Traumatically induced reactive change as visualized through the use of monoclonal antibodies targeted to neurofilament subunits.
Reactive axonal change has long been recognized as a feature of traumatic brain injury. To date, the histological methods used to identify reactive axons have been of limited utility, and they have not provided insight into the initial intraaxonal event that triggers reactive change. In this investigation, monoclonal antibodies to the 68, 150, and 200 kilodalton (kD) neurofilament subunits have been used to follow the progression of reactive axonal change. Anesthetized rats and cats were subjected to moderate traumatic brain injury. One to 72 hours (h) postinjury, their brains were processed for the light (LM) and electron (EM) microscopic immunocytochemical visualization of the various neurofilament subunits. Although all of the chosen antibodies revealed some degree of immunoreactivity within the reactive axon, the 68 kD antibody revealed a dramatic increase in immunoreactivity following injury. Within one h of injury, intensely 68 kD-immunoreactive axonal segments were observed with LM, and parallel EM microscopic analyses demonstrated that this increased immunoreactivity was associated with an increased number of 68 kD-immunoreactive neurofilaments, the majority of which coursed in an axis parallel to the axon's course. Over 2-6 h postinjury, these 68 kD-immunoreactive filaments demonstrated increasingly disordered alignment in relation to the axon's long axis, withdrawing from the focus of injury while becoming encompassed by an expanding organelle cap. It is posited that this increased 68 kD immunoreactivity is associated with a traumatically-induced increase in subunit exchange which contributes to cytoskeletal dysfunction leading to organelle accumulation, focal swelling and ultimate axonal detachment.
Yaghmai
A
A
Department of Anatomy, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0709.
Povlishock
J
J
D000818:Animals; D000911:Antibodies, Monoclonal; D001369:Axons / Q000473:pathology / Q000648:ultrastructure; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D002415:Cats; D005260:Female; D007150:Immunohistochemistry; D007382:Intermediate Filaments / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000911:Antibodies, Monoclonal