| Pioglitazone attenuates mitochondrial dysfunction, cognitive impairment, cortical tissue loss, and inflammation following traumatic brain injury. | |
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MedLine Citation:
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PMID: 20965168 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Following traumatic brain injury (TBI) there is significant neuropathology which includes mitochondrial dysfunction, loss of cortical gray matter, microglial activation, and cognitive impairment. Previous evidence has shown that activation of the peroxisome proliferator-activated receptors (PPARs) provide neuroprotection following traumatic brain and spinal injuries. In the current study we hypothesized that treatment with the PPAR ligand Pioglitazone would promote neuroprotection following a rat controlled cortical impact model of TBI. Animals received a unilateral 1.5mm controlled cortical impact followed by administration of Pioglitazone at 10mg/kg beginning 15min after the injury and subsequently every 24h for 5days. Beginning 1day after the injury there was significant impairment in mitochondrial bioenergetic function which was attenuated by treatments with Pioglitazone at 15min and 24h (p<0.05). In an additional set of animals, cognitive function was assessed using the Morris Water Maze (MWM) and it was observed that over the course of 4days of testing the injury produced a significant increase in both latency (p<0.05) and distance (p<0.05) to the platform. Animals treated with Pioglitazone performed similarly to sham animals and did not exhibit any impairment in MWM performance. Sixteen days after the injury tissue sections through the lesion site were quantified to determine the size of the cortical lesion. Vehicle-treated animals had an average lesion size of 5.09±0.73mm(3) and treatment with Pioglitazone significantly reduced the lesion size by 55% to 2.27±0.27mm(3) (p<0.01). Co-administration of the antagonist T0070907 with Pioglitazone blocked the protective effect seen with administration of Pioglitazone by itself. Following the injury there was a significant increase in the number of activated microglia in the area of the cortex adjacent to the site of the lesion (p<0.05). Treatment with Pioglitazone prevented the increase in the number of activated microglia and no difference was observed between sham and Pioglitazone-treated animals. From these studies we conclude that following TBI Pioglitazone is capable ameliorating multiple aspects of neuropathology. These studies provide further support for the use of PPAR ligands, specifically Pioglitazone, for neuroprotection. |
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Authors:
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Andrew Sauerbeck; Jianxin Gao; Ryan Readnower; Mei Liu; James R Pauly; Guoying Bing; Patrick G Sullivan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-10-20 |
Journal Detail:
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Title: Experimental neurology Volume: 227 ISSN: 1090-2430 ISO Abbreviation: Exp. Neurol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-10 Completed Date: 2011-02-04 Revised Date: 2012-04-30 |
Medline Journal Info:
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Nlm Unique ID: 0370712 Medline TA: Exp Neurol Country: United States |
Other Details:
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Languages: eng Pagination: 128-35 Citation Subset: IM |
Copyright Information:
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2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40536, USA. Adsaue2@uky.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Antigens, CD11b / metabolism Brain Injuries / complications, pathology Cerebral Cortex / drug effects*, pathology Cognition Disorders / drug therapy*, etiology, pathology Disease Models, Animal Encephalitis / drug therapy*, etiology Hypoglycemic Agents / therapeutic use* Male Maze Learning / drug effects Mitochondria / drug effects Mitochondrial Diseases / drug therapy*, etiology PPAR gamma / metabolism Rats Rats, Sprague-Dawley Thiazolidinediones / therapeutic use* Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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5 T 32 AG000242/AG/NIA NIH HHS; P30 NS051220/NS/NINDS NIH HHS; P30 NS051220-01/NS/NINDS NIH HHS; R01 NS048191-01/NS/NINDS NIH HHS; R01 NS062993/NS/NINDS NIH HHS; R01 NS062993/NS/NINDS NIH HHS; R01 NS062993-01A2/NS/NINDS NIH HHS; R01 NS48191/NS/NINDS NIH HHS; T32 AG000242-09/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD11b; 0/Hypoglycemic Agents; 0/PPAR gamma; 0/Thiazolidinediones; 111025-46-8/pioglitazone |
| Comments/Corrections | |
Comment In:
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Exp Neurol. 2011 Jun;229(2):195-7
[PMID:
21316363
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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