Headbutting goats self-inflict traumatic brain injury

Abstract

Traumatic brain injury (TBI) is a characteristic feature of neurodegenerative diseases such as Alzheimers disease and chronic traumatic encephalopathy. Small animal models have been used to establish clinically relevant biomarkers of neuropathology, however, they show significant anatomical differences from humans and are affected by artificial experimental manipulations, making them often unsuitable for longitudinal study of repetitive mild TBI. There is a need for more diverse and translationally relevant animal models to better understand disease onset and development. Building on a previous study of neuropathology in headbutting bovids in the wild, this pilot study investigated whether freely headbutting domestic goats, which naturally engage in low-intensity, high-frequency head impacts, accumulate measurable biomarkers of neurodegeneration in cerebrospinal fluid (CSF) and brain tissue. Over a six-month period, three male goats (Capra hircus) were allowed to freely headbutt under continuous video surveillance. Monthly CSF samples were collected, and concentrations of key neurodegeneration biomarkers were measured via multiplex immunoassays, including amyloid-{beta} peptides (A{beta}40, A{beta}42), total and phosphorylated tau (tTau and pTau), glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B), and neurofilament M (NF-M). Imaging studies were completed for non-invasive assessment of glucose metabolism ([18F]-FDG) and neuroinflammation via translocator protein (TSPO, [18F]DPA-714). Postmortem immunohistochemistry was conducted on prefrontal cortical tissues using antibodies targeting pTau, GFAP, and S100B. Head impact kinematics were quantified using horn-mounted accelerometer and inclinometer sensors that recorded linear acceleration, rotational velocity, and head orientation during naturally occurring headbutting events. Several notable trends were observed. Phosphorylated tau as well as reactive astrocytes were detected in the brain tissue, mirrored by elevated GFAP detected in the CSF. PET TSPO did not illustrate a significant signal, however, PET FDG revealed frontal-dominant activity in all goats, and one with asymmetrical activation. Overall, the goats sustained 5,000-7,000 head impacts each over six months. Accelerometer measurements recorded forces up to 388 N and peak acceleration up to 16.5 g. This multi-modal observational study is the first to characterize neurodegeneration biomarkers and kinematics in headbutting goats. Even at one year old, the combination of pTau and gliosis in both the brain tissue and CSF indicates that the goats repetitive head impacts begin to show neurodegenerative consequences early in life. Likely, the severity of these consequences increases with headbutts and age, eventually resulting in chronic neurodegeneration. This system shows promise as a large-animal model for the longitudinal study of the onset and progression of neurodegenerative disease.