Diffuse axonal injury (DAI) is a common and important pathological feature of traumatic brain injury (TBI), particularly affecting white matter axons due to mechanical forces during injury. DAI encompasses a range of effects from primary axonal damage to secondary physiological changes, leading to acute symptoms like loss of consciousness and chronic issues such as neurodegeneration. Recent evidence suggests that TBI can induce long-term neurodegenerative processes, including axonal pathology linked to Alzheimer's disease-like changes. DAI is characterized by axonal swelling, transport interruption, and Wallerian degeneration, and is often identified through histopathological examination or immunohistochemical techniques like APP staining. Advanced neuroimaging techniques such as diffusion tensor imaging (DTI) may help assess white matter integrity in vivo. DAI is primarily caused by rotational acceleration of the brain, leading to shear and tensile strains. Axonal trauma can result in primary or secondary axotomy, with implications for consciousness and cognitive function. Secondary chemical cascades, including mitochondrial dysfunction, oxidative stress, and neuroinflammation, contribute to axonal damage. Axonal injury may also contribute to the formation of amyloid-beta plaques and neurofibrillary tangles, linking TBI to neurodegenerative diseases like Alzheimer's. Understanding DAI's pathogenesis and mechanisms is crucial for developing therapeutic interventions for TBI and related neurodegenerative conditions.Diffuse axonal injury (DAI) is a common and important pathological feature of traumatic brain injury (TBI), particularly affecting white matter axons due to mechanical forces during injury. DAI encompasses a range of effects from primary axonal damage to secondary physiological changes, leading to acute symptoms like loss of consciousness and chronic issues such as neurodegeneration. Recent evidence suggests that TBI can induce long-term neurodegenerative processes, including axonal pathology linked to Alzheimer's disease-like changes. DAI is characterized by axonal swelling, transport interruption, and Wallerian degeneration, and is often identified through histopathological examination or immunohistochemical techniques like APP staining. Advanced neuroimaging techniques such as diffusion tensor imaging (DTI) may help assess white matter integrity in vivo. DAI is primarily caused by rotational acceleration of the brain, leading to shear and tensile strains. Axonal trauma can result in primary or secondary axotomy, with implications for consciousness and cognitive function. Secondary chemical cascades, including mitochondrial dysfunction, oxidative stress, and neuroinflammation, contribute to axonal damage. Axonal injury may also contribute to the formation of amyloid-beta plaques and neurofibrillary tangles, linking TBI to neurodegenerative diseases like Alzheimer's. Understanding DAI's pathogenesis and mechanisms is crucial for developing therapeutic interventions for TBI and related neurodegenerative conditions.