Projects
Studying the Effects of Secondary Injury on TBI Pathophysiology and Biology
Our lab is interested in the effects of secondary injury on TBI pathophysiology and biology. By leveraging the optic nerve as a model of TBI-induced axonal injury, we hope to better understand the mechanisms that govern secondary injury cascades. By determining which pathways are important, and how they interact we can provide better insight into how long-term outcomes develop and potential ways to prevent them.
Lab Projects
Chronic Traumatic Optic Neuropathy (TON) Outcomes and Mechanisms of Injury Resilience
TON is an important source of vision loss after blunt head trauma, and results in optic nerve atrophy, loss of retinal ganglion cells, and loss of visual function. The long-term pathophysiology of TON is not yet well understood. We have found that there is ongoing degeneration and gliosis in optic nerve and optic tract after TON, and at early chronic time points (30 days) there is reactivation of endoplasmic reticulum stress pathways. We have also found that some individuals have reduced axonal degeneration and others have increased axonal degeneration. Because of this bimodal finding in our groups, we plan to analyze what makes these separate populations unique to identify potential mechanisms of resilience.
Image from our 2021 publication in Cells, we found that some individuals appear to be more resilient to injury than others. (E) Also highlights a common histological stain using FluoroJade-B to identify degenerating axons in the optic tract.
ER Stress and Oxidative Stress Mechanistic Studies
Endoplasmic reticulum (ER) stress is a cellular stress response that is activated in order to cope with cellular homeostatic challenges. In early or mild activations, ER stress is protective. However, with prolonged or severe challenges, ER stress can cause apoptotic cell death. Additionally, there is a significant role for oxidative stress, and these two stress pathways highly overlap. Thus, we are interested in understanding their relationship after TBI and whether interfering with certain aspects of this relationship might prove more beneficial than targeting only one process.
Understanding the Role of Systemic Inflammation in TON/TBI Outcomes
TON triggers inflammation at the injury site, leading to degeneration and death of nerve cells in the eye and optic nerve. Head trauma also leads to systemic (i.e., in the whole body) inflammation, which we have found likely plays a role in secondary injury to the optic nerves. Ongoing research in the lab seeks to find ways to alter this inflammation to improve outcomes after optic nerve trauma.
A major source of Reactive Oxygen Species (ROS) after injury is mitochondria, which release superoxide ions. Here, we show labeled superoxide in the optic nerve. The light blue arrow points to an axon, and the light purple circle surrounds a myelinating oligodendrocyte, inside both of which we can see high levels of mitochondrial superoxide. This image was taken on one of Cincinnati Children's super resolution Nikon microscopes in our Confocal Imaging Core.
Determining the Influence of Chronic Stress on TBI Outcomes
Adolescence represents a critical period of increased vulnerability to stress, which increases in chronic illnesses such as TBI. We are interested in the effect of chronic stress on brain pathology after head trauma. Because axonal degeneration after TBI is associated with glial cell activation, we also focus on how microglial and astrocyte functions are chronically altered after TBI.
Our lab is interested in the effects of secondary injury on TBI pathophysiology and biology. By leveraging the optic nerve as a model of TBI-induced axonal injury, we hope to better understand the mechanisms that govern secondary injury cascades. By determining which pathways are important, and how they interact we can provide better insight into how long-term outcomes develop and potential ways to prevent them.
We are now considering the phagocytic (“eat me”) role of glial cells after TBI. Here you can see the brain’s immune cells, microglia (IBA1), engulfing neuronal debris (CD68) and astrocytes (GFAP) doing the same thing by eating (LAMP2) in the optic tract after injury.
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