Following a traumatic brain injury (TBI), the neocortex undergoes time-dependent cellular responses including immediate tissue deformation, enhanced excitability and elevated expression of immediate early genes. However, the spatial extent of early neuronal activity after a focal injury remains unclear. Here we use Targeted Recombination in Active Populations (TRAP) reporter mice of both sexes to identify neurons activated in the acute phase following a controlled cortical impact injury applied to somatosensory neocortex. We find widespread cell activation across large portions of the cortex that extends beyond the astrocytic and microglial responses marking the injury site. Activated cells are predominantly neurons, and few cells co-label with GFAP or IBA1. Our findings reveal that even focal injury engages cortical circuits across large portions of the injured brain, highlighting the importance of considering cortex-wide neuronal dynamics in the early post-injury period and their potential impact on network excitability, remodeling and recovery. Significance Statement Traumatic brain injury leads to increased expression of immediate early genes, which are commonly used as surrogate markers of cell activity, but the spatial extent of early neuron activation remains unresolved. Here, using a transgenic reporter mouse line, we show that focal contusion injury leads to an activation of neurons across large portions of the ipsilateral neocortex that extends well beyond the lesion area. These findings show the whole injured hemisphere becomes engaged in the early response to focal injury, suggesting cortex-wide neuronal dynamics in the early post-injury period may influence network excitability and recovery.
Tierno et al. (Fri,) studied this question.