Document Detail

Effects of chronic overexpression of interleukin-1 receptor antagonist in a model of permanent focal cerebral ischemia in mouse.
MedLine Citation:
PMID:  15138779     Owner:  NLM     Status:  MEDLINE    
Interleukin-1 receptor antagonist (IL-1ra) has been shown previously to have neuroprotective effects in animal models of stroke. The effects of chronic overexpression of human soluble IL-1ra (hsIL-1ra) were studied in a mouse model of permanent focal cerebral ischemia. A transgenic mouse strain (Tg hsIL-1ra+/-) has been developed using the promoter for glial fibrillary acidic protein (GFAP) to limit the overexpression to the CNS. Analysis of the neurological scores, infarct volume and edema formation revealed no differences between Tg hsIL-1ra+/- and wild-type (WT) mice. The cerebral ischemia resulted in pronounced astrocyte proliferation and microglial activation, as well as induction of inflammatory markers in both Tg hsIL-1ra+/- and WT mice, with no major differences between the two genotypes. Interestingly, hsIL-1ra expression in astrocytes was reduced in infarcted areas as compared to non-ischemic regions and sham-operated controls. In conclusion, transgenic overexpression of hsIL1-ra was not neuroprotective in this cerebral ischemia model, possibly due to insufficient levels for protection against the extensive lesion, or an up-regulation of compensatory inflammatory signals due to the lifetime blockade of IL-1 receptors.
Mircea Oprica; Anne-Marie Van Dam; Johan Lundkvist; Kerstin Iverfeldt; Bengt Winblad; Tamas Bartfai; Marianne Schultzberg
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-05-08
Journal Detail:
Title:  Acta neuropathologica     Volume:  108     ISSN:  0001-6322     ISO Abbreviation:  Acta Neuropathol.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-06-09     Completed Date:  2004-10-15     Revised Date:  2007-11-09    
Medline Journal Info:
Nlm Unique ID:  0412041     Medline TA:  Acta Neuropathol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  69-80     Citation Subset:  IM    
Neurotec Department, Division of Experimental Geriatrics, Karolinska Institutet, Novum, Karolinska University Hospital Huddinge, 141 86, Stockholm, Sweden.
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MeSH Terms
Brain Edema / etiology,  genetics,  metabolism,  pathology
Brain Infarction / etiology,  genetics,  metabolism,  pathology
Brain Ischemia / etiology,  genetics,  metabolism*
Caspase 1 / metabolism
Disease Models, Animal
Fluorescent Antibody Technique / methods
Gene Expression Regulation / genetics*
Glial Fibrillary Acidic Protein / genetics,  metabolism
Infarction, Middle Cerebral Artery / complications,  drug therapy,  genetics
Interleukin 1 Receptor Antagonist Protein
Interleukin-1 / metabolism
Mice, Inbred C57BL
Mice, Transgenic
Neuroglia / metabolism*
Neurologic Examination
Regional Blood Flow / physiology
Sialoglycoproteins / metabolism*
Reg. No./Substance:
0/Glial Fibrillary Acidic Protein; 0/IL1RN protein, human; 0/Il1rn protein, mouse; 0/Interleukin 1 Receptor Antagonist Protein; 0/Interleukin-1; 0/Sialoglycoproteins; EC 1

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