Accession Number:

ADA614244

Title:

Neuroinflammatory Pathobiology in Gulf War Illness: Characterization with an Animal Model

Descriptive Note:

Final rept. 1 Aug 2009 31 May 2014

Corporate Author:

ILLINOIS UNIV AT PEORIA COLL OF MEDICINE

Personal Author(s):

Report Date:

2014-06-01

Pagination or Media Count:

33.0

Abstract:

Chemical exposures are thought to precipitate the chronic symptoms associated with GWI. Chief among these are nerve agents encountered during deployment, treatment with a reversible cholinesterase inhibitor, and the use of pesticides. Cholinesterase inhibition has been proposed as a basis for the symptoms of GWI, and sarin is known to result in neuroinflammation. Physiologic stress experienced in theater also has been proposed as a contributor to GWI, and our results confirm that prior exposure to corticosterone CORT can enhance neuroinflammation. In this work we demonstrate that the sarin surrogate diisopropylphosphorofluoridate DFP results in neuroinflammation in mouse brain, an effect on multiple proinflammatory cytokines that is markedly enhanced by prior exposure to CORT and suggests the pathophysiological basis of GWI. GWI is characteristic of the sickness behavior typical of an inflammatory response to infection or injury, and a protracted condition is consistent with symptoms observed in ill veterans. We also have demonstrated that episodic exposure to CORT over an 180-day post-DFP period reveals a markedly enhanced priming effect that persists indefinitely. Finally, we found that an anti-inflammatory response, suggesting the use of non-steroidal anti-inflammatory drugs in the chronic treatment of GWI.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE