Abstract
Thiazolidinediones (TZDs) are neuroprotective in rodent stroke models using intra-peritoneal, intra-venous and inter-ventricular routes of administration.We tested if oral pioglitazone at doses similar to those used by humans to treat diabetes reduces infarction volume following middle cerebral artery occlusion (MCAO) in the rat. Rats were fed DMSO or pioglitazone (0.65mg/kg equivalent to a 45mg dose in a 70kg man, 0.40mg/kg equivalent to a 30mg dose or 0.20mg/kg to a15mg dose) dissolved in DMSO daily for five days prior to 2 hour MCAO. Animals underwent serial functional analysis using the modified neurologic stroke scale (mNSS), the adhesive sticker test and the inclined plane, all of which test motor sensory function. Twenty one days later, MCAO rats were sacrificed and infarct volumes determined. We found significant reductions in the infarct volume using the 0.65 and 0.40mg/kg dose. Furthermore, these rats had improved performance on behavioural assays. The 0.20mg/kg dose did not significantly reduce infarction volume or improve behaviour.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Ginsberg M(2008) Neuroprotection for ischemic stroke: past, present and future. Neuropharm 55: 363-389.
Daynes RA, Jones DC (2002) Emerging roles of PPARs in inflammation and immunity. Nat Rev Immunol 2: 748-759.
Girnun GD, Domann FE, Moore SA et al. (2002) Identification of a functional peroxisome proliferator-activated receptor response element in the rat catalase promoter. Mol Endocrinol 16: 2793-801.
Shimazu T, Inoue I, ArakiNet al. (2005)Aperoxisome proliferator-activated receptor-g agonist reduces infarct size in transient but not in permanent ischemia. Stroke 36: 353-359.
Sundararajan S, Gamboa JL, Victor NA, et al. (2005) PPARg ligands reduce inflammation and infarction size in transient focal ischemia. Neurosci 130: 685-696.
Victor NA, Wanderi EW, Gamboa JL et al. (2006) Altered PPARgamma expression and activation after transient focal ischemia in rats. Eur J Neurosci 24: 1653-1663.
Allahtavokoli M, Shabanzadeh AP, Sadr SS et al. (2006) Rosiglitazone, a peroxisome proliferator-activated receptor-gamma ligand, reduces infarction volume and neurological deficits in an embolic model of stroke. Clin Exp Pharmacol Physiol 33: 1052-1058.
LinT-N,CheungW-M,Wu J-S et al. (2006) 15D-prostaglandin J2 protects brain fromischemiareperfusion injury. Arterioscler Thromb Vasc Biol 26: 481-487.
Lou Y, Yin W, Signore AP et al. (2006) Neuroprotection against focal ischemic brain injury by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone. J Neurochem 97: 435-448.
OuZ, Zhao X, LabicheL et al. (2006) Neuronal expression of peroxisome proliferator-activated receptor-gamma (PPARgamma) and 15D—prostaglandin J2-mediated protection after experimental cerebral ischemia in the rat. Brain Res 1096: 196-203.
Pereira MP, Hurtado O, Cardenas A et al. (2006) Rosiglitazone and 15D-deoxy-delta 12, 14- prostaglandin J2 cause potent neuroprotection after experimental stroke through noncompletely overlapping mechanisms. J Cereb Blood Flow Metab 26: 218-229.
Tureyen K, Kapadia R, Bowen KK et al (2007) Peroxisome proliferator-activated receptor-g agonists induce neuroprotection following transient focal ischemia in normotensive, normoglycemic as well as hypertensive and type-2 diabetic rodents. J Neurochem 101: 41-56.
Chen J, Sanberg P, Li Y (2001) Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats. Stroke 32: 2682-2688.
Zhang L, Chen J, Li Y (2000) Quantitative measurement of motor and somatosensory impairments after mild (30min) and severe (2h) transient middle cerebral artery occlusion in rats. J Neurol Sci 174: 141-146.
Yonemori F, Yamaguchi T, Yamada H (1998) Evaluation of motor deficit after chronic focal ischemia in rats. J Cereb Blood Flow Metab 18: 1099-1106.
Maeshiba Y, Yutaka Y, Yamashita K (1997) Disposition of the new antidiabetic agent pioglitazone in rats, dogs and monkeys. Arzneim-Forsch/Drug Res 47: 29-35. BookID 117032_ChapID 22_Proof# 1 - 13/02/2011
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC
About this paper
Cite this paper
Blankenship, D., Niemi, J., Hilow, E., Karl, M., Sundararajan, S. (2011). Oral Pioglitazone Reduces Infarction Volume and Improves Neurologic Function Following MCAO in Rats. In: LaManna, J., Puchowicz, M., Xu, K., Harrison, D., Bruley, D. (eds) Oxygen Transport to Tissue XXXII. Advances in Experimental Medicine and Biology, vol 701. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-7756-4_22
Download citation
DOI: https://doi.org/10.1007/978-1-4419-7756-4_22
Published:
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4419-7755-7
Online ISBN: 978-1-4419-7756-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)