A Forensic Pathologic Study of Diffuse Axonal Injury of Brain

Kwon, Tae Jung; Choi, Young Shik; Lee, Bong Woo; Kim, Yoo Hoon; Yang, Kyung Moo; Chung, Nak Eun; Choi, Byung Ha; Park, Hye Jin; Kim, Yi Suk; Choi, Cheul Ho; Kim, Dae joong; Park, Jeong Hyun; Shin, Eun Kyung

Abstract

Axonal swellings or retraction balls are the major histologic hallmark of diffuse axonal injury in craniocerebral trauma. However, traditional histologic methods have proven of limited use in identifying reactive axonal change early in the posttraumatic course. In the present study, we try to compare conventional histologic and immunohistochemical methods, and transmission electron microscopy for demonstrating axonal swellings in 18 cases of head trauma. Brain regions such as corpus callosum, cerebral cortex, and brain stem were examined with immunohistochemical markers for beta-Amyloid precursor protein (beta-APP), neurofilament, ubiquitin, and CD68. The result was as follows: In 2 out of 18 cases, eosiniophilic spheroid axon balls were demonstrated with hematoxylineosin stain. Ultrastructurally, the axon balls exhibited misalignment, clumping or loss of neurofilaments, and accumulation of organelles. The organelles consisted of mitochondria, dense membranous bodies, and SER. The overlying thin myelin sheath was distended. In 6 cases with no axonal swellings at the histologic section, electron microscopic examination revealed axonopathy as evidenced by disintegration of neurofilaments and aggregated organelles. Immunostaining with an antibody to beta-APP disclosed varying positive reaction in axonal swellings and axon balls, suggestive for injured axons. However, the axons which did not appear obviously swollen at short survival times disclosed beta-APP negativity. Our findings suggest that transmission electron microscopy was very useful to identify the early axonal events in the posttraumatic course, while the immunostain was of limited value. The pathogenesis of axonal swellings in injured axons was discussed.