Tags

Type your tag names separated by a space and hit enter

Pioglitazone Attenuates Neuroinflammation and Promotes Dopaminergic Neuronal Survival in the Nigrostriatal System of Rats after Diffuse Brain Injury.
J Neurotrauma. 2017 01 15; 34(2):414-422.JN

Abstract

Increasing evidence suggests that traumatic brain injury (TBI) may raise the risk of developing late-onset Parkinson's disease (PD). Recently, the peroxisome proliferation-activated receptor gamma (PPARγ) agonist pioglitazone has been demonstrated to be neuroprotective in animal models of neurodegeneration. The present study investigates the vulnerability of the nigrostriatal system after TBI, and intervention with pioglitazone treatment. Adult male Sprague-Dawley rats were subjected to sham or moderate midline fluid percussion brain injury (mFPI), followed by an intraperitoneal injection of 10 mg/kg pioglitazone or vehicle beginning 30 min after the injury and subsequently every 24 h for 5 days. Following injury, pro-inflammatory cytokines and chemokine were acutely increased in the striatum and substantia nigra within 6 h. Dopaminergic axonal damage and microglial activation were revealed using immunohistochemistry in the medial forebrain bundle at 1 day post-injury. Microglial activation identified by Iba1 and OX-6 immunostaining was persistently increased in the substantia nigra pars compacta 7 to 28 days post-injury. Further, brain injury induced significant dopaminergic neuronal loss, which was quantified by tyrosine hydroxylase immunostaining and retrograde fluorescent tracer fluorogold labeling in the nigra at 28 days. Loss of neurons was accompanied by increased extracellular dopamine (DA) turnover in the striatum, indicating enhanced dopaminergic activity in functional compensation after nigrostriatal damage. Strikingly, pioglitazone treatment greatly attenuated microglial activation and improved dopaminergic neuronal survival in the nigrostriatal system, which may promote locomotor recovery. These results suggest that interventions that attenuate secondary inflammation could be a feasible therapeutic treatment to improve outcome after TBI.

Authors+Show Affiliations

1 Department of Anatomy and Neurobiology, University of Kentucky College of Medicine , Lexington, Kentucky.2 Sanders-Brown Center on Aging, University of Kentucky College of Medicine , Lexington, Kentucky.1 Department of Anatomy and Neurobiology, University of Kentucky College of Medicine , Lexington, Kentucky.3 BARROW Neurological Institute at Phoenix Children's Hospital; Department of Child Health, University of Arizona College of Medicine, Phoenix, Arizona; Phoenix Veteran Affairs Healthcare System, Phoenix, Arizona; Interdisciplinary Graduate Program in Neuroscience, Arizona State University , Tempe, Arizona.1 Department of Anatomy and Neurobiology, University of Kentucky College of Medicine , Lexington, Kentucky.

Pub Type(s)

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

Language

eng

PubMed ID

27142118

Citation

Liu, Mei, et al. "Pioglitazone Attenuates Neuroinflammation and Promotes Dopaminergic Neuronal Survival in the Nigrostriatal System of Rats After Diffuse Brain Injury." Journal of Neurotrauma, vol. 34, no. 2, 2017, pp. 414-422.
Liu M, Bachstetter AD, Cass WA, et al. Pioglitazone Attenuates Neuroinflammation and Promotes Dopaminergic Neuronal Survival in the Nigrostriatal System of Rats after Diffuse Brain Injury. J Neurotrauma. 2017;34(2):414-422.
Liu, M., Bachstetter, A. D., Cass, W. A., Lifshitz, J., & Bing, G. (2017). Pioglitazone Attenuates Neuroinflammation and Promotes Dopaminergic Neuronal Survival in the Nigrostriatal System of Rats after Diffuse Brain Injury. Journal of Neurotrauma, 34(2), 414-422. https://doi.org/10.1089/neu.2015.4361
Liu M, et al. Pioglitazone Attenuates Neuroinflammation and Promotes Dopaminergic Neuronal Survival in the Nigrostriatal System of Rats After Diffuse Brain Injury. J Neurotrauma. 2017 01 15;34(2):414-422. PubMed PMID: 27142118.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pioglitazone Attenuates Neuroinflammation and Promotes Dopaminergic Neuronal Survival in the Nigrostriatal System of Rats after Diffuse Brain Injury. AU - Liu,Mei, AU - Bachstetter,Adam D, AU - Cass,Wayne A, AU - Lifshitz,Jonathan, AU - Bing,Guoying, Y1 - 2016/06/10/ PY - 2016/5/5/pubmed PY - 2018/1/13/medline PY - 2016/5/5/entrez KW - Parkinson's disease KW - brain injury KW - pioglitazone KW - substantia nigra SP - 414 EP - 422 JF - Journal of neurotrauma JO - J Neurotrauma VL - 34 IS - 2 N2 - Increasing evidence suggests that traumatic brain injury (TBI) may raise the risk of developing late-onset Parkinson's disease (PD). Recently, the peroxisome proliferation-activated receptor gamma (PPARγ) agonist pioglitazone has been demonstrated to be neuroprotective in animal models of neurodegeneration. The present study investigates the vulnerability of the nigrostriatal system after TBI, and intervention with pioglitazone treatment. Adult male Sprague-Dawley rats were subjected to sham or moderate midline fluid percussion brain injury (mFPI), followed by an intraperitoneal injection of 10 mg/kg pioglitazone or vehicle beginning 30 min after the injury and subsequently every 24 h for 5 days. Following injury, pro-inflammatory cytokines and chemokine were acutely increased in the striatum and substantia nigra within 6 h. Dopaminergic axonal damage and microglial activation were revealed using immunohistochemistry in the medial forebrain bundle at 1 day post-injury. Microglial activation identified by Iba1 and OX-6 immunostaining was persistently increased in the substantia nigra pars compacta 7 to 28 days post-injury. Further, brain injury induced significant dopaminergic neuronal loss, which was quantified by tyrosine hydroxylase immunostaining and retrograde fluorescent tracer fluorogold labeling in the nigra at 28 days. Loss of neurons was accompanied by increased extracellular dopamine (DA) turnover in the striatum, indicating enhanced dopaminergic activity in functional compensation after nigrostriatal damage. Strikingly, pioglitazone treatment greatly attenuated microglial activation and improved dopaminergic neuronal survival in the nigrostriatal system, which may promote locomotor recovery. These results suggest that interventions that attenuate secondary inflammation could be a feasible therapeutic treatment to improve outcome after TBI. SN - 1557-9042 UR - https://www.unboundmedicine.com/medline/citation/27142118/Pioglitazone_Attenuates_Neuroinflammation_and_Promotes_Dopaminergic_Neuronal_Survival_in_the_Nigrostriatal_System_of_Rats_after_Diffuse_Brain_Injury_ L2 - https://www.liebertpub.com/doi/10.1089/neu.2015.4361?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -