Single episode of moderate to severe traumatic brain injury leads to chronic neurological deficits and Alzheimer's-like pathological dementia

Kumar Vaibhav; Mayuri Gulhane; Pankaj Ahluwalia; Manish Kumar; Meenakshi Ahluwalia; Ashiq M Rafiq; Vibha Amble; Manuela G Zabala; Jacob B Miller; Liam Goldman; Ashis K Mondal; Ferenc Deak; Ravindra Kolhe; Ali S Arbab; Fernando L Vale

doi:10.1007/s11357-024-01183-3

Single episode of moderate to severe traumatic brain injury leads to chronic neurological deficits and Alzheimer's-like pathological dementia

Geroscience. 2024 May 11. doi: 10.1007/s11357-024-01183-3. Online ahead of print.

Authors

Kumar Vaibhav^{1

2}, Mayuri Gulhane³, Pankaj Ahluwalia⁴, Manish Kumar^{3

5}, Meenakshi Ahluwalia^{3

4

6}, Ashiq M Rafiq⁷, Vibha Amble⁸, Manuela G Zabala⁸, Jacob B Miller^{7

9}, Liam Goldman³, Ashis K Mondal⁴, Ferenc Deak⁷, Ravindra Kolhe⁴, Ali S Arbab⁶, Fernando L Vale³

Affiliations

¹ Brain Injury, Senescence, and Translational Neuroscience Lab, Department of Neurosurgery, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA. kvaibhav@augusta.edu.
² Transdisciplinary Research Initiative in Inflammaging and Brain Aging (TRIBA), Augusta University, Augusta, GA, USA. kvaibhav@augusta.edu.
³ Brain Injury, Senescence, and Translational Neuroscience Lab, Department of Neurosurgery, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA.
⁴ Department of Pathology, Medical College of Georgia, Augusta University, Augusta, GA, USA.
⁵ Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.
⁶ Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, GA, USA.
⁷ Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA.
⁸ Center for Undergraduate Research Studies, Augusta University, Augusta, GA, USA.
⁹ The Graduate School, Augusta University, Augusta, GA, USA.

PMID: 38733547
DOI: 10.1007/s11357-024-01183-3

Abstract

Traumatic brain injury (TBI) is one of the foremost causes of disability and mortality globally. While the scientific and medical emphasis is to save lives and avoid disability during acute period of injury, a severe health problem can manifest years after injury. For instance, TBI increases the risk of cognitive impairment in the elderly. Remote TBI history was reported to be a cause of the accelerated clinical trajectory of Alzheimer's disease-related dementia (ADRD) resulting in earlier onset of cognitive impairment and increased AD-associated pathological markers like greater amyloid deposition and cortical thinning. It is not well understood whether a single TBI event may increase the risk of dementia. Moreover, the cellular signaling pathways remain elusive for the chronic effects of TBI on cognition. We have hypothesized that a single TBI induces sustained neuroinflammation and disrupts cellular communication in a way that results later in ADRD pathology. To test this, we induced TBI in young adult CD1 mice and assessed the behavioral outcomes after 11 months followed by pathological, histological, transcriptomic, and MRI assessment. On MRI scans, these mice showed significant loss of tissue, reduced CBF, and higher white matter injury compared to sham mice. We found these brains showed progressive atrophy, markers of ADRD, sustained astrogliosis, loss of neuronal plasticity, and growth factors even after 1-year post-TBI. Because of progressive neurodegeneration, these mice had motor deficits, showed cognitive impairments, and wandered randomly in open field. We, therefore, conclude that progressive pathology after adulthood TBI leads to neurodegenerative conditions such as ADRD and impairs neuronal functions.

Keywords: Alzheimer’s disease-related dementia (ADRD); Cognitive impairment; Neuropathology; Synapse; TBI; White matter injury.

Abstract

Grants and funding