Accession Number : ADA530730

Title :   Novel Nitroxide Resuscitation Strategies in Experimental Traumatic Brain Injury

Descriptive Note : Final rept. 13 Feb 2006-12 Feb 2010

Corporate Author : PITTSBURGH UNIV PA

Personal Author(s) : Kochanek, Patrick M

Full Text :

Report Date : Mar 2010

Pagination or Media Count : 78

Abstract : In this funding period, we developed a new model of combined experimental traumatic brain injury (TBI) plus hemorrhagic shock to study the effect of resuscitation with novel polynitroxylated colloids or hemoglobins in a series of 18 experimental studies carried out over 4 years. The most important finding was that a novel polynitroxylated, pegylated bovine cell-free hemoglobin (PNPH, a 4% solution in saline) served as a small volume resuscitation fluid that improved brain tissue oxygen levels and was neuroprotective. This neuroprotection was not seen with conventional resuscitation solutions such as lactated Ringers, Hextend, or hypertonic saline. A polynitroxylated albumin solution was also not as effective as PNPH. In addition, using a series of in vitro models of primary rat hippocampal neuronal culture, including glutamate/glycine toxicity and neuronal stretch injury, PNPH was shown to be uniquely neuroprotective in vitro-while native bovine hemoglobin was (as expected) neurotoxic. We believe that these findings are important and suggest that covalent modification of hemoglobin with the combination of antioxidant nitroxides and polyethylene glycol produces a potential paradigm shift in the development of new hemoglobins as resuscitation fluids. PNPH deserves additional study to move it to IND for TBI resuscitation.


Subject Categories : Biochemistry
      Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE