| dc.description.abstract | The inflammatory response within the brain and spinal cord is a key biological response to disease, infection, and injury. Chronic pain and blast-induced traumatic brain injury (bTBI) are negatively impacted by the role of inflammation in response to acute injury triggers. Central nervous system (CNS) glia, specifically microglia and astrocytes, are key regulators of the immune signaling response that drive beneficial or detrimental cellular adaptations of inflammation. While directed energies, such as induced-heat or pressure, are recognized for their roles in modulating the impact of chronic pain and bTBI, their influence on pro-inflammatory signaling and the primary immune cell, microglia, remains unclear. Further investigation of glial responses to directed energies is crucial for the identification of relevant treatments for chronic pain and bTBI. This dissertation seeks to uncover the impact of laser-based directed energies, specifically photothermal and photomechanical effects, on CNS glial function and corresponding inflammatory signaling. The core of this work used intracellular calcium imaging to assess changes in cell physiology and used protein quantification techniques to measure inflammatory immune signaling in response to photothermal and photomechanical stimuli. Photothermal effects were found to induce multiple, distinct calcium transients in cultured microglia that were unrelated to necrosis or apoptosis. Furthermore, microglial pro-inflammatory immune signaling responded differently to photothermal stimuli depending on their initial physiological state, which uncovered a novel potential application of laser-based heating for chronic pain prevention. Photomechanical stimuli, similar to the initial pressure spike component of blasts, induced calcium transients in primary monocultures of microglia, astrocytes, and neurons. Microglial immune signaling indicated an early neuroprotective response to pressure exposure, while neurons were preferentially susceptible to photomechanical damage; suggesting that the pro-inflammatory response of bTBI may be driven by glial responses to neuronal damage rather than the initial pressure spike of blasts. | |
