Continuing axonal and vascular change following experimental brain trauma.

Abstract

The course of axonal and vascular change following trauma was investigated in an animal model of fluid-percussion brain injury. To assess axonal change, the anterograde transport of horseradish peroxidase in selected cerebral and cerebellar efferents was studied in cats that had sustained minor to moderate injuries and had survived the traumatic episode for periods ranging from several hours to several months. To assess vascular change, cats were equipped with cranial windows, which allowed for both the direct functional study of the pial vasculature following injury and the postmortem harvesting of the studied vessels for morphologic analyses. Following fluid-percussion brain injury, a subtle focal perturbation of the axon occurred, and over a 12 to 24 hour period, this perturbation became progressively severe, with the result that the axon swelled, separated from its distal segment, and thereby formed an enlarged reactive swelling. With continued survival, some swellings persisted intact, others degenerated, and others demonstrated a dramatic regenerative response. This regenerative response, characterized by regenerative sprouting and growth conelike outgrowths, persisted through all survival periods considered. Immediately following the induction of the fluid-percussion injury, the pial arterioles dilated, manifested morphologic change, and displayed functional abnormalities. These vascular abnormalities appeared mediated by an accelerated metabolism of arachidonate via cyclooxygenase, which results in the generation of oxygen radicals. Radicals, such as the superoxide anion, continue to be produced within the first hour following injury and thus, similar to the observed axonal responses, continue to contribute to the brain's response to trauma. Although these axonal and vascular changes do not appear to be causally related, they both appear as a continuum of the initial insult and may become interlinked should a secondary insult ensue.