Oral pioglitazone reduces infarction volume and improves neurologic function following MCAO in rats

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 (0.65 mg/kg equivalent to a 45 mg dose in a 70 kg man, 0.40 mg/kg equivalent to a 30 mg dose or 0.20mg/kg to a 15 mg 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 0.40 mg/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.