Histology of Brain Trauma and Hypoxia-Ischemia

Forensic pathologists encounter hypoxic-ischemic (HI) brain damage or traumatic brain injuries (TBI) on an almost daily basis. Evaluation of the findings guides decisions regarding cause and manner of death. When there are gross findings of brain trauma, the cause of death is often obvious. However, microscopic evaluation should be used to augment the macroscopic diagnoses. Histology can be used to seek evidence for TBI in the absence of gross findings, e.g., in the context of reported or suspected TBI. Estimating the survival interval after an insult is often of medicolegal interest; this requires targeted tissue sampling and careful histologic evaluation. Retained tissue blocks serve as forensic evidence and also provide invaluable teaching and research material. In certain contexts, histology can be used to demonstrate nontraumatic causes of seemingly traumatic lesions. Macroscopic and histologic findings of brain trauma can be confounded by concomitant HI brain injury when an individual survives temporarily after TBI. Here we review the histologic approaches for evaluating TBI, hemorrhage, and HI brain injury. Amyloid precursor protein (APP) immunohistochemistry is helpful for identifying damaged axons, but patterns of damage cannot unambiguously distinguish TBI from HI. The evolution of hemorrhagic lesions will be discussed in detail; however, timing of any lesion is at best approximate. It is important to recognize artifactual changes (e.g., dark neurons) that can resemble HI damage. Despite the shortcomings, histology is a critical adjunct to the gross examination of brains.