Protective Effects of Pioglitazone Against Global Cerebral Ischemic-Reperfusion Injury in Gerbils
Despite of the huge socio-economic burden, stroke still represents an unmet therapeutic need. Researchers failed to reproduce preclinical efficacy in subsequent clinical development. To bridge this translation failure, the Stroke Therapy Academic Industry Round Table (STAIR) has suggested a rigorous...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2009-01-01
|
| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S134786131931254X |
| _version_ | 1818499432782495744 |
|---|---|
| author | Ravinder K. Kaundal Seethalakshmi Iyer Ashutosh Kumar Shyam S. Sharma |
| author_facet | Ravinder K. Kaundal Seethalakshmi Iyer Ashutosh Kumar Shyam S. Sharma |
| author_sort | Ravinder K. Kaundal |
| collection | DOAJ |
| description | Despite of the huge socio-economic burden, stroke still represents an unmet therapeutic need. Researchers failed to reproduce preclinical efficacy in subsequent clinical development. To bridge this translation failure, the Stroke Therapy Academic Industry Round Table (STAIR) has suggested a rigorous, robust, and detailed preclinical evaluation in at least 2 species and multiple cerebral ischemia models to avoid the clinical failure. Considering these recommendations, in the present study, we have investigated the effects of pioglitazone in global model cerebral ischemic-reperfusion (IR) injury in gerbils. Global cerebral IR injury, produced by bilateral carotid artery occlusion for 5 min, was characterized by neurological deficits, hyperlocomotion, and neurodegeneration in the hippocampal CA1 region. Global ischemia was also associated with oxidative stress and DNA fragmentation as evident from increased malondialdehyde (MDA) levels and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling)-positive cells. Global cerebral IR injury associated neurological damage was significantly attenuated by pioglitazone pretreatment as evident from reduction in neurological symptoms, hyperlocomotion, and CA1 hippocampal neuronal damage in IR-challenged gerbils. Pioglitazone pretreatment also attenuated the oxidative stress and DNA fragmentation after cerebral IR injury. Pioglitazone post-treatment has also significantly reduced the CA1 hippocampal neuronal damage and DNA fragmentation after cerebral IR injury in IR-challenged gerbils. This study demonstrates the neuroprotective activity of pioglitazone in global cerebral IR injury and its neuroprotective effects may be attributed to reduction in oxidative stress and DNA fragmentation. Keywords:: pioglitazone, bilateral carotid artery occlusion, TUNEL, peroxisome proliferator–activated receptor (PPAR), gerbil |
| first_indexed | 2024-12-10T20:29:25Z |
| format | Article |
| id | doaj.art-f62fc53f6e894a089ff8d4889667fa81 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-10T20:29:25Z |
| publishDate | 2009-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-f62fc53f6e894a089ff8d4889667fa812022-12-22T01:34:45ZengElsevierJournal of Pharmacological Sciences1347-86132009-01-011093361367Protective Effects of Pioglitazone Against Global Cerebral Ischemic-Reperfusion Injury in GerbilsRavinder K. Kaundal0Seethalakshmi Iyer1Ashutosh Kumar2Shyam S. Sharma3Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector- 67, S.A.S. Nagar, Punjab- 160062, IndiaMolecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector- 67, S.A.S. Nagar, Punjab- 160062, IndiaMolecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector- 67, S.A.S. Nagar, Punjab- 160062, IndiaMolecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector- 67, S.A.S. Nagar, Punjab- 160062, India; Corresponding author. sssharma@niper.ac.inDespite of the huge socio-economic burden, stroke still represents an unmet therapeutic need. Researchers failed to reproduce preclinical efficacy in subsequent clinical development. To bridge this translation failure, the Stroke Therapy Academic Industry Round Table (STAIR) has suggested a rigorous, robust, and detailed preclinical evaluation in at least 2 species and multiple cerebral ischemia models to avoid the clinical failure. Considering these recommendations, in the present study, we have investigated the effects of pioglitazone in global model cerebral ischemic-reperfusion (IR) injury in gerbils. Global cerebral IR injury, produced by bilateral carotid artery occlusion for 5 min, was characterized by neurological deficits, hyperlocomotion, and neurodegeneration in the hippocampal CA1 region. Global ischemia was also associated with oxidative stress and DNA fragmentation as evident from increased malondialdehyde (MDA) levels and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling)-positive cells. Global cerebral IR injury associated neurological damage was significantly attenuated by pioglitazone pretreatment as evident from reduction in neurological symptoms, hyperlocomotion, and CA1 hippocampal neuronal damage in IR-challenged gerbils. Pioglitazone pretreatment also attenuated the oxidative stress and DNA fragmentation after cerebral IR injury. Pioglitazone post-treatment has also significantly reduced the CA1 hippocampal neuronal damage and DNA fragmentation after cerebral IR injury in IR-challenged gerbils. This study demonstrates the neuroprotective activity of pioglitazone in global cerebral IR injury and its neuroprotective effects may be attributed to reduction in oxidative stress and DNA fragmentation. Keywords:: pioglitazone, bilateral carotid artery occlusion, TUNEL, peroxisome proliferator–activated receptor (PPAR), gerbilhttp://www.sciencedirect.com/science/article/pii/S134786131931254X |
| spellingShingle | Ravinder K. Kaundal Seethalakshmi Iyer Ashutosh Kumar Shyam S. Sharma Protective Effects of Pioglitazone Against Global Cerebral Ischemic-Reperfusion Injury in Gerbils Journal of Pharmacological Sciences |
| title | Protective Effects of Pioglitazone Against Global Cerebral Ischemic-Reperfusion Injury in Gerbils |
| title_full | Protective Effects of Pioglitazone Against Global Cerebral Ischemic-Reperfusion Injury in Gerbils |
| title_fullStr | Protective Effects of Pioglitazone Against Global Cerebral Ischemic-Reperfusion Injury in Gerbils |
| title_full_unstemmed | Protective Effects of Pioglitazone Against Global Cerebral Ischemic-Reperfusion Injury in Gerbils |
| title_short | Protective Effects of Pioglitazone Against Global Cerebral Ischemic-Reperfusion Injury in Gerbils |
| title_sort | protective effects of pioglitazone against global cerebral ischemic reperfusion injury in gerbils |
| url | http://www.sciencedirect.com/science/article/pii/S134786131931254X |
| work_keys_str_mv | AT ravinderkkaundal protectiveeffectsofpioglitazoneagainstglobalcerebralischemicreperfusioninjuryingerbils AT seethalakshmiiyer protectiveeffectsofpioglitazoneagainstglobalcerebralischemicreperfusioninjuryingerbils AT ashutoshkumar protectiveeffectsofpioglitazoneagainstglobalcerebralischemicreperfusioninjuryingerbils AT shyamssharma protectiveeffectsofpioglitazoneagainstglobalcerebralischemicreperfusioninjuryingerbils |