Mitochondrial function is depressed acutely following traumatic brain injury
Abstract
Following a traumatic brain injury (TBI), the risk for seizure development increases. Post-traumatic epilepsy (PTE) is defined as continual seizures in the weeks-months following injury and are correlated with the extent of neurodegeneration. A full understanding of the pathways that lead to development and progression of PTE remains a priority, as TBI induced epileptogenesis may account for up to 20% of the epileptic population. Mitochondria function is known to be compromised following TBI and lead to increased tissue damage and cognitive deficits. The goal of this project is to determine if mitochondrial energetics are altered during the epileptogenic process following TBI in both the acute and chronic phases. Mice underwent controlled cortical impact injury (or sham) surgery to induce TBI and mitochondrial function was analyzed across three acute timepoints (2h, 24h, and 72h). Mitochondria was isolated from both ipsilateral and contralateral cerebral and hippocampus. The mitochondria were then put through the O2k-Fluorespirometer and stimulated with various substrates to analyze the electron transport chain. TBI mitochondria generally showed impaired respiration and decreased ADP phosphorylation. This is indicative of impaired ATP production. This result was particularly marked at 2h post injury. Respiration through both mitochondrial Complex I (glutamate/malate) and Complex II (succinate) tended to decrease, especially in the ipsilateral hemisphere, suggested that during the acute phase mitochondrial function is depressed. As a result, it can be inferred that the TBI decreased mitochondrial efficiency overall, but 2h post-TBI mice could be the most susceptible to seizures due to the severity of the injury. This marked decrease at 2h suggests that early intervention strategies targeting mitochondrial function may have the best efficacy. Further work is ongoing to investigate the cell signaling involved in this acute phase as well as determining if there are mitochondrial deficits chronically that increase seizure susceptibility.
Start Time
16-4-2025 1:30 PM
End Time
16-4-2025 4:00 PM
Presentation Type
Poster
Presentation Category
Science, Technology and Engineering
Student Type
Graduate Student - Doctoral
Faculty Mentor
Chad Frasier
Faculty Department
Biomedical Sciences
Mitochondrial function is depressed acutely following traumatic brain injury
Following a traumatic brain injury (TBI), the risk for seizure development increases. Post-traumatic epilepsy (PTE) is defined as continual seizures in the weeks-months following injury and are correlated with the extent of neurodegeneration. A full understanding of the pathways that lead to development and progression of PTE remains a priority, as TBI induced epileptogenesis may account for up to 20% of the epileptic population. Mitochondria function is known to be compromised following TBI and lead to increased tissue damage and cognitive deficits. The goal of this project is to determine if mitochondrial energetics are altered during the epileptogenic process following TBI in both the acute and chronic phases. Mice underwent controlled cortical impact injury (or sham) surgery to induce TBI and mitochondrial function was analyzed across three acute timepoints (2h, 24h, and 72h). Mitochondria was isolated from both ipsilateral and contralateral cerebral and hippocampus. The mitochondria were then put through the O2k-Fluorespirometer and stimulated with various substrates to analyze the electron transport chain. TBI mitochondria generally showed impaired respiration and decreased ADP phosphorylation. This is indicative of impaired ATP production. This result was particularly marked at 2h post injury. Respiration through both mitochondrial Complex I (glutamate/malate) and Complex II (succinate) tended to decrease, especially in the ipsilateral hemisphere, suggested that during the acute phase mitochondrial function is depressed. As a result, it can be inferred that the TBI decreased mitochondrial efficiency overall, but 2h post-TBI mice could be the most susceptible to seizures due to the severity of the injury. This marked decrease at 2h suggests that early intervention strategies targeting mitochondrial function may have the best efficacy. Further work is ongoing to investigate the cell signaling involved in this acute phase as well as determining if there are mitochondrial deficits chronically that increase seizure susceptibility.