Neuronal cell death in ischemia and trauma.
Dr. Graham is the Connolly Family Chair in the Stroke Institute
Dr. Graham’s research focuses on the mechanisms by which neurons die after stroke and brain trauma. New insights into the mechanisms by which cyclooxygenase 2 (COX2), the enzyme that is the target of drugs such as Vioxx, injures neurons after anoxia in vitro were obtained during the 2004-5 academic year. These results suggest that prostaglandins, not the peroxidase activity of the enzyme itself, are responsible for COX2’s toxic effect on neurons. Other ongoing research projects address the role of the Fas cell death receptor in stroke and brain trauma. An adenovirus associated viral vector that expresses cFLIP-L, an endogenous inhibitor of Fas-induced cell death, has been constructed and is being tested in models of ischemia in vitro. We have found that mice with mutations in the Fas ligand have fewer apoptotic neurons 24 h after traumatic brain injury, consistent with a role of Fas in neuronal death after TBI.