title: The use of antibodies targeted against the neurofilament subunits for the detection of diffuse axonal injury in humans.
abstract: Axonal injury is a common feature of human traumatic brain injury. Typically, damaged axons cannot be recognized unless a patient survives the injury by at least 10-12 hours (h). Limitations associated with the use of the traditional silver methods have been linked with this inability to recognize early posttraumatic reactive axonal change. Recently, we reported that antibodies targeting the neurofilament subunits proved useful in recognizing early traumatically induced axonal change in traumatically brain-injured animals. Accordingly, in the present communication, we employed antibodies to detect at the light microscopic level the 68 kD Nf-L and 170-200 kD Nf-H neurofilament subunits in head-injured patients who survived the traumatic event for periods ranging from 6 h to 59 days. Antibodies targeting all of the above-described subunits revealed a progression of reactive axonal change. Antibodies to the 68 kD subunit proved most useful, as they were not complicated by concomitant immunoreactivity in surrounding nuclei and/or dendritic and somatic elements. These immunocytochemical strategies revealed, at 6 h postinjury, focally swollen axons which appeared intact. By 12 h, this focal swelling had progressed to disconnection, with the immunoreactive swelling undergoing further expansion over 1 week postinjury. These findings demonstrate the utility of the previously described immunocytochemical strategies for detecting reactive axonal change in brain-injured humans, particularly in the early posttraumatic course. More importantly, these methods also demonstrate in humans that reactive axonal change is not necessarily caused by traumatically induced tearing.
authors.affiliation: Department of Neurosurgery, University of Washington, Seattle.
authors.forename: M S
authors.initials: MS
authors.lastname: Grady
authors.forename: M R
authors.initials: MR
authors.lastname: McLaughlin
authors.forename: C W
authors.initials: CW
authors.lastname: Christman
authors.forename: A B
authors.initials: AB
authors.lastname: Valadka
authors.forename: C L
authors.initials: CL
authors.lastname: Fligner
authors.forename: J T
authors.initials: JT
authors.lastname: Povlishock
mesh_terms: D000058:Accidental Falls; D000063:Accidents, Traffic; D000328:Adult; D000368:Aged; D000906:Antibodies; D001344:Autopsy; D001369:Axons / Q000648:ultrastructure*; D001921:Brain / Q000473:pathology*; D001930:Brain Injuries / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D046911:Macromolecular Substances; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000032:analysis* / Q000276:immunology
chemical_list: D000906:Antibodies; D046911:Macromolecular Substances; D016900:Neurofilament Proteins