title: Ultrastructure of Diaschisis Lesions after Traumatic Brain Injury.
abstract: We used controlled cortical impact in mice to model human traumatic brain injury (TBI). Local injury was accompanied by distal diaschisis lesions that developed within brain regions anatomically connected to the injured cortex. At 7 days after injury, histochemistry documented broadly distributed lesions, particularly in the contralateral cortex and ipsilateral thalamus and striatum. Reactive astrocytosis and microgliosis were noted in multiple neural pathways that also showed silver-stained cell processes and bodies. Wisteria floribunda agglutinin (WFA) staining, a marker of perineuronal nets, was substantially diminished in the ipsilateral, but less so in the contralateral cortex. Contralateral cortical silver positive diaschisis lesions showed loss of both phosphorylated and unphosphorylated neurofilament staining, but overall preservation of microtubule-associated protein (MAP)-2 staining. Thalamic lesions showed substantial loss of MAP-2 and unphosphorylated neurofilaments in addition to moderate loss of phosphorylated neurofilament. One animal demonstrated contralateral cerebellar degeneration at 7 days post-injury. After 21 days, the gliosis had quelled, however persistent silver staining was noted. Using a novel serial section technique, we were able to perform electron microscopy on regions fully characterized at the light microscopy level. Cell bodies and processes that were silver positive at the light microscopy level showed hydropic disintegration consisting of: loss of nuclear heterochromatin; dilated somal and neuritic processes with a paucity of filaments, tubules, and mitochondria; and increased numbers of electron-dense membranous structures. Importantly the cell membrane itself was still intact 3 weeks after injury. Although the full biochemical nature of these lesions remains to be deciphered, the morphological preservation of damaged neurons and processes raises the question of whether this is a reversible process.
authors.affiliation: 1 Department of Pathology, University of Pittsburgh , Pittsburgh, Pennslyvania.
authors.forename: Clayton A
authors.initials: CA
authors.lastname: Wiley
authors.affiliation: 1 Department of Pathology, University of Pittsburgh , Pittsburgh, Pennslyvania.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Bissel
authors.affiliation: 1 Department of Pathology, University of Pittsburgh , Pittsburgh, Pennslyvania.
authors.forename: Andrew
authors.initials: A
authors.lastname: Lesniak
authors.affiliation: 2 VA Pittsburgh Healthcare System and Safar Center for Resuscitation Research , Pittsburgh, Pennsylvania.|3 Department of Neurosurgery, Anesthesiology, Physical Medicine, University of Pittsburgh , Pittsburgh, Pennslyvania.
authors.forename: C Edward
authors.initials: CE
authors.lastname: Dixon
authors.affiliation: 4 Center for Biologic Imaging, University of Pittsburgh , Pittsburgh, Pennslyvania.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Franks
authors.affiliation: 4 Center for Biologic Imaging, University of Pittsburgh , Pittsburgh, Pennslyvania.
authors.forename: Donna
authors.initials: D
authors.lastname: Beer Stolz
authors.affiliation: 4 Center for Biologic Imaging, University of Pittsburgh , Pittsburgh, Pennslyvania.
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.affiliation: 1 Department of Pathology, University of Pittsburgh , Pittsburgh, Pennslyvania.
authors.forename: Guoji
authors.initials: G
authors.lastname: Wang
authors.affiliation: 5 NeuroScience Associates , Knoxville, Tennessee.
authors.forename: Robert
authors.initials: R
authors.lastname: Switzer
authors.affiliation: 2 VA Pittsburgh Healthcare System and Safar Center for Resuscitation Research , Pittsburgh, Pennsylvania.|3 Department of Neurosurgery, Anesthesiology, Physical Medicine, University of Pittsburgh , Pittsburgh, Pennslyvania.|6 Department of Pediatrics, and Rehabilitation and Critical Care Medicine, University of Pittsburgh , Pittsburgh, Pennslyvania.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
authors.affiliation: 1 Department of Pathology, University of Pittsburgh , Pittsburgh, Pennslyvania.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Murdoch
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology* / Q000648:ultrastructure*; D000070642:Brain Injuries, Traumatic / Q000473:pathology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL
keywords: TBI; axonal injury; controlled cortical impact; electron microscopy; light microscopy