Title : Ferritin and Neurotoxicity: A contributor to deleterious outcomes for Subarachnoid Hemorrhage
Ferritin is a protein that is critical for storing iron. Ferritin has recently been shown to play a role in iron homeostasis, immunomodulation, inflammation, and antioxidation. Previously, it was believed that ferritin was exclusively an intracellular peptide. However, there is significant evidence that ferritin is also in the serum, cerebral spinal fluid, and synovial fluid.
Within the brain, ferritin can bind to oligodendrocytes adjacent to the blood-brain-barrier to allow a docking point for ferritin to be engulfed by microglia in the brain parenchyma. When iron supplies in the brain are low, the lysosomal-autophagy pathway is activated to degrade ferritin and mobilize iron. Iron is critical in the brain for the formation of myelin and used during cellular respiration. If this sequestration and degradation of iron is impaired, the oxidative effects of iron may leave the brain vulnerable to neurotoxic effects. Subarachnoid hemorrhage (SAH) causes hemolysis of erythrocytes leading to the release of iron. Subsequently, a rise in ferritin is observed which promotes the neurologic insult following SAH. The degree to which ferritin is elevated post-SAH may correlate with the downstream neurotoxicity.
The literature seems to point to a critical balance in ferritin levels. Ferritin is protective against further oxidative effects of iron, but ferritin also contributes to neurotoxic outcomes. In this review, we will discuss the role of ferritin in the brain. Specifically, we will address cerebral ferritin iron uptake and ferritin clearance. This homeostatic process influences the development and progression of subarachnoid hemorrhage.
Audience Take Away:
- How ferritin contributes to neurotoxicity
- The role of microglia in vasospasm development
- Neuroinflammation and subarachnoid hemorrhage expansion
Brandon Lucke-Wold was born and raised in Colorado Springs, CO. He graduated magna cum laude with a BS in Neuroscience and distinction in honors from Baylor University. He completed his MD/PhD, Master’s in Clinical and Translational Research, and the Global Health Track at West Virginia University School of Medicine. His research focus was on traumatic brain injury, neurosurgical simulation, and stroke. At West Virginia University, he also served as a health coach for the Diabetes Prevention and Management program in Morgantown and Charleston, WV, which significantly improved health outcomes for participants. In addition to his research and public health projects, he is a co-founder of the biotechnology company Wright-Wold Scientific, the pharmaceutical company CTE cure, and was a science advocate on Capitol Hill through the Washington Fellow’s program.
He has also served as president of the WVU chapters for the American Association of Pharmaceutical Scientists, Neurosurgery Interest group, and Erlenmeyer Initiative Entrepreneur group. In addition, he has served as vice president for the graduate student neuroscience interest group, Nu Rho Psi Honor Society, and medical students for global health. He was an active member of the Gold Humanism Honor Society and Alpha Omega Alpha Honor Society. He is currently a member of the UF House Staff Council, Positive Culture Committee, Quality Improvement Committee, Board of Directors Alachua County Medical Society, and Accreditation Requirements Review Committee. He is married to Noelle Lucke-Wold and has two children. As a family, they enjoy running with their dogs, rock climbing, and traveling. In his spare time, Brandon frequently runs half marathons and 10ks together with is wife. Brandon also enjoys reading, playing piano, discussing philosophy, and playing chess. He is currently a Pgy5 neurosurgery resident at University of Florida with pursuing endovascular enfolded training and was awarded the Dempsey Cerebrovascular Research Fellowship.