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

Spinal cord injury (SCI) can result in significant neurological impairment and functional and cognitive deficits. It is well established that SCI results in focal neurodegeneration that gradually spreads to other cord areas. On the other hand, traumatic brain injury (TBI) is strongly associated with...

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Bibliographic Details
Published in:Molecular neurobiology 2022-07, Vol.59 (7), p.4197-4208
Main Authors: Nakhjiri, Elnaz, Roqanian, Shaqayeq, Zangbar, Hamid Soltani, Seyedi Vafaee, Manuchehr, Mohammadnejad, Daryoush, Ahmadian, Shahin, Zamanzadeh, Selva, Ehsani, Ehsan, Shahabi, Parviz, Shahpasand, Koorosh
Format: Article
Language:English
Subjects:
Animal models
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cell death
Cerebrospinal fluid
Cognitive ability
Electron microscopy
Immunoblotting
Immunological memory
Immunotherapy
Memory
Mitochondria
Monoclonal antibodies
Neurobiology
Neurodegeneration
Neurodegenerative diseases
Neurological complications
Neurology
Neurosciences
Pathology
Spatial memory
Spinal cord injuries
Tau protein
Traumatic brain injury
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Summary:Spinal cord injury (SCI) can result in significant neurological impairment and functional and cognitive deficits. It is well established that SCI results in focal neurodegeneration that gradually spreads to other cord areas. On the other hand, traumatic brain injury (TBI) is strongly associated with tau protein pathology and neurodegeneration that can spread in areas throughout the brain. Tau is a microtubule-associated protein abundant in neurons and whose abnormalities result in neuronal cell death. While SCI and TBI have been extensively studied, there is limited research on the relationship between SCI and brain tau pathology. As a result, in this study, we examined tau pathology in spinal cord and brain samples obtained from severe SCI mouse models at various time points. The effects of severe SCI on locomotor function, spatial memory, anxiety/risk-taking behavior were investigated. Immunostaining and immunoblotting confirmed a progressive increase in tau pathology in the spinal cord and brain areas. Moreover, we used electron microscopy to examine brain samples and observed disrupted mitochondria and microtubule structure following SCI. SCI resulted in motor dysfunction, memory impairment, and abnormal risk-taking behavior. Notably, eliminating pathogenic cis P-tau via systemic administration of appropriate monoclonal antibodies restored SCI’s pathological and functional consequences. Thus, our findings suggest that SCI causes severe tauopathy that spreads to brain areas, indicating brain dysfunction. Additionally, tau immunotherapy with an anti- cis P-tau antibody could suppress pathogenic outcomes in SCI mouse models, with significant clinical implications for SCI patients. Graphical abstract SCI induces profound pathogenic cis p-tau, which diffuses into the brain through CSF, resulting in brain neurodegeneration and cognitive decline.
ISSN:0893-7648
1559-1182
DOI:10.1007/s12035-022-02843-1