Role of post-traumatic hypoxia in the exacerbation of cerebral inflammatory response elicited by brain injury [ 2007 - 2009 ]

Research Grant

Researchers: A/Pr Cristina Morganti-Kossmann (Principal investigator) ,  Prof Thomas Kossmann

Brief description Traumatic brain injury is the major cause of death in the young population below the age of 40 years. Approximately 25% of patients that survive head injury remain with permanent neurological disabilities with considerable family, professional and economic costs. Extensive research has shown that not all brain damage occurs at the time of injury, but rather evolves over the hours and days following trauma. Secondary injury may result from various factors including hypoxia (insufficient oxygen) as a consequence of respiratory distress that occurs in about 50% of patients with severe head trauma. Hypoxia is known to significantly worsen the neurological impairment and potentially lead to death. Brain injury and hypoxia have the ability to separately trigger cerebral inflammation. A dual role has been attributed to inflammation: to promote tissue repair but also add further damage through the release of neurotoxic substances. We hypothesise that hypoxia occurring after traumatic brain injury enhances the inflammatory response in the brain and aggravate tissue damage as well as neurological dysfunction. This hypothesis will be tested on a rat model of brain injury whereby the animals will be exposed to moderate-severe hypoxia immediately after trauma. The production of multiple inflammatory mediators will be quantified in the brain tissue and also in cerebrospinal fluid. The concentration of these mediators will be compared with the levels of cellular injury proteins known to increase following injury to determine whether a correlation exists. In a clinical study on patients, we will measure the same inflammatory mediators and proteins in the cerebrospinal fluid and blood of individuals with severe head injury. The suitability of these factors for potential use as diagnostic-prognostic markers of either hypoxia or injury will be determined.

Funding Amount $AUD 397,535.49

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant