Peroxisome proliferator-activated receptor γ promotes neuroprotection by modulating cyclic D1 expression after focal cerebral ischemia
- 1 July 2010
- journal article
- Published by Canadian Science Publishing in Canadian Journal of Physiology and Pharmacology
- Vol. 88 (7), 716-723
- https://doi.org/10.1139/y10-058
Abstract
Peroxisome proliferator-activated receptor γ (PPARγ) has been shown to protect against stroke and improve neurological outcome after cerebral ischemia. This study investigated whether activation of cerebral PPARγ improves recovery from focal cerebral ischemia by reducing expression of cyclin D1, which is associated with programmed neuron death. Focal cerebral ischemia was induced by 90 min of middle cerebral artery occlusion (MCAO), followed by reperfusion. Intracerebroventricular (i.c.v.) infusion of the PPARγ agonist ciglitazone, beginning 5 days before and continuing through 1 day after MCAO, reduced infarct size and cyclin D1 expression in the peri-infarct cortical region. Furthermore, primary cortical neurons treated with ciglitazone showed suppressed expression of cyclin D1 in response to hypoxia–reoxygenation. This protective effect was reversed after cotreatment with the selective PPAR-γ antagonist GW 9662 (2-chloro-5-nitrobenzanilide), clearly demonstrating the involvement of a PPARγ-dependent mechanism. Our data provide evidence that activation of neuronal PPARγ makes a substantial contribution to neuroprotection by preventing cyclin D1 up-regulation in vitro and in vivo.Keywords
This publication has 33 references indexed in Scilit:
- Review: PPARs as new therapeutic targets for the treatment of cerebral ischemia/reperfusion injuryTherapeutic Advances in Cardiovascular Disease, 2008
- Hormone regulation of microglial cell activation: relevance to multiple sclerosisBrain Research Reviews, 2005
- Expression of peroxisome proliferator-activated receptors (PPARs) and retinoic acid receptors (RXRs) in rat cortical neuronsNeuroscience, 2005
- Cyclooxygenase-2 activity contributes to neuronal expression of cyclin D1 after anoxia/ischemia in vitro and in vivoMolecular Brain Research, 2004
- Pioglitazone Prevents Hypertension and Reduces Oxidative Stress in Diet-Induced ObesityHypertension, 2004
- Peroxisome Proliferator-Activated Receptor-γ Agonist 15-Deoxy-Δ12,1412,14-Prostaglandin J2 Ameliorates Experimental Autoimmune EncephalomyelitisThe Journal of Immunology, 2002
- PPAR-γ dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammationNature Medicine, 2001
- Role of the peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) and its natural ligand 15‐deoxy‐Δ12,14‐prostaglandin J2 in the regulation of microglial functionsEuropean Journal of Neuroscience, 2000
- Blockade of Central Angiotensin AT 1 Receptors Improves Neurological Outcome and Reduces Expression of AP-1 Transcription Factors After Focal Brain Ischemia in RatsStroke, 1999
- Serum‐free B27/neurobasal medium supports differentiated growth of neurons from the striatum, substantia nigra, septum, cerebral cortex, cerebellum, and dentate gyrusJournal of Neuroscience Research, 1995