33 - Neuropathology of acute decompensation in high-energy blunt non-penetrating injury in the gyrencephalic brain (swine): A role for axonal pathology in the brain stem

Abstract Text: Traumatic brain injury after high-velocity objects strike the head is associated with acute decompensation of vitals and high mortality. We have shown before that such neuropathologies are complex and involve subarachnoid hemorrhages (SAH) and diffuse vascular and axonal lesions in various brain locations. Axonal pathologies appear as classic diffuse axonal injury (DAI), indistinguishable from the ones encountered in acceleration injuries. Acute decompensation after TBI has been classically attributed to dysregulated sympathetic activity secondary to disconnection and loss of inhibitory control but the mechanisms are still unclear.
Here we utilize a model of Yucatan miniature swine injured from non-perforating ballistic and explore clinicopathological correlates of acute decompensation and mortality, with emphasis on vascular and axonal pathologies in the brainstem. Animals (n=22) with stable or critical vitals were euthanized within 4 hours after injury. Paraffin-embedded brains were processed in serial sections for general anatomy (Nissl), vascular pathology (Masson’s trichrome) and axonal pathology (APP). Brain stems were divided into 6 standard planes covering 101 anatomical regions including both nuclei/gray matter regions and white matter bundles. Individual cases were taken for stereological analysis of DAI per region of interest (ROI) using the fractionator probe. The majority of cases have SAH. Diffuse axonal injury in the brain stem differs among regions, but some areas such as the cerebral peduncle and adjacent substantia nigra pars reticulata, as well as certain thalamic regions are most heavily affected. Preliminary analysis of 59 regions between critical cases (with vital sign deterioration; n=6) and non-critical cases (n=12) reveal significantly higher axonal pathology in critically injured animals (p < 0.0001). Burden of axonal and vascular pathology does not generally discriminate between critical and non-critical cases. In contrast, less severely impacted regions are more commonly associated with acute deterioration in vital signs. Top among such regions are the dorsal motor nucleus of the vagus nerve and the nucleus of tractus solitaries, brain stem centers of autonomic/cardiovascular control, where pathological burden differs by more than 6-fold between critical and non-critical cases. These findings suggest a highly differentiated role of DAI in critical outcomes in the course of acute blunt TBI that may have important clinical implications.

Keywords: Pig Brain, Ballistic, Blunt Trauma, Helmet, APP, Microbleed, Axonal Pathology, Brainstem, Vascular Pathology, Autonomic Function, Acute Mortality, Axonal Injury, Hemorrhages