RGD Reference Report - The growth factor progranulin attenuates neuronal injury induced by cerebral ischemia-reperfusion through the suppression of neutrophil recruitment. - Rat Genome Database
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The growth factor progranulin attenuates neuronal injury induced by cerebral ischemia-reperfusion through the suppression of neutrophil recruitment.

Authors: Egashira, Y  Suzuki, Y  Azuma, Y  Takagi, T  Mishiro, K  Sugitani, S  Tsuruma, K  Shimazawa, M  Yoshimura, S  Kashimata, M  Iwama, T  Hara, H 
Citation: Egashira Y, etal., J Neuroinflammation. 2013 Aug 23;10:105. doi: 10.1186/1742-2094-10-105.
RGD ID: 10401661
Pubmed: (View Article at PubMed) PMID:23972823
DOI: Full-text: DOI:10.1186/1742-2094-10-105

BACKGROUND: To improve the clinical outcome of patients who suffered ischemic stroke, cerebral ischemia-reperfusion (I/R) injury is one of the major concerns that should be conquered. Inflammatory reactions are considered a major contributor to brain injury following cerebral ischemia, and I/R exacerbates these reactions. The aim of this study was to investigate the possible ameliorative effects of progranulin (PGRN) against I/R injury in mice. METHODS: In vivo I/R was induced in four-week-old male ddY mice by 2 h of MCAO (middle cerebral artery occlusion) followed by 22 h of reperfusion. We evaluate expression of PGRN in I/R brain, efficacy of recombinant-PGRN (r-PGRN) treatment and its therapeutic time-window on I/R injury. Two hours after MCAO, 1.0 ng of r-PRGN or PBS was administered via intracerebroventricular. We assess neutrophil infiltration, expression of tumor necrosis factor (TNF)-alpha, matrix metalloproteinase-9 (MMP-9) and phosphorylation of nuclear factor-kappaB (NF-kappaB) by immunofluorescense staining and Western blotting. We also investigate neutrophil chemotaxis and intercellular adhesion molecule-1 (ICAM-1) expression in vitro inflammation models using isolated neutrophils and endothelial cells. RESULTS: We found that expression of PGRN was decreased in the I/R mouse brain. r-PGRN treatment at 2 h after MCAO resulted in a reduction in the infarct volume and decreased brain swelling; this led to an improvement in neurological scores and to a reduction of mortality rate at 24 h and 7 d after MCAO, respectively. Immunohistochemistry, Western blotting, and gelatin zymography also confirmed that r-PGRN treatment suppressed neutrophil recruitment into the I/R brain, and this led to a reduction of NF-kappaB and MMP-9 activation. In the in vitro inflammation models, PGRN suppressed both the neutrophil chemotaxis and ICAM-1 expression caused by TNF-alpha in endothelial cells. CONCLUSIONS: PGRN exerted ameliorative effects against I/R-induced inflammation, and these effects may be due to the inhibition of neutrophil recruitment into the I/R brain.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Grn  (granulin precursor)

Genes (Mus musculus)
Grn  (granulin)

Genes (Homo sapiens)
GRN  (granulin precursor)


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