Unmyelinated axons show selective rostrocaudal pathology in the corpus callosum after traumatic brain injury

Reeves TM, Smith TL, Williamson JC, Phillips LL (2012) Unmyelinated axons show selective rostrocaudal pathology in the corpus callosum after traumatic brain injury. J Neuropathol Exp Neurol. 71:3:198-210. doi: 10.1097/NEN.0b013e3182482590. Abstract Axonal injury is consistently observed following traumatic brain injury (TBI). Prior research has extensively characterized the post-TBI response in myelinated axons. Despite evidence that unmyelinated axons comprise a numerical majority of cerebral axons, pathological changes in unmyelinated axons following TBI have not been systematically studied. To identify morphological correlates of functional impairment of unmyelinated fibers following TBI, we assessed ultrastructural changes in corpus callosum axons. Adult rats received moderate fluid percussion TBI, which produced diffuse injury with no contusion. Cross-sectional areas of 13,797 unmyelinated, and 3,278 intact myelinated axons were stereologically measured at survival intervals from 3 hours to 15 days post-injury. The mean caliber of unmyelinated axons was significantly reduced at 3 to 7 days, and recovered by 15 days, but the time course of this shrinkage varied among the genu, mid-callosum and splenium. Relatively large unmyelinated axons appeared to be particularly vulnerable. Injury-induced decreases in unmyelinated fiber density were also observed but they were more variable than caliber reductions. By contrast, no significant morphometric changes were observed in myelinated axons. The finding of a preferential vulnerability in unmyelinated axons has implications for current concepts of axonal responses following TBI and for development of specifically targeted therapies.