Effect Of PPARγ Agonist Pioglitazone Following Traumatic Brain Injury In Rats

Objective:Peroxisome proliferator-activated receptor gamma(PPARγ) is a ligand-activated transcription factor of nuclear hormone receptor superfamily. It plays an important role in glucose and lipid metabolism and cell proliferation and differentiation[1]. More recently, much of the research has focused on the anti-inflammatory effects of PPARγactivation by its agonists(ligands) on peripheral organs and the CNS after acute and chronic insults. Thiazolidinedione pioglitazone is a potent agonist of PPARγwhich was shown to induce neuroprotection in animal models of focal ischemia ,spinal cord injury and chronic CNS injuries like Parkinson's disease, Alzheimer's disease[2,3,4,5]. To explored the neuroprotection of PPARγagonist Pioglitazone following traumatic brain injury(TBI) in rats, We treated rats with Pioglitazone following traumatic brain injury. The neurological function, brain oedema, delayed neuronal death and apoptosis of neurocytes were observed. Meanwhile, the expression of ICAM-1 in brain tissue was evaluated. This study provided both rationale and experiment evidences for neuroprotection after TBI.Methods: The rat models were established by Feeney's free falling method.The male Sprague-Dawley rats were randomly divided into 3 groups: Pioglitazone treatment group(treated with Pioglitazone 10mg/kg gastric perfusion once at 30mins before TBI and 6h,12h,24h after TBI),control group(treated with the same volume saline gastric perfusion at the same times),sham operation group(treated with the same volume saline gastric perfusion at the same times).The neural deficit scores were tested at 6h,48h,5d after TBI respectively in order to evaluate neurological function. Brain water content(BWC) was estimated by dry-wet weighing method at 24h after TBI in order to evaluate brain oedema. HE, TUNEL and Nissl's staining were employed at 48h after TBI in order to observe injured cerebral cortex, delayed neuronal death and apoptosis of neurocytes. Immunohistochemistry of ICAM-1 was employed at 48h after TBI.Results:1.The TBI rat models were steady,repeatable and controllable. So the establishment of rat models were successful.2. The neural deficit scores in Pioglitazone treatment group were superior to control group at 48h,5d after TBI(P<0.05).3. The BWC was no significant difference between Pioglitazone treatment group and control group at 48h after TBI(P>0.05).4. The delayed dead and apoptotic neurocyte numbers in Pioglitazone treatment group were significantly lower than those in control group at 48h after TBI(P<0.05). 5. The expression of ICAM-1 in Pioglitazone treatment group was significantly lower than that in control group at 48h after TBI(P<0.05).Conclusion: The experiment has established the TBI model in rat successfully. The PPARγagonist Pioglitazone significantly reduced the numbers of the delayed dead and apoptotic neurocyte,and improve the prognosis of TBI. Meanwhile,it prevented the expression of ICAM-1 in brain tissue of rat after TBI,which maybe induce the anti-inflammatory of Pioglitazone.