PD149163 induces hypothermia to protect against brain injury in acute cerebral ischemic rats
Therapeutic hypothermia is a promising strategy for acute cerebral ischemia via physical or pharmacological methods. In this study, we pharmacologically induced hypothermia on Sprague Dawley rats by intraperitoneally injecting PD149163. We found that mild hypothermia was induced by PD149163 treatmen...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-11-01
|
| Series: | Journal of Pharmacological Sciences |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861317301731 |
| _version_ | 1811223343204925440 |
|---|---|
| author | Teng-Fei Xue Xu Ding Juan Ji Hui Yan Ji-Ye Huang Xu-Dong Guo Jin Yang Xiu-Lan Sun |
| author_facet | Teng-Fei Xue Xu Ding Juan Ji Hui Yan Ji-Ye Huang Xu-Dong Guo Jin Yang Xiu-Lan Sun |
| author_sort | Teng-Fei Xue |
| collection | DOAJ |
| description | Therapeutic hypothermia is a promising strategy for acute cerebral ischemia via physical or pharmacological methods. In this study, we pharmacologically induced hypothermia on Sprague Dawley rats by intraperitoneally injecting PD149163. We found that mild hypothermia was induced by PD149163 treatment without local cerebral blood flow (LCBF) alteration. To evaluate the neuroprotective effects of PD149163, TTC staining, HE staining and Nissl's staining were performed in our study. We found that PD149163 could prevent neuronal damage, and inhibit proliferation and activation of glial cells induced by ischemia. Simultaneously, we observed PD149163 ameliorated apoptosis characterized by down-regulated caspase-3 and Bax, but elevated Bcl-2. Moreover, PD149163 dramatically reduced JNK and AMPK/mTOR signaling pathway activation, and thereby inhibited autophagy by increased P62 expression, decreased the ratio of LC3-Ⅱ to LC3-Ⅰ and the expression of Beclin. Taken together, the present findings reveal the therapeutic effects of PD149163-induced hypothermia in brain ischemia, and provide a new strategy for stroke treatment. |
| first_indexed | 2024-04-12T08:31:15Z |
| format | Article |
| id | doaj.art-dc86bf52024e4809864860341e3b8cf3 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-04-12T08:31:15Z |
| publishDate | 2017-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-dc86bf52024e4809864860341e3b8cf32022-12-22T03:40:13ZengElsevierJournal of Pharmacological Sciences1347-86132017-11-01135310511310.1016/j.jphs.2017.10.004PD149163 induces hypothermia to protect against brain injury in acute cerebral ischemic ratsTeng-Fei Xue0Xu Ding1Juan Ji2Hui Yan3Ji-Ye Huang4Xu-Dong Guo5Jin Yang6Xiu-Lan Sun7Neuroprotective Drug Discovery Key Laboratory, Department of Pharmacology, Nanjing Medical University, 101 Longmian Road, Nanjing, Jiangsu 211166, ChinaNeuroprotective Drug Discovery Key Laboratory, Department of Pharmacology, Nanjing Medical University, 101 Longmian Road, Nanjing, Jiangsu 211166, ChinaNeuroprotective Drug Discovery Key Laboratory, Department of Pharmacology, Nanjing Medical University, 101 Longmian Road, Nanjing, Jiangsu 211166, ChinaNeuroprotective Drug Discovery Key Laboratory, Department of Pharmacology, Nanjing Medical University, 101 Longmian Road, Nanjing, Jiangsu 211166, ChinaNeuroprotective Drug Discovery Key Laboratory, Department of Pharmacology, Nanjing Medical University, 101 Longmian Road, Nanjing, Jiangsu 211166, ChinaNeuroprotective Drug Discovery Key Laboratory, Department of Pharmacology, Nanjing Medical University, 101 Longmian Road, Nanjing, Jiangsu 211166, ChinaNeuroprotective Drug Discovery Key Laboratory, Department of Pharmacology, Nanjing Medical University, 101 Longmian Road, Nanjing, Jiangsu 211166, ChinaNeuroprotective Drug Discovery Key Laboratory, Department of Pharmacology, Nanjing Medical University, 101 Longmian Road, Nanjing, Jiangsu 211166, ChinaTherapeutic hypothermia is a promising strategy for acute cerebral ischemia via physical or pharmacological methods. In this study, we pharmacologically induced hypothermia on Sprague Dawley rats by intraperitoneally injecting PD149163. We found that mild hypothermia was induced by PD149163 treatment without local cerebral blood flow (LCBF) alteration. To evaluate the neuroprotective effects of PD149163, TTC staining, HE staining and Nissl's staining were performed in our study. We found that PD149163 could prevent neuronal damage, and inhibit proliferation and activation of glial cells induced by ischemia. Simultaneously, we observed PD149163 ameliorated apoptosis characterized by down-regulated caspase-3 and Bax, but elevated Bcl-2. Moreover, PD149163 dramatically reduced JNK and AMPK/mTOR signaling pathway activation, and thereby inhibited autophagy by increased P62 expression, decreased the ratio of LC3-Ⅱ to LC3-Ⅰ and the expression of Beclin. Taken together, the present findings reveal the therapeutic effects of PD149163-induced hypothermia in brain ischemia, and provide a new strategy for stroke treatment.http://www.sciencedirect.com/science/article/pii/S1347861317301731PD149163NeurotensinHypothermiaIschemia |
| spellingShingle | Teng-Fei Xue Xu Ding Juan Ji Hui Yan Ji-Ye Huang Xu-Dong Guo Jin Yang Xiu-Lan Sun PD149163 induces hypothermia to protect against brain injury in acute cerebral ischemic rats Journal of Pharmacological Sciences PD149163 Neurotensin Hypothermia Ischemia |
| title | PD149163 induces hypothermia to protect against brain injury in acute cerebral ischemic rats |
| title_full | PD149163 induces hypothermia to protect against brain injury in acute cerebral ischemic rats |
| title_fullStr | PD149163 induces hypothermia to protect against brain injury in acute cerebral ischemic rats |
| title_full_unstemmed | PD149163 induces hypothermia to protect against brain injury in acute cerebral ischemic rats |
| title_short | PD149163 induces hypothermia to protect against brain injury in acute cerebral ischemic rats |
| title_sort | pd149163 induces hypothermia to protect against brain injury in acute cerebral ischemic rats |
| topic | PD149163 Neurotensin Hypothermia Ischemia |
| url | http://www.sciencedirect.com/science/article/pii/S1347861317301731 |
| work_keys_str_mv | AT tengfeixue pd149163induceshypothermiatoprotectagainstbraininjuryinacutecerebralischemicrats AT xuding pd149163induceshypothermiatoprotectagainstbraininjuryinacutecerebralischemicrats AT juanji pd149163induceshypothermiatoprotectagainstbraininjuryinacutecerebralischemicrats AT huiyan pd149163induceshypothermiatoprotectagainstbraininjuryinacutecerebralischemicrats AT jiyehuang pd149163induceshypothermiatoprotectagainstbraininjuryinacutecerebralischemicrats AT xudongguo pd149163induceshypothermiatoprotectagainstbraininjuryinacutecerebralischemicrats AT jinyang pd149163induceshypothermiatoprotectagainstbraininjuryinacutecerebralischemicrats AT xiulansun pd149163induceshypothermiatoprotectagainstbraininjuryinacutecerebralischemicrats |