Plasma and Imaging Biomarker Changes Following Rotational and Contusional Models of Traumatic Brain Injury in Adolescent Pigs

Abstract

Given the heterogeneity of traumatic brain injury (TBI), the development of a therapeutic strategy has been difficult despite decades of research. To develop an accurate classification system to guide individualized treatment, new protein biomarkers of TBI have been studied. We explored if different subtypes of TBI have unique biomarker profiles and histological findings using four pig models of TBI: moderate rotational injury (100–110 r/s), mild rotational injury (85–95 r/s), moderate contusional injury (8–9 mm), and mild contusional injury (6–7 mm). Among these groups, we identified unique profile of plasma neurofilament light (NFL) and glial fibrillary acidic protein (GFAP): whereas moderate contusion animals had early peak of NFL (2–3 days) and GFAP (1 day), mild contusion animals had delayed peak of NFL (8 days) and GFAP (3 days). Diffusion tensor imaging analysis found reduced fractional anisotropy in corona radiata for contusional injured animals but rotational injured animals showed no significant changes compared to control animals. Histological analysis showed prominent vascular inflammation and axonal injury in the pericontusional cortex in contusional injured animals. In rotational injured animals, prominent axonal injury was found in perivascular white matter. Future studies for mechanistic underpinning of biomarker changes are needed to establish therapeutic targets, predict severity of injury, and determine clinical trial enrollment and therapeutic response.