NKG2D knockdown improves hypoxic-ischemic brain damage by inhibiting neuroinflammation in neonatal mice
Abstract Hypoxic-ischemic brain damage (HIBD) is a leading cause of neonatal death and neurological dysfunction. Neuroinflammation is identified as one of the crucial pathological mechanisms after HIBD, and natural killer group 2 member D (NKG2D) is reported to be implicated in the pathogenesis of i...
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Nature Portfolio
2024-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-52780-3 |
| _version_ | 1797276521966075904 |
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| author | Lin Liu Yuxin Yang Ting Wu Junrong Du Fangyi Long |
| author_facet | Lin Liu Yuxin Yang Ting Wu Junrong Du Fangyi Long |
| author_sort | Lin Liu |
| collection | DOAJ |
| description | Abstract Hypoxic-ischemic brain damage (HIBD) is a leading cause of neonatal death and neurological dysfunction. Neuroinflammation is identified as one of the crucial pathological mechanisms after HIBD, and natural killer group 2 member D (NKG2D) is reported to be implicated in the pathogenesis of immunoinflammatory diseases. However, the role of NKG2D in neonatal HIBD is seldomly investigated. In this study, a neonatal mice model of HIBD was induced, and the role of the NKG2D in neuroinflammation and brain injury was explored by intracerebroventricular injection of lentivirus to knockdown NKG2D in neonatal mice with HIBD. The results showed that a significant increase in NKG2D protein level in the brain of neonatal mice with HIBD. The NKG2D knockdown in the brain significantly alleviated cerebral infarction, neurobehavioral deficits, and neuronal loss in neuronal HIBD. Moreover, the neuroprotective effect of NKG2D knockdown was associated with inhibition of the activation of microglia and astrocytes, expression of NKG2D ligands (NKG2DLs) and DAP10, and the nuclear translocation of NF-κB p65. Our findings reveal NKG2D knockdown may exert anti-inflammatory and neuroprotective effects in the neonatal mice with HIBD through downregulation of NKG2D/NKG2DLs/DAP10/NF-κB pathway. These results suggest that NKG2D may be a potential target for the treatment of neonatal HIBD. |
| first_indexed | 2024-03-07T15:29:23Z |
| format | Article |
| id | doaj.art-156a2a82f24f47d3ae207c2b43a87db2 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:29:23Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-156a2a82f24f47d3ae207c2b43a87db22024-03-05T16:29:09ZengNature PortfolioScientific Reports2045-23222024-01-0114111010.1038/s41598-024-52780-3NKG2D knockdown improves hypoxic-ischemic brain damage by inhibiting neuroinflammation in neonatal miceLin Liu0Yuxin Yang1Ting Wu2Junrong Du3Fangyi Long4Department of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan UniversityDepartment of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan UniversityDepartment of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan UniversityDepartment of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan UniversityAbstract Hypoxic-ischemic brain damage (HIBD) is a leading cause of neonatal death and neurological dysfunction. Neuroinflammation is identified as one of the crucial pathological mechanisms after HIBD, and natural killer group 2 member D (NKG2D) is reported to be implicated in the pathogenesis of immunoinflammatory diseases. However, the role of NKG2D in neonatal HIBD is seldomly investigated. In this study, a neonatal mice model of HIBD was induced, and the role of the NKG2D in neuroinflammation and brain injury was explored by intracerebroventricular injection of lentivirus to knockdown NKG2D in neonatal mice with HIBD. The results showed that a significant increase in NKG2D protein level in the brain of neonatal mice with HIBD. The NKG2D knockdown in the brain significantly alleviated cerebral infarction, neurobehavioral deficits, and neuronal loss in neuronal HIBD. Moreover, the neuroprotective effect of NKG2D knockdown was associated with inhibition of the activation of microglia and astrocytes, expression of NKG2D ligands (NKG2DLs) and DAP10, and the nuclear translocation of NF-κB p65. Our findings reveal NKG2D knockdown may exert anti-inflammatory and neuroprotective effects in the neonatal mice with HIBD through downregulation of NKG2D/NKG2DLs/DAP10/NF-κB pathway. These results suggest that NKG2D may be a potential target for the treatment of neonatal HIBD.https://doi.org/10.1038/s41598-024-52780-3 |
| spellingShingle | Lin Liu Yuxin Yang Ting Wu Junrong Du Fangyi Long NKG2D knockdown improves hypoxic-ischemic brain damage by inhibiting neuroinflammation in neonatal mice Scientific Reports |
| title | NKG2D knockdown improves hypoxic-ischemic brain damage by inhibiting neuroinflammation in neonatal mice |
| title_full | NKG2D knockdown improves hypoxic-ischemic brain damage by inhibiting neuroinflammation in neonatal mice |
| title_fullStr | NKG2D knockdown improves hypoxic-ischemic brain damage by inhibiting neuroinflammation in neonatal mice |
| title_full_unstemmed | NKG2D knockdown improves hypoxic-ischemic brain damage by inhibiting neuroinflammation in neonatal mice |
| title_short | NKG2D knockdown improves hypoxic-ischemic brain damage by inhibiting neuroinflammation in neonatal mice |
| title_sort | nkg2d knockdown improves hypoxic ischemic brain damage by inhibiting neuroinflammation in neonatal mice |
| url | https://doi.org/10.1038/s41598-024-52780-3 |
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