{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:04:30Z","timestamp":1790553870582,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T00:00:00Z","timestamp":1623369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NINDS","award":["R01NS080844"],"award-info":[{"award-number":["R01NS080844"]}]},{"name":"MSCERP","award":["P20GM121334"],"award-info":[{"award-number":["P20GM121334"]}]},{"DOI":"10.13039\/501100003711","name":"MOST","doi-asserted-by":"publisher","award":["103-2320-B-030-MY3"],"award-info":[{"award-number":["103-2320-B-030-MY3"]}],"id":[{"id":"10.13039\/501100003711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shin Kong WHS Memorial Hospital, Taiwan","award":["106-SKH-FJU-06"],"award-info":[{"award-number":["106-SKH-FJU-06"]}]},{"name":"Shin Kong WHS Memorial Hospital, Taiwan","award":["100-SKH-FJU-04"],"award-info":[{"award-number":["100-SKH-FJU-04"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Previous studies have demonstrated that pioglitazone, a peroxisome proliferator-activated receptor gamma (PPAR\u03b3) agonist, inhibits ischemia-induced brain injury. The present study was conducted to examine whether pioglitazone can reduce impairment of behavioral deficits mediated by inflammatory-induced brain white matter injury in neonatal rats. Intraperitoneal (i.p.) injection of lipopolysaccharide (LPS, 2 mg\/kg) was administered to Sprague\u2013Dawley rat pups on postnatal day 5 (P5), and i.p. administration of pioglitazone (20 mg\/kg) or vehicle was performed 5 min after LPS injection. Sensorimotor behavioral tests were performed 24 h after LPS exposure, and changes in biochemistry of the brain was examined after these tests. The results show that systemic LPS exposure resulted in impaired sensorimotor behavioral performance, reduction of oligodendrocytes and mitochondrial activity, and increases in lipid peroxidation and brain inflammation, as indicated by the increment of interleukin-1\u03b2 (IL-1\u03b2) levels and number of activated microglia in the neonatal rat brain. Pioglitazone treatment significantly improved LPS-induced neurobehavioral and physiological disturbances including the loss of body weight, hypothermia, righting reflex, wire-hanging maneuver, negative geotaxis, and hind-limb suspension in neonatal rats. The neuroprotective effect of pioglitazone against the loss of oligodendrocytes and mitochondrial activity was associated with attenuation of LPS-induced increment of thiobarbituric acid reactive substances (TBARS) content, IL-1\u03b2 levels and number of activated microglia in neonatal rats. Our results show that pioglitazone prevents neurobehavioral disturbances induced by systemic LPS exposure in neonatal rats, and its neuroprotective effects are associated with its impact on microglial activation, IL-1\u03b2 induction, lipid peroxidation, oligodendrocyte production and mitochondrial activity.<\/jats:p>","DOI":"10.3390\/ijms22126306","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T12:44:37Z","timestamp":1623415477000},"page":"6306","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Pioglitazone Ameliorates Lipopolysaccharide-Induced Behavioral Impairment, Brain Inflammation, White Matter Injury and Mitochondrial Dysfunction in Neonatal Rats"],"prefix":"10.3390","volume":"22","author":[{"given":"Jiann-Horng","family":"Yeh","sequence":"first","affiliation":[{"name":"Department of Neurobiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan"},{"name":"School of Medicine, Fu Jen Catholic University, Xinzhuang Dist., New Taipei City 24205, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Ching","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Fu Jen Catholic University, Xinzhuang Dist., New Taipei City 24205, Taiwan"},{"name":"Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asuka","family":"Kaizaki","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics, Division of Toxicology, School of Pharmacy, Showa University, Shingawa-ku, Tokyo 142-8555, Japan"},{"name":"Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan W.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Chi","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Medicine, Fu Jen Catholic University, Xinzhuang Dist., New Taipei City 24205, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle A.","family":"Tucci","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma B.","family":"Ojeda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lir-Wan","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu-Tai","family":"Tien","sequence":"additional","affiliation":[{"name":"School of Medicine, Fu Jen Catholic University, Xinzhuang Dist., New Taipei City 24205, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1159\/000346682","article-title":"Ischemia-induced neuroinflammation is associated with disrupted development of oligodendrocyte progenitors in a model of periventricular leukomalacia","volume":"35","author":"Falahati","year":"2013","journal-title":"Dev. 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