Mechanisms of inflammatory response in secondary brain injury: a review of computational approaches, challenges, and future directions

Traumatic brain injury (TBI) and the resulting brain damage and dysfunction are one of the leading causes of death for individuals under 40 worldwide. TBI can occur due to any external force causing deformation in the brain, and it involves a complicated timeline of the initial mechanical damage followed by a subsequent inflammatory response. The details and extent of the effects of TBI on the brain are understudied; however, researchers have developed a vast array of experimental and computational models in order to investigate the complex physiological dynamics and interactions in TBI. This review summarizes the hallmarks of TBI, focusing on the inflammatory response mechanisms within the secondary injury and how they have been modeled computationally. Finally, we highlight potential areas of improvement for computational models of TBI to enhance their relevance for translational and clinical research.