Time course, in vivo imaging of brain cells is crucial to fully understand the progression of secondary cellular damage and recovery in murine models of injury. We have combined high-resolution gradient index lens technology with a model of diffuse axonal injury in rodents to enable repeated visualization of fine features of individual cells in three-dimensional space over several weeks. For example, we recorded changes in morphology in the same axons in the external capsule numerous times over 30 to 60 days, before and after induced traumatic brain injury. We observed the expansion of secondary injury and limited recovery of individual axons in this subcortical white matter tract over time. In another application, changes in microglial activation state were visualized in the penumbra region of mice before and after ischemia induced by middle carotid artery occlusion. The ability to collect a series of high-resolution images of cellular features of the same cells pre- and post-injury enables a unique opportunity to study the progression of damage, spontaneous healing, and effects of therapeutics in mouse models of neurodegenerative disease and brain injury.