; C569014:SYP protein, human; D016708:Synaptophysin