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Peroxisome proliferator-activated receptorsgamma (PPARgamma) differently modulate the interleukin-6 expression in the peri-infarct cortical tissue in the acute and delayed phases of cerebral ischaemia.
Eur J Neurosci. 2008 Nov; 28(9):1786-94.EJ

Abstract

Interleukin-6 (IL-6) exerts neuroprotective effects after cerebral ischaemia but can also exacerbate inflammation and induce neuronal death. The current study investigates the role of cerebral peroxisome proliferator-activated receptor(s) gamma (PPARgamma) in the regulation of IL-6 expression in the peri-infarct cortical tissue in rats exposed to focal cerebral ischaemia. Pioglitazone, a high-affinity PPARgamma ligand, was infused intracerebroventricularly (i.c.v.) via osmotic minipumps over a 5-day period before, during and 24 h or 48 h after middle cerebral artery occlusion (MCAO) for 90 min followed by reperfusion. The expression of PPARgamma and IL-6 in cortical tissue adjacent to the ischaemic core was studied 24 h and 48 h after MCAO. Pioglitazone augmented the ischaemia-induced upregulation of PPARgamma at both time points. Cerebral ischaemia substantially increased IL-6 expression in the peri-infarct cortical tissue. Twenty-four hours after MCAO, the majority of microglial cells/macrophages showed an intense IL-6 immunoreactivity. IL-6 was also localized in neurons, but the distribution of neurons positively stained for IL-6 at the border of the infarct was very heterogeneous. Pioglitazone effectively decreased the number of IL-6-immunoreactive cells and IL-6 protein levels at 24 h but not at 48 h after MCAO. Pioglitazone treatment reduced the infarct size and improved neurological functions. The present study demonstrates that cerebral PPARgamma suppresses the expression of IL-6 in ischaemic brain tissue during the initial phase of ischaemic stroke, in which the overproduction of IL-6 may aggravate neuronal damage, but not at later time points, when IL-6 promotes neuroprotection and inhibits neuronal death.

Authors+Show Affiliations

Institute of Pharmacology, University Hospital of Schleswig-Holstein, Kiel, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18973594

Citation

Patzer, Andreas, et al. "Peroxisome Proliferator-activated Receptorsgamma (PPARgamma) Differently Modulate the Interleukin-6 Expression in the Peri-infarct Cortical Tissue in the Acute and Delayed Phases of Cerebral Ischaemia." The European Journal of Neuroscience, vol. 28, no. 9, 2008, pp. 1786-94.
Patzer A, Zhao Y, Stöck I, et al. Peroxisome proliferator-activated receptorsgamma (PPARgamma) differently modulate the interleukin-6 expression in the peri-infarct cortical tissue in the acute and delayed phases of cerebral ischaemia. Eur J Neurosci. 2008;28(9):1786-94.
Patzer, A., Zhao, Y., Stöck, I., Gohlke, P., Herdegen, T., & Culman, J. (2008). Peroxisome proliferator-activated receptorsgamma (PPARgamma) differently modulate the interleukin-6 expression in the peri-infarct cortical tissue in the acute and delayed phases of cerebral ischaemia. The European Journal of Neuroscience, 28(9), 1786-94. https://doi.org/10.1111/j.1460-9568.2008.06478.x
Patzer A, et al. Peroxisome Proliferator-activated Receptorsgamma (PPARgamma) Differently Modulate the Interleukin-6 Expression in the Peri-infarct Cortical Tissue in the Acute and Delayed Phases of Cerebral Ischaemia. Eur J Neurosci. 2008;28(9):1786-94. PubMed PMID: 18973594.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Peroxisome proliferator-activated receptorsgamma (PPARgamma) differently modulate the interleukin-6 expression in the peri-infarct cortical tissue in the acute and delayed phases of cerebral ischaemia. AU - Patzer,Andreas, AU - Zhao,Yi, AU - Stöck,Ivonne, AU - Gohlke,Peter, AU - Herdegen,Thomas, AU - Culman,Juraj, PY - 2008/11/1/pubmed PY - 2009/1/22/medline PY - 2008/11/1/entrez SP - 1786 EP - 94 JF - The European journal of neuroscience JO - Eur J Neurosci VL - 28 IS - 9 N2 - Interleukin-6 (IL-6) exerts neuroprotective effects after cerebral ischaemia but can also exacerbate inflammation and induce neuronal death. The current study investigates the role of cerebral peroxisome proliferator-activated receptor(s) gamma (PPARgamma) in the regulation of IL-6 expression in the peri-infarct cortical tissue in rats exposed to focal cerebral ischaemia. Pioglitazone, a high-affinity PPARgamma ligand, was infused intracerebroventricularly (i.c.v.) via osmotic minipumps over a 5-day period before, during and 24 h or 48 h after middle cerebral artery occlusion (MCAO) for 90 min followed by reperfusion. The expression of PPARgamma and IL-6 in cortical tissue adjacent to the ischaemic core was studied 24 h and 48 h after MCAO. Pioglitazone augmented the ischaemia-induced upregulation of PPARgamma at both time points. Cerebral ischaemia substantially increased IL-6 expression in the peri-infarct cortical tissue. Twenty-four hours after MCAO, the majority of microglial cells/macrophages showed an intense IL-6 immunoreactivity. IL-6 was also localized in neurons, but the distribution of neurons positively stained for IL-6 at the border of the infarct was very heterogeneous. Pioglitazone effectively decreased the number of IL-6-immunoreactive cells and IL-6 protein levels at 24 h but not at 48 h after MCAO. Pioglitazone treatment reduced the infarct size and improved neurological functions. The present study demonstrates that cerebral PPARgamma suppresses the expression of IL-6 in ischaemic brain tissue during the initial phase of ischaemic stroke, in which the overproduction of IL-6 may aggravate neuronal damage, but not at later time points, when IL-6 promotes neuroprotection and inhibits neuronal death. SN - 1460-9568 UR - https://www.unboundmedicine.com/medline/citation/18973594/Peroxisome_proliferator_activated_receptorsgamma__PPARgamma__differently_modulate_the_interleukin_6_expression_in_the_peri_infarct_cortical_tissue_in_the_acute_and_delayed_phases_of_cerebral_ischaemia_ L2 - https://doi.org/10.1111/j.1460-9568.2008.06478.x DB - PRIME DP - Unbound Medicine ER -