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View Printer Friendly           Home | Research | Fellowship and Award Opportunities | Jason S. Weinstein, MD

2008 Research Fellow Jason S. Weinstein, MD Oregon Health and Sciences University Optimization of N-acetylcysteine (NAC) Administration for Neuroprotection in an Experimental Rat CNS Injury Model and Investigations into the Pathophysiology of Posttraumatic Hydrocephalus (PTH). Traumatic brain injury (TBI) remains a major source of morbidity and mortality with 1.5 million sustaining TBI each year; of these, 80-90,000 experience long-term disability (CDC 2001). There are currently no effective pharmacological agents used in clinical practice that reduce secondary brain injury. Additionally, hydrocephalus occurs in 20% of these patients and is associated with poor outcome (Marmarou 1996). The mechanism for posttraumatic hydrocephalus formation is incompletely understood, but likely involves fibrosis of the pathways of cerebrospinal fluid (CSF) absorption: cervical lymphatics and arachnoid granulations. Fibrosis following TBI may be due to induction of connective tissue growth factor (CTGF) which is, in turn, regulated by reactive oxygen species (ROS). One of the physiological defense mechanisms against oxidative stress involves removal of free radicals by the tripeptide glutathione (GSH), formed by three amino acids: glutamate, glycine, and cysteine. N-acetylcysteine (NAC), a thiol containing molecule, has both direct anti-oxidant activity and serves as a precursor for GSH biosynthesis. The following experimental design is intended to optimize administration of NAC for neuroprotection in an experimental rat TBI model, provide novel insight into the mechanism and prevention of posttraumatic hydrocephalus, and, if successful, will lead directly to clinical trials of NAC in human TBI.