Diffuse axonal injury in brain trauma: insights from alterations in neurofilaments

Abstract

Traumatic brain injury (TBI) from penetrating or closed forces to the cranium can result in a range of forms of neural damage, which culminate in mortality or impart mild to significant neurological disability. In this regard, diffuse axonal injury (DAI) is a major neuronal pathophenotype of TBI and is associated with a complex set of cytoskeletal changes. The neurofilament triplet proteins are key structural cytoskeletal elements, which may also be important contributors to the tensile strength of axons. This has significant implications with respect to how axons may respond to TBI. It is not known, however, whether neurofilament compaction and the cytoskeletal changes that evolve following axonal injury represent a component of a protective mechanism following damage, or whether they serve to augment degeneration and progression to secondary axotomy. Here we review the structure and role of neurofilament proteins in normal neuronal function. We also discuss the processes that characterize DAI and the resultant alterations in neurofilaments, highlighting potential clues to a possible protective or degenerative influence of specific neurofilament alterations within injured neurons. The potential utility of neurofilament assays as biomarkers for axonal injury is also discussed. Insights into the complex alterations in neurofilaments will contribute to future efforts in developing therapeutic strategies to prevent, ameliorate or reverse neuronal degeneration in the central nervous system (CNS) following traumatic injury.

Characterization of Early Pathological Tau Conformations and Phosphorylation in Chronic Traumatic Encephalopathy

“…Recently, we showed that PAD exposure is a mechanism by which tau can directly impair anterograde fast axonal transport (23, 24, 27), which could contribute to axonal dysfunction and eventually neurodegeneration (31, 64). Axonal dysfunction is a prominent feature of traumatic brain injury-related pathology and several lines of evidence from animal models, culture models, and human traumatic brain injury cases support a primary role for axonal dysfunction in posttraumatic neurodegeneration (65–68). In this study, we identified PAD-exposed tau, oligomeric tau, and phospho-S422 tau in the axonal pathologies of CTE.…”

Sulforaphane administration alleviates diffuse axonal injury (DAI) via regulation signaling pathway of NRF2 and HO‐1

“…[1][2][3][4] DAI is often accompanied by cytoskeletal alterations, such as the presence of varicosities and swellings along terminal bulbs and axons. [8][9][10] Furthermore, the elevated level of Ca2+ in the mitochondria can promote the synthesis of reactive oxygen species (ROS), thus increasing the levels of oxidative stress in axons. [8][9][10] Furthermore, the elevated level of Ca2+ in the mitochondria can promote the synthesis of reactive oxygen species (ROS), thus increasing the levels of oxidative stress in axons.…”

“…[5][6][7] Such cytoskeletal alterations may be induced by mechanical damages and subsequent Ca2+ influx through the disruptions in the axolemma. 10 In fact, oxidative stress can be induced by the disruption of the equilibrium between various biochemical processes, thus leading to dysfunction in nonenzymatic and enzymatic cellular defense systems against oxidation. 10 In fact, oxidative stress can be induced by the disruption of the equilibrium between various biochemical processes, thus leading to dysfunction in nonenzymatic and enzymatic cellular defense systems against oxidation.…”

Axonal Injury in the Lateral Geniculate Body: Radiological Diagnosis

“…congruous homonymous incomplete hemianopia ( Figure 1B), a finding that is consistent with axonal deterioration over a 6-month period. 9 Macular optical coherence tomography (OCT) showed atrophy of the ganglion cells in the right side of both maculae, indicating anterograde degeneration of the visual pathway (Figure 2). On the other hand, OCT of the optic disc showed atrophy of nerve fibres superiorly and inferiorly in both eyes and also nasally in the LE.…”