Minocycline treatment timing and its influence on serotonin expression following spinal cord injury

Abstract

The effects of incomplete traumatic spinal cord injury (SCI) can be partly reversed by the plasticity of local and spared descending projections. A promising window of plasticity occurs for a number of weeks following injury and involves the control of neuroinflammatory processes. The FDA-approved drug, minocycline, is a promising drug for treating SCI since it decreases microglia activity, reduces macrophage activity, and generally provides neuroprotective properties. In this thesis I established a timeline of injury, looking at both serotonin (5-HT) and microglia/macrophage (Iba-1) immunoreactivity (ir), and I targeted a time point before a significant reduction of descending serotonergic fibers, in the form of 5-HTir, took place (i.e. 1-week). I found that the administration of minocycline increased 5-HTir caudal and ipsilateral to the lesion, compared to shams and controls. Using the selected time point, 1-week post-SCI, I administered minocycline and found a decrease in lesion size and an increase of 5-HTir both caudal and ipsilateral to the injury as well as rostral and contralateral to the injury. In this thesis, I provide evidence that minocycline impacts 5-HT expression when administered acutely and one week following SCI. These data suggest that the timing of minocycline treatment influences the neuroprotective properties previously reported and also influences descending 5-HT expression post-SCI.