Neuroinflammation and neuronal apoptosis in experimental closed head injury in mice

• Antragsteller: Professor Dr. Wolfgang Ertel, seit 3/2006
• Fachliche Zuordnung: Orthopädie, Unfallchirurgie, rekonstruktive Chirurgie
• Förderung: Förderung von 2003 bis 2011
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5408797

Traumatic brain injury (TBI) is the leading cause of death and long-term disability in young patients in industrialized nations. The exact mechanisms of neuronal cell death after TBI remain unclear. In particular, the role of FAS-induced neuronal apoptosis in the pathophysiology of TBI is controversial and remains to be elucidated. We plan to evaluate the effects of FAS-mediated neuropathology in vivo in a standardized experimental model of closed head injury in mice. The specific aims of the study are: 1) Evaluation of FAS-mediated detrimental effects in murine brains after injection of agonistic anti-FAS/CD95 antibodies in wild-type mice. The endpoints will be the analysis of blood-brain barrier function, cerebral edema and extent of neuronal apoptosis compared to control IgG-injected mice. 2) Analysis of changes in FAS-mediated neuropathology by exogenous caspase inhibition after experimental closed head injury in mice. The posttraumatic neuropathological sequelae (axonal injury, cytoskeletal damage, lipid peroxidation, altered intracranial energy metabolism). 3) Evaluation of posttraumatic neuropathology and neurological outcome after experimental brain injury in FAS-, FASL- and IL-18-deficient mice compared to wild-type littermates. In all study protocols, the regulation of intracerebral expression of inflammatory and pro-/anti-apoptotic genes will be assessed at defined time-points and compared to the according control groups. These experiments will further characterize the in vivo role of the FAS/FASL-system in contributing to secondary brain damage and neurological morbidity after brain injury.

• DFG-Verfahren: Schwerpunktprogramme
• Teilprojekt zu: SPP 1151: Immun- und Stoffwechselmodulation durch schweres Gewebstrauma
• Beteiligte Person: Dr. Oliver Schmidt
• Ehemaliger Antragsteller: Professor Dr. Philip F. Stahel, bis 3/2006