Life Sciences & Biotechnology
Title : | Neurological implications of traumatic brain injury – multiscale modeling of brain strain-induced Tau protein aggregation |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Harikrishnan Narayanan Unni, Indian Institute Of Technology (IIT) Hyderabad, Telangana |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | harikrishnan@iith.ac.in |
Details
Executive Summary : | Neuropathology in traumatic brain injury (TBI) is deeply linked to the biomechanical forces in the cerebral domain. Mechanical loading results in immediate deformations, resulting in axonal disruption, neuronal loss and release of neurotransmitters. Diffuse axonal injury (DAI) is severe type of concussion that affects the axonal tracts across white matter encephalon. Recent evidences suggest that the brain strain can induce aggregation of Tau protein in the neuronal-axonal space, and can result in neurodegeneration post-TBI. The link between the biomechanical strains and axonal damage leading to Tau aggregation is poorly understood. Multiscale computational models that link macroscopic brain strain with axonal damage and Tau aggregation can be really helpful in this regard. The idea of the proposal stems from the above considerations. We plan to use sophisticated FEM models of human brain to calculate brain strains resulting from TBI. Diffusion tensor images (DTI) images highlighting the axonal orientations will be employed, and an anisotropic hyperviscoelastic model will be used to represent the soft tissues. The axonal strain parameters thus calculated will be used to drive a computational biological model that represents the interaction of numerous cells and cytokines in the neuronal space. This model involves the solution of simultaneous differential equations, resulting in quantitative measures of Tau protein aggregation (Neurofibrillary tangle formation) and neuronal decline post-TBI. The proposed work includes a comprehensive multiscale model of neurodegeneration post-TBI, and could be useful for in-silico drug designs. |
Total Budget (INR): | 6,60,000 |
Organizations involved