Spinal Cord Injury Causes Prominent Tau Pathology Associated with Brain Post-Injury Sequela

Abstract Spinal cord injury (SCI) can lead to neurological impairment with significant functional and cognitive deficits. It is obvious that SCI causes focal neurodegeneration that gradually expands to the other cord areas. On the other hand, it is clear that traumatic brain injuries result in tau protein pathology and profound neurodegeneration. Tau is a microtubule-associated protein, which is highly expressed in neurons, and its abnormalities result in neuronal cell death. Moreover, it is clear that tau pathology spreads in various brain areas upon trauma. Therefore, we herein examined tau pathology in the spinal cord as well as brain samples at various time-points in severe SCI mouse models. We examined the effects of severe SCI on locomotor function, spatial memory, and anxiety/risk-taking behavior. We found a gradual increased tau pathology in the spinal cord as well as brain areas; confirmed by immunostaining and immunoblotting. Moreover, we studied the brain samples with electron microscopy and observed disrupted mitochondria and microtubule structure upon SCI. SCI caused motor dysfunction, memory impairment, and abnormal risk-taking behavior. Importantly, pathogenic cis P-tau elimination with systemic administration of respective monoclonal antibody restored SCI-related pathological and functional consequences. Thus, our finding suggests that SCI results in profound tauopathy, which spreads to brain areas, reflecting brain dysfunction. Moreover, tau immunotherapy with anti- cis P-tau antibody could suppress the pathogenic outcomes in the SCI mouse models, which would have profound clinical implications in the SCI patients.