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Clinical Trials with Dismutec™ (Pegorgotein; Polyethylene Glycol-Conjugated Superoxide Dismutase; PEG-SOD) in the Treatment of Severe Closed Head Injury

  • J. Paul Muizelaar
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 366)

Abstract

Although the suspicion for a role of oxygen radicals in disease and degeneration was raised a long time ago, the first publications relating free radicals with traumatic brain injury appeared only in 1981.1,2 Since then, however, a rapid development has taken place, culminating in a phase II human trial with a superoxide scavenger started in 19893 and several phase III clinical trials taking place at present. The initial laboratory experiments were concentrated on elucidating mechanisms for vascular damage after head injury. First, it was shown that in the early minutes after experimental fluid percussion injury in the cat, prostaglandin concentration in the brain increases, secondary to activation of the arachidonic acid pathway; this pathway leads to superoxide anion formation through the enzyme PGH synthase.1 Pretreatment with radical scavengers or with indomethacin, which inhibits cyclo-oxygenase and thus deprives the prostaglandin hydroperoxidase of substrate, protects the endothelium of the cerebral microcirculation from the effects of experimental brain injury.2 Subsequently, it was shown that immediately after the impact there is an increase in phospholipase C activity, which can release arachidonic acid in tissue, leading to oxygen radical formation.4 Further work showed that the radicals are produced not only in cerebral blood vessel walls but also in leukocytes and macrophages that accumulate in the brain between 3 and 24 hours after experimental injury.5 With the method used to identify the site of generation of the superoxide anion,6 only the vessel walls could be implicated in this process, but this is possibly because of insufficient penetration of the reagents into brain tissue.

Keywords

Traumatic Brain Injury Cerebral Blood Flow Head Injury Glasgow Coma Scale Glasgow Outcome Scale 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • J. Paul Muizelaar
    • 1
  1. 1.Division of NeurosurgeryMedical College of Virginia/Virginia Commonwealth UniversityRichmondUSA

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