Dexmedetomidine pretreatment alleviates cerebral ischemia/reperfusion injury by inhibiting neuroinflammation through the JAK2/STAT3 pathway
Dexmedetomidine (DEX) is known to provide neuroprotection against cerebral ischemia and reperfusion injury (CIRI), but the exact mechanisms remain unclear. This study was conducted to investigate whether DEX pretreatment conferred neuroprotection against CIRI by inhibiting neuroinflammation through...
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Associação Brasileira de Divulgação Científica
2022-07-01
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| Series: | Brazilian Journal of Medical and Biological Research |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2022000100645&tlng=en |
| _version_ | 1811205552976429056 |
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| author | Huan Liu Jianli Li Li Jiang Jinhua He Huanhuan Zhang Keyan Wang |
| author_facet | Huan Liu Jianli Li Li Jiang Jinhua He Huanhuan Zhang Keyan Wang |
| author_sort | Huan Liu |
| collection | DOAJ |
| description | Dexmedetomidine (DEX) is known to provide neuroprotection against cerebral ischemia and reperfusion injury (CIRI), but the exact mechanisms remain unclear. This study was conducted to investigate whether DEX pretreatment conferred neuroprotection against CIRI by inhibiting neuroinflammation through the JAK2/STAT3 signaling pathway. Middle cerebral artery occlusion (MCAO) was performed to establish a cerebral ischemia/reperfusion (I/R) model. Specific-pathogen-free male Sprague-Dawley rats were randomly divided into Sham, I/R, DEX, DEX+IL-6, and AG490 (a selective inhibitor of JAK2) groups. The Longa score, TTC staining, and HE staining were used to evaluate brain damage. ELISA was used to exam levels of TNF-α. Western blotting was used to assess the levels of JAK2, phosphorylated-JAK2 (p-JAK2), STAT3, and phosphorylated-STAT3 (p-STAT3). Our results suggested that both pretreatment with DEX and AG490 decreased the Longa score and cerebral infarct areas following cerebral I/R. After treatment with IL-6, the effects of DEX on abrogating these pathological changes were reduced. HE staining revealed that I/R-induced neuronal pathological changes were attenuated by DEX application, consistent with the AG490 group. However, these effects of DEX were abolished by IL-6. Furthermore, TNF-α levels were significantly increased in the I/R group, accompanied by an increase in the levels of the p-JAK2 and p-STAT3. DEX and AG490 pretreatment down-regulated the expressions of TNF-α, p-JAK2, and p-STAT3. In contrast, the down-regulation of TNF-α, p-JAK2, and p-STAT3 induced by DEX was reversed by IL-6. Collectively, our results indicated that DEX pretreatment conferred neuroprotection against CIRI by inhibiting neuroinflammation via negatively regulating the JAK2/STAT3 signaling pathway. |
| first_indexed | 2024-04-12T03:34:29Z |
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| id | doaj.art-5a45eeefc1ef499da549989255e89607 |
| institution | Directory Open Access Journal |
| issn | 1414-431X |
| language | English |
| last_indexed | 2024-04-12T03:34:29Z |
| publishDate | 2022-07-01 |
| publisher | Associação Brasileira de Divulgação Científica |
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| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-5a45eeefc1ef499da549989255e896072022-12-22T03:49:28ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research1414-431X2022-07-015510.1590/1414-431x2022e12145Dexmedetomidine pretreatment alleviates cerebral ischemia/reperfusion injury by inhibiting neuroinflammation through the JAK2/STAT3 pathwayHuan Liuhttps://orcid.org/0000-0002-1386-740XJianli Lihttps://orcid.org/0000-0001-6867-7825Li Jianghttps://orcid.org/0000-0002-3091-3359Jinhua Hehttps://orcid.org/0000-0001-8081-2364Huanhuan Zhanghttps://orcid.org/0000-0002-1056-987XKeyan Wanghttps://orcid.org/0000-0002-1638-493XDexmedetomidine (DEX) is known to provide neuroprotection against cerebral ischemia and reperfusion injury (CIRI), but the exact mechanisms remain unclear. This study was conducted to investigate whether DEX pretreatment conferred neuroprotection against CIRI by inhibiting neuroinflammation through the JAK2/STAT3 signaling pathway. Middle cerebral artery occlusion (MCAO) was performed to establish a cerebral ischemia/reperfusion (I/R) model. Specific-pathogen-free male Sprague-Dawley rats were randomly divided into Sham, I/R, DEX, DEX+IL-6, and AG490 (a selective inhibitor of JAK2) groups. The Longa score, TTC staining, and HE staining were used to evaluate brain damage. ELISA was used to exam levels of TNF-α. Western blotting was used to assess the levels of JAK2, phosphorylated-JAK2 (p-JAK2), STAT3, and phosphorylated-STAT3 (p-STAT3). Our results suggested that both pretreatment with DEX and AG490 decreased the Longa score and cerebral infarct areas following cerebral I/R. After treatment with IL-6, the effects of DEX on abrogating these pathological changes were reduced. HE staining revealed that I/R-induced neuronal pathological changes were attenuated by DEX application, consistent with the AG490 group. However, these effects of DEX were abolished by IL-6. Furthermore, TNF-α levels were significantly increased in the I/R group, accompanied by an increase in the levels of the p-JAK2 and p-STAT3. DEX and AG490 pretreatment down-regulated the expressions of TNF-α, p-JAK2, and p-STAT3. In contrast, the down-regulation of TNF-α, p-JAK2, and p-STAT3 induced by DEX was reversed by IL-6. Collectively, our results indicated that DEX pretreatment conferred neuroprotection against CIRI by inhibiting neuroinflammation via negatively regulating the JAK2/STAT3 signaling pathway.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2022000100645&tlng=enDexmedetomidineCerebral ischemia/reperfusion injuryNeuroprotectionJAK2/STAT3 signaling pathwayInflammation |
| spellingShingle | Huan Liu Jianli Li Li Jiang Jinhua He Huanhuan Zhang Keyan Wang Dexmedetomidine pretreatment alleviates cerebral ischemia/reperfusion injury by inhibiting neuroinflammation through the JAK2/STAT3 pathway Brazilian Journal of Medical and Biological Research Dexmedetomidine Cerebral ischemia/reperfusion injury Neuroprotection JAK2/STAT3 signaling pathway Inflammation |
| title | Dexmedetomidine pretreatment alleviates cerebral ischemia/reperfusion injury by inhibiting neuroinflammation through the JAK2/STAT3 pathway |
| title_full | Dexmedetomidine pretreatment alleviates cerebral ischemia/reperfusion injury by inhibiting neuroinflammation through the JAK2/STAT3 pathway |
| title_fullStr | Dexmedetomidine pretreatment alleviates cerebral ischemia/reperfusion injury by inhibiting neuroinflammation through the JAK2/STAT3 pathway |
| title_full_unstemmed | Dexmedetomidine pretreatment alleviates cerebral ischemia/reperfusion injury by inhibiting neuroinflammation through the JAK2/STAT3 pathway |
| title_short | Dexmedetomidine pretreatment alleviates cerebral ischemia/reperfusion injury by inhibiting neuroinflammation through the JAK2/STAT3 pathway |
| title_sort | dexmedetomidine pretreatment alleviates cerebral ischemia reperfusion injury by inhibiting neuroinflammation through the jak2 stat3 pathway |
| topic | Dexmedetomidine Cerebral ischemia/reperfusion injury Neuroprotection JAK2/STAT3 signaling pathway Inflammation |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2022000100645&tlng=en |
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