Longitudinal in vivo monitoring of axonal integrity after brain injury

AbstractTraumatic brain injury-induced axonal degeneration leads to acute and chronic neuropsychiatric impairment, neuronal death, and accelerated neurodegenerative diseases of aging, including Alzheimer’s and Parkinson’s diseases. Thus, there is much interest in developing treatments that protect axons after injury. For this endeavor, extended comprehensive evaluation of axonal integrity in experimental systems is required to evaluate the efficacy of putative interventions in preclinical models. However, traditional histological tissue proccessing techniques are logistically prohibitive for assessments of long-term pathology. Here, we report a new method of longitudinally monitoring the functional activity of thalamocortical axons before and after injury in vivo in the same animal over an extended period of time. Specifically, we expressed an axonal-targeting genetically-encoded calcium indicator in the mouse dorsolateral geniculate nucleus and then recorded axonal activity patterns in the visual cortex in response to visual stimulation. We demonstrate the utility of this method for assessing in vivo aberrant axonal activity patterns after traumatic brain injury, as well as for evaluating the therapuetic efficacy of the neuroprotective P7C3-A20 pharmacologic agent in vivo. We found that P7C3-A20 treatment minimized most, but not all, of the pathological changes in axonal activity patterns after traumatic brain injury.