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Unmyelinated axons show selective rostrocaudal pathology in the corpus callosum after traumatic brain injury.

ABSTRACT: Axonal injury is consistently observed after traumatic brain injury (TBI). Prior research has extensively characterized the post-TBI response in myelinated axons. Despite evidence that unmyelinated axons comprise a numerical majority of cerebral axons, pathologic changes in unmyelinated axons after TBI have not been systematically studied. To identify morphologic correlates of functional impairment of unmyelinated fibers after TBI, we assessed ultrastructural changes in corpus callosum axons. Adult rats received moderate fluid percussion TBI, which produced diffuse injury with no contusion. Cross-sectional areas of 13,797 unmyelinated and 3,278 intact myelinated axons were stereologically measured at survival intervals from 3 hours to 15 days after injury. The mean caliber of unmyelinated axons was significantly reduced at 3 to 7 days and recovered by 15 days, but the time course of this shrinkage varied among the genu, mid callosum, and splenium. Relatively large unmyelinated axons seemed to be particularly vulnerable. Injury-induced decreases in unmyelinated fiber density were also observed, but they were more variable than caliber reductions. By contrast, no significant morphometric changes were observed in myelinated axons. The finding of a preferential vulnerability in unmyelinated axons has implications for current concepts of axonal responses after TBI and for development of specifically targeted therapies.

SUBMITTER: Reeves TM

PROVIDER: S-EPMC3295246 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Unmyelinated axons show selective rostrocaudal pathology in the corpus callosum after traumatic brain injury.

Reeves Thomas M TM Smith Terry L TL Williamson Judy C JC Phillips Linda L LL

Journal of neuropathology and experimental neurology 20120301 3

Axonal injury is consistently observed after traumatic brain injury (TBI). Prior research has extensively characterized the post-TBI response in myelinated axons. Despite evidence that unmyelinated axons comprise a numerical majority of cerebral axons, pathologic changes in unmyelinated axons after TBI have not been systematically studied. To identify morphologic correlates of functional impairment of unmyelinated fibers after TBI, we assessed ultrastructural changes in corpus callosum axons. Ad ...[more]

PMID: 22318124

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Project description:Biophysically based computational models of nerve fibers are important tools for designing electrical stimulation therapies, investigating drugs that affect ion channels, and studying diseases that affect neurons. Although peripheral nerves are primarily composed of unmyelinated axons (i.e., C-fibers), most modeling efforts focused on myelinated axons. We implemented the single-compartment model of vagal afferents from Schild et al. (1994) (Schild JH, Clark JW, Hay M, Mendelowitz D, Andresen MC, Kunze DL. J Neurophysiol 71: 2338-2358, 1994) and extended the model into a multicompartment axon, presenting the first cable model of a C-fiber vagal afferent. We also implemented the updated parameters from the Schild and Kunze (1997) model (Schild JH, Kunze DL. J Neurophysiol 78: 3198-3209, 1997). We compared the responses of these novel models with those of three published models of unmyelinated axons (Rattay F, Aberham M. IEEE Trans Biomed Eng 40: 1201-1209, 1993; Sundt D, Gamper N, Jaffe DB. J Neurophysiol 114: 3140-3153, 2015; Tigerholm J, Petersson ME, Obreja O, Lampert A, Carr R, Schmelz M, Fransén E. J Neurophysiol 111: 1721-1735, 2014) and with experimental data from single-fiber recordings. Comparing the two models by Schild et al. (1994, 1997) revealed that differences in rest potential and action potential shape were driven by changes in maximum conductances rather than changes in sodium channel dynamics. Comparing the five model axons, the conduction speeds and strength-duration responses were largely within expected ranges, but none of the models captured the experimental threshold recovery cycle-including a complete absence of late subnormality in the models-and their action potential shapes varied dramatically. The Tigerholm et al. (2014) model best reproduced the experimental data, but these modeling efforts make clear that additional data are needed to parameterize and validate future models of autonomic C-fibers.NEW & NOTEWORTHY Peripheral nerves are primarily composed of unmyelinated axons, and there is growing interest in electrical stimulation of the autonomic nervous system to treat various diseases. We present the first cable model of an unmyelinated vagal nerve fiber and compare its ion channel isoforms and conduction responses with other published models of unmyelinated axons, establishing important tools for advancing modeling of autonomic nerves.

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Unmyelinated axons show selective rostrocaudal pathology in the corpus callosum after traumatic brain injury.

Publications

Unmyelinated axons show selective rostrocaudal pathology in the corpus callosum after traumatic brain injury.

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