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Axonal Damage due to Traumatic Brain Injury

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Handbook of Neurochemistry and Molecular Neurobiology

Abstract:

Shearing motions during head injury often result in damage to axons scattered throughout the brain parenchyma. Although diffuse axonal injury (DAI) is thought to be a major contributor to morbidity after traumatic brain injury, no clinically approved treatment strategies are currently available to target dysfunctional or axotomized axons. Here, histological and imaging methods for detecting traumatic axonal injury (TAI) are reviewed, along with experimental models that have been developed to study the relationship between mechanical deformation and axonal injury. Data from clinical and experimental studies are summarized, which describe acute and progressive alterations in the myelin sheath and the axolemma, including modifications of axolemma permeability characteristics and membrane-bound proteins. The cytoskeleton is markedly affected by TAI, as evidenced by disruption of both neurofilament and microtubule networks and impairment of axonal transport. Several studies have demonstrated a role for calpains in posttraumatic axonal damage, while evidence for activity of other proteases is more preliminary. To date, most experimental studies exploring treatment strategies for TAI have focused on either the inhibition of mitochondrial permeability transition or the attenuation of axonal pathology through hypothermia. These studies and other novel approaches are reviewed. In closing, recent developments in methodologies for assessing axonal injury are outlined and opportunities for future investigations are suggested.

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Abbreviations

APP:

β-amyloid precursor protein

CCI:

controlled cortical impact

CNS:

central nervous system

CsA:

cyclosporin A

CT:

computerized tomography

DAI:

diffuse axonal injury

FP:

fluid percussion injury

GCS:

Glasgow Coma Scale

GOS:

Glasgow Outcome Scale

HRP:

horseradish peroxidase

MRI:

magnetic resonance imaging

MRS:

magnetic resonance spectroscopy

NFH:

neurofilament protein heavy subunit

NFL:

neurofilament protein light subunit

NFM:

neurofilament protein medium subunit

TAI:

traumatic axonal injury

TBI:

traumatic brain injury

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Acknowledgments

The authors thank Heather N. Foozer for assistance in manuscript preparation. This work was supported by NIH R01 NS045131, KSCHIRT 6-12, and T32 NS043126.

Authors
  1. K. E. Saatman
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  2. G. Serbest
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  3. M. F. Burkhardt
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Editor information

Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 10962, 140 Old Orangeburg Road, Orangeburg, New York, USA

    Abel Lajtha (Director) (Director)

  2. Department of Neurosciences Division of Neurology, Medical University of South Carolina, 29425, 96 Jonathan Lucas Street, Suite 309, Charleston, SC, USA

    Naren Banik

  3. Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, 29209, 6439 Garners Ferry Road Building 2, Room C11, Columbia, SC, USA

    Swapan K. Ray

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Saatman, K.E., Serbest, G., Burkhardt, M.F. (2009). Axonal Damage due to Traumatic Brain Injury. In: Lajtha, A., Banik, N., Ray, S.K. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30375-8_16

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