title: Spatiotemporal patterns of GFAP upregulation in rat brain following acute intoxication with diisopropylfluorophosphate (DFP).
abstract: We previously demonstrated that the organophosphate diisopropylfluorophosphate (DFP) induced region-specific delayed neuronal injury in rat brain. The goal of this study was to examine the spatiotemporal pattern of the astroglial response after acute intoxication of rats with DFP. Rats were euthanized at varying times between 1 h to 7 days after DFP administration (9mg/kg, i.p.). The distribution of activated astrocytes in different brain regions was determined by immunostaining for glial fibrillary acidic acid (GFAP). GFAP immunoreactivity increased in the hippocampus, and piriform/entorhinal cortex at 1 h, peaked between 4-8 h then decreased from 16 to 24 h. GFAP labeling in the amygdala gradually increased over the 24 h period. A large increase in GFAP labeling was seen at 3-7 days following DFP administration in the hippocampus, piriform/entorhinal cortex and dorsolateral thalamus. At 3 days post-DFP exposure, GFAP immunoreactivity was totally absent in central areas of the hippocampus, piriform/entorhinal cortex and dorsolateral thalamus that contained numerous FluoroJade B (FJB) labeled neurons. By 7 days, GFAP expression was highly upregulated in all areas of each brain region. The mRNA expression of GFAP in hippocampus slowly increased at 24 h following DFP administration then dramatically increased at 3 days. This study suggests that activation of glial cells may contribute to the early neuropathological changes and later neuronal repair/plasticity following acute DFP intoxication.
authors.affiliation: Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA, 30310, USA ; Institute of Infectious Disease, Xiangya Hospital, Central-South University, Changsha, China.
authors.forename: Cuimei
authors.initials: C
authors.lastname: Liu
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Li
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Lein
authors.forename: Byron D
authors.initials: BD
authors.lastname: Ford
keywords: DFP; GFAP; astrocytes; intoxication; organophosphate; seizure
references.citation: J Neuroimmunol. 1985 Jun;8(4-6):203-14
references.pmid: 2409105
references.citation: Ann Neurol. 2007 Jan;61(1):9-13
references.pmid: 17262854
references.citation: Toxicol Appl Pharmacol. 2011 Jun 15;253(3):261-9
references.pmid: 21513723
references.citation: Neurotoxicology. 2011 Mar;32(2):268-76
references.pmid: 21182866
references.citation: Neurosci Lett. 2003 Oct 9;349(3):147-50
references.pmid: 12951190
references.citation: J Comp Neurol. 2003 Jun 30;461(3):307-16
references.pmid: 12746870
references.citation: Toxicol Lett. 1991 Feb;55(2):131-47
references.pmid: 1998202
references.citation: Nature. 2009 Feb 5;457(7230):675-7
references.pmid: 19194443
references.citation: Ann Neurol. 2007 Jan;61(1):37-46
references.pmid: 17187377
references.citation: Acta Neurochir Suppl. 2004;89:87-92
references.pmid: 15335106
references.citation: Neuroreport. 1995 Dec 29;7(1):365-9
references.pmid: 8742489
references.citation: J Clin Neurosci. 2006 Nov;13(9):934-8
references.pmid: 17085299
references.citation: J Neuroinflammation. 2010 Jul 22;7:40
references.pmid: 20649973
references.citation: Neuroscience. 1991;45(3):541-9
references.pmid: 1775232
references.citation: Neuroscience. 1991;45(3):529-39
references.pmid: 1775231
references.citation: J Comp Neurol. 1997 Feb 24;378(4):482-92
references.pmid: 9034905
references.citation: Toxicology. 2005 Mar 30;208(3):319-34
references.pmid: 15695018
references.citation: Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6819-23
references.pmid: 1862105
references.citation: Toxicology. 2007 Sep 5;238(2-3):166-76
references.pmid: 17662515
references.citation: Chem Res Toxicol. 2009 Apr;22(4):633-8
references.pmid: 19281266
references.citation: J Cell Biol. 1999 May 3;145(3):503-14
references.pmid: 10225952
references.citation: Toxicol Appl Pharmacol. 2011 Sep 15;255(3):229-41
references.pmid: 21791221
references.citation: J Toxicol Environ Health A. 2008;71(2):119-30
references.pmid: 18080902
references.citation: Arch Environ Health. 2003 Aug;58(8):484-97
references.pmid: 15259428
references.citation: Neurosci Biobehav Rev. 1997 Sep;21(5):559-79
references.pmid: 9353792
references.citation: Neurochem Res. 2000 Jun;25(6):809-16
references.pmid: 10943999
references.citation: Neurotoxicology. 2006 Mar;27(2):277-83
references.pmid: 16406030
references.citation: Neurotoxicology. 2001 Jun;22(3):355-62
references.pmid: 11456336
references.citation: Glia. 1994 Jun;11(2):147-55
references.pmid: 7927644