title: Loss of PPARα perpetuates sex differences in stroke reflected by peripheral immune mechanisms.
abstract: Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor transcription factor that plays a role in immune regulation. Because of its expression in cerebral tissue and immune cells, PPARα has been examined as an important regulator in immune-based neurological diseases. Many studies have indicated that pre-treatment of animals with PPARα agonists induces protection against stroke. However, our previous reports indicate that protection is only in males, not females, and can be attributed to different PPARα expression between the sexes. In the current study, we examine how loss of PPARα affects male and female mice in experimental stroke. Male and female PPARα knockout mice were subject to middle cerebral artery occlusion (MCAO) or sham surgery, and the ischemic (local) or spleen specific (peripheral) immune response was examined 96 h after reperfusion. We found that loss of PPARα perpetuated sex differences in stroke, and this was driven by the peripheral, not local, immune response. Specifically we observed an increase in peripheral pro-inflammatory and adhesion molecule gene expression in PPARα KO males after MCAO compared to females. Our data supports previous evidence that PPARα plays an important role in sex differences in the immune response to disease, including stroke.
authors: Neuroimmunology Research, R&D-31, Veterans Affairs Medical Center, 3710 SW US Veterans Hospital Rd., Portland, OR, 97239, USA.|Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
authors: Abby L
authors: AL
authors: Dotson
authors: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA.
authors: Jianming
authors: J
authors: Wang
authors: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA.
authors: Jian
authors: J
authors: Liang
authors: Neuroimmunology Research, R&D-31, Veterans Affairs Medical Center, 3710 SW US Veterans Hospital Rd., Portland, OR, 97239, USA.|Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
authors: Ha
authors: H
authors: Nguyen
authors: Neuroimmunology Research, R&D-31, Veterans Affairs Medical Center, 3710 SW US Veterans Hospital Rd., Portland, OR, 97239, USA.|Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
authors: Dustin
authors: D
authors: Manning
authors: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA.
authors: Julie A
authors: JA
authors: Saugstad
authors: Neuroimmunology Research, R&D-31, Veterans Affairs Medical Center, 3710 SW US Veterans Hospital Rd., Portland, OR, 97239, USA. offnerva@ohsu.edu.|Department of Neurology, Oregon Health & Science University, Portland, OR, USA. offnerva@ohsu.edu.|Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA. offnerva@ohsu.edu.
authors: Halina
authors: H
authors: Offner
mesh_terms: D000818:Animals; D005260:Female; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D012727:Sex Characteristics; D013154:Spleen / Q000378:metabolism; D020521:Stroke / Q000378:metabolism*
chemical_list: D047493:PPAR alpha
keywords: Experimental stroke; Inflammation; Knock out; PPARα; Sex difference