CORRELATION OF MATRIX METALLOPROTEINASE AND FUNCTIONAL OUTCOME FOLLOWING TRAUMA

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Traumatic brain injury (TBI) increases Matrix Metalloproteinase (MMP)-2 and -9 and the increase in these levels correlate with the Glasgow Outcome Score (GOS) and Rancho Los Amigos Cognitive Functioning Scale (LCFS). Specific aims: Patients with severe brain injury undergo monitoring of the cerebrospinal fluid (CSF) pressure by the insertion of a catheter into the cerebral ventricles. The pressure is monitored and the CSF is withdrawn when the pressure is elevated. CSF reflects the changes in the brain interstitial fluid and measurements of substrates in the CSF provide an indication of the biochemical changes that are occurring in the brain. An increase in CSF proteins, including MMPs, occurs in several neurological diseases. We plan to measure the levels of MMPs in the CSF by a sensitive zymographic method. Aim 1: To carefully select an appropriate TBI cohort for MMP level analysis in plasma and CSF and to obtain samples of CSF from brain injured patients at the time of admission, 24 and 72 hours after the injury, and at the time of the removal of the ventriculostomy. Aim 2: To establish the time course of MMP-2 and -9 expression and activation in CSF and plasma. Aim 3: To determine the correlation of GOS and LCFS to MMP levels.